Pub Date : 2026-03-01Epub Date: 2026-01-11DOI: 10.1016/j.bbi.2026.106274
Clara Bourgon , Laetitia Merle-Nguyen , Juliette Jacquelin , Isis Leguay , Luc Jouneau , Bernard Klonjkowski , Sophie Le Poder , Nicolas Meunier
The loss of smell has been a hallmark of the COVID-19 pandemic. Odorant detection relies on neurons present in the olfactory epithelium supported by sustentacular cells. The latter are massively infected by SARS-CoV-2 along with infiltration of innate immune cells and desquamation of the olfactory epithelium. This destruction leads to release of olfactory epithelium cells into the lumen of the nasal cavity, but the extent of the loss of mature olfactory neurons remains to be clarified. In this study, we compared the spatiotemporal evolution of the olfactory epithelium during SARS-CoV-2 infection with associated smell impairment in hamsters. The olfactory performance of infected hamsters decreases as early as 2 days post-infection (dpi), then gradually recovers through 17 dpi. While the infection is mostly resolved after 4 dpi in the nasal cavity, we observed a subacute decrease of the mature olfactory neuron population which almost completely disappear at 11 dpi. Furthermore, regeneration of the olfactory epithelium does not start until 8 dpi and leads to a high fraction of immature olfactory neurons. The delayed regeneration and persistent alteration of the olfactory neuron population was correlated with a prolonged expression of inflammatory cytokines and a rapid decrease of the levels of anti-inflammatory markers linked to regeneration. Overall, our results suggest that the regeneration process is altered in some areas of the olfactory epithelium leading to delayed recovery of the epithelium. The later may explain the prolonged smell alteration linked to SARS-CoV-2 infection.
嗅觉丧失是COVID-19大流行的一个标志。气味检测依赖于存在于嗅觉上皮中的神经元，由支撑细胞支持。后者被SARS-CoV-2大量感染，伴随着先天免疫细胞的浸润和嗅上皮的脱屑。这种破坏导致嗅觉上皮细胞释放到鼻腔腔内，但成熟嗅觉神经元损失的程度仍有待澄清。在这项研究中，我们比较了仓鼠在SARS-CoV-2感染期间嗅觉上皮的时空演变和相关的嗅觉损伤。感染仓鼠的嗅觉性能最早在感染后2 d （dpi）下降，然后在感染后17 d逐渐恢复。虽然鼻腔感染在4 dpi后基本消失，但我们观察到成熟嗅觉神经元数量亚急性减少，在11 dpi时几乎完全消失。此外，嗅觉上皮的再生直到8 dpi才开始，并导致高比例的未成熟嗅觉神经元。嗅觉神经元群的延迟再生和持续改变与炎症细胞因子的延长表达和与再生相关的抗炎标志物水平的迅速下降有关。总的来说，我们的研究结果表明，再生过程在嗅觉上皮的某些区域发生了改变，导致上皮的恢复延迟。后者可以解释与SARS-CoV-2感染有关的长期气味改变。
{"title":"Subacute loss of olfactory neurons following SARS-CoV-2 infection in hamsters","authors":"Clara Bourgon , Laetitia Merle-Nguyen , Juliette Jacquelin , Isis Leguay , Luc Jouneau , Bernard Klonjkowski , Sophie Le Poder , Nicolas Meunier","doi":"10.1016/j.bbi.2026.106274","DOIUrl":"10.1016/j.bbi.2026.106274","url":null,"abstract":"<div><div>The loss of smell has been a hallmark of the COVID-19 pandemic. Odorant detection relies on neurons present in the olfactory epithelium supported by sustentacular cells. The latter are massively infected by SARS-CoV-2 along with infiltration of innate immune cells and desquamation of the olfactory epithelium. This destruction leads to release of olfactory epithelium cells into the lumen of the nasal cavity, but the extent of the loss of mature olfactory neurons remains to be clarified. In this study, we compared the spatiotemporal evolution of the olfactory epithelium during SARS-CoV-2 infection with associated smell impairment in hamsters. The olfactory performance of infected hamsters decreases as early as 2 days post-infection (dpi), then gradually recovers through 17 dpi. While the infection is mostly resolved after 4 dpi in the nasal cavity, we observed a subacute decrease of the mature olfactory neuron population which almost completely disappear at 11 dpi. Furthermore, regeneration of the olfactory epithelium does not start until 8 dpi and leads to a high fraction of immature olfactory neurons. The delayed regeneration and persistent alteration of the olfactory neuron population was correlated with a prolonged expression of inflammatory cytokines and a rapid decrease of the levels of anti-inflammatory markers linked to regeneration. Overall, our results suggest that the regeneration process is altered in some areas of the olfactory epithelium leading to delayed recovery of the epithelium. The later may explain the prolonged smell alteration linked to SARS-CoV-2 infection.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"133 ","pages":"Article 106274"},"PeriodicalIF":7.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145965370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-01-12DOI: 10.1016/j.bbi.2026.106282
Noa van Zwieten , George Aalbers , Femke Lamers , Erik J. Giltay , Manon H.J. Hillegers , Brenda W.J.H. Penninx
Background
Daily life stress is associated with biological dysregulations including elevated inflammatory markers and poorer metabolic (immunometabolic) health, but it remains unclear how they are connected to daily life affect and behaviors. We examined whether daily life affect and behaviors were associated with immunometabolic health, and whether associations were moderated by the presence of a current depression/anxiety diagnosis.
Methods
In the Netherlands Study of Depression and Anxiety, participants (n = 357) with and without depression/anxiety self-reported positive affect (PA) and negative affect (NA) 5x/day while continuously wearing a research-grade actigraphy device for 14 days. We quantified four affect variables (i.e., M and SD of PA and NA) and three behavioral variables (i.e., minutes spent in moderate-to-vigorous physical activity [MVPA], sleep duration, and relative amplitude [RA; measure of circadian rhythmicity]), averaged across 14 days. We used linear regression analyses to explore their associations with three immunometabolic health outcomes: (1) inflammation index (based on C-Reactive Protein and Interleukin-6 levels), (2) metabolic index (based on five metabolic syndrome components), and (3) BMI (Body Mass Index), and examined if these associations were moderated by the presence of a current depression/anxiety diagnosis.
Results
Analyses showed that higher MVPA and RA were consistently associated with lower inflammation index (B = −0.19; B = −0.12), metabolic index (B = −0.14, B = −0.15), and BMI (B = −1.23; B = −1.30) (all p’s < 0.011). Longer sleep duration was associated with lower BMI (B = −0.80, p = 0.027). Affect variables were not associated with immunometabolic health outcomes (p’s > 0.05). Associations were independent of mental health status (p’s > 0.05).
Conclusions
Our findings suggest that more minutes spent in MVPA and a more pronounced circadian rhythm, assessed with actigraphy, are important correlates of better immunometabolic health, and highlight the potential of ambulatory assessment in understanding immunometabolic health.
{"title":"Daily affect and behavior in relation to inflammatory and metabolic health: An ambulatory assessment study","authors":"Noa van Zwieten , George Aalbers , Femke Lamers , Erik J. Giltay , Manon H.J. Hillegers , Brenda W.J.H. Penninx","doi":"10.1016/j.bbi.2026.106282","DOIUrl":"10.1016/j.bbi.2026.106282","url":null,"abstract":"<div><h3>Background</h3><div>Daily life stress is associated with biological dysregulations including elevated inflammatory markers and poorer metabolic (immunometabolic) health, but it remains unclear how they are connected to daily life affect and behaviors. We examined whether daily life affect and behaviors were associated with immunometabolic health, and whether associations were moderated by the presence of a current depression/anxiety diagnosis.</div></div><div><h3>Methods</h3><div>In the Netherlands Study of Depression and Anxiety, participants (n = 357) with and without depression/anxiety self-reported positive affect (PA) and negative affect (NA) 5x/day while continuously wearing a research-grade actigraphy device for 14 days. We quantified four affect variables (i.e., M and SD of PA and NA) and three behavioral variables (i.e., minutes spent in moderate-to-vigorous physical activity [MVPA], sleep duration, and relative amplitude [RA; measure of circadian rhythmicity]), averaged across 14 days. We used linear regression analyses to explore their associations with three immunometabolic health outcomes: (1) inflammation index (based on C-Reactive Protein and Interleukin-6 levels), (2) metabolic index (based on five metabolic syndrome components), and (3) BMI (Body Mass Index), and examined if these associations were moderated by the presence of a current depression/anxiety diagnosis.</div></div><div><h3>Results</h3><div>Analyses showed that higher MVPA and RA were consistently associated with lower inflammation index (B = −0.19; B = −0.12), metabolic index (B = −0.14, B = −0.15), and BMI (B = −1.23; B = −1.30) (all <em>p</em>’s < 0.011). Longer sleep duration was associated with lower BMI (B = −0.80, <em>p</em> = 0.027). Affect variables were not associated with immunometabolic health outcomes (<em>p</em>’s > 0.05). Associations were independent of mental health status (<em>p</em>’s > 0.05).</div></div><div><h3>Conclusions</h3><div>Our findings suggest that more minutes spent in MVPA and a more pronounced circadian rhythm, assessed with actigraphy, are important correlates of better immunometabolic health, and highlight the potential of ambulatory assessment in understanding immunometabolic health.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"133 ","pages":"Article 106282"},"PeriodicalIF":7.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145973932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2025-12-30DOI: 10.1016/j.bbi.2025.106252
Genevieve E. Craig , Neeti D. Mehta , Mandakh Bekhbat , Kate P. Revill , Michael J. Lucido , Changdo Hong , Evanthia C. Wommack , Wendy M. Baer , Ebrahim Haroon , Andrew H. Miller , Zhihao Li , Jennifer C. Felger
<div><div>Inflammatory biomarkers such as cytokines and C-reactive protein (CRP) are reliably elevated in patients with major depressive disorder (MDD) as well as fear and anxiety-related disorders. Moreover, inflammatory biomarkers have been associated with lower functional connectivity (FC) in reward and threat-related circuits that contribute to symptom severity. Prior work has linked low FC in reward circuitry and symptoms of anhedonia to inflammation effects on striatal dopamine (DA), including our studies involving administration of the DA precursor, levodopa (L-DOPA). Nevertheless, the mechanisms of inflammation associations with fear and anxiety-related circuits and symptoms are not fully understood. Given recent interest in DA in the amygdala in anxiety and the effects of inflammation, we examined a potential role for DA in relationships between inflammation, lower right amygdala-ventromedial prefrontal cortex (vmPFC) FC, and symptoms of anxiety and post-traumatic stress disorder (PTSD). Leveraging data from our studies in medically-stable, unmedicated adults with a primary MDD diagnosis, we tested the hypothesis that acute (250 mg; Study 1, n = 30) and sub-chronic (150–450 mg/day/week; Study 2, n = 18) L-DOPA (administered with carbidopa) versus placebo would increase right amygdala-vmPFC resting state (rs)FC (using a targeted, <em>a priori</em> approach) in patients with higher (but not lower) inflammation, in relation to comorbid anxiety and PTSD symptoms. In patients enrolled to have a range of CRP concentrations and rsFC before and after acute, within-subject challenge with both L-DOPA and placebo (double-blind, randomized order ∼ 1-week apart; Study 1), a CRP by treatment interaction (F[1,28] = 1.33, p < 0.05) revealed that right amygdala-vmPFC rsFC was increased by L-DOPA versus placebo only in patients with CRP > versus ≤ 2 mg/L (p < 0.05). In MDD patients recruited to have CRP > 2 mg/L in Study 2, L-DOPA increased right amygdala-vmPFC rsFC versus placebo (F[1,12] = 9.24, p < 0.05), with two of three L-DOPA doses (150 and 450 mg/day) increasing rsFC versus placebo at a predetermined threshold of ≥ 20 %. Repeated L-DOPA versus placebo further decreased self-reported anxiety symptoms and state anxiety (F[2,16] = 11.87, p < 0.01), with all three L-DOPA doses significantly decreasing state anxiety (p < 0.05). Right amygdala-vmPFC rsFC responses to L-DOPA also associated with greater reductions in state anxiety (r = -0.72, p < 0.05). Similarly, L-DOPA decreased PTSD symptom severity versus placebo across all four PTSD symptom clusters (B-E) in patients with significant PTSD symptoms at baseline (n = 11; all p < 0.05), with right amygdala-vmPFC rsFC responses to L-DOPA versus placebo negatively correlating with improved Intrusion symptoms (r = -0.81, p < 0.05). These findings suggest a role for DA in the effects of inflammation on fear and anxiety-related circuits and symptoms, while supporting the use of
{"title":"Effects of Dopaminergic Therapy with Levodopa (L-DOPA) on Fear and Anxiety-Related Circuits and Symptoms in Patients with Depression and Higher Inflammation","authors":"Genevieve E. Craig , Neeti D. Mehta , Mandakh Bekhbat , Kate P. Revill , Michael J. Lucido , Changdo Hong , Evanthia C. Wommack , Wendy M. Baer , Ebrahim Haroon , Andrew H. Miller , Zhihao Li , Jennifer C. Felger","doi":"10.1016/j.bbi.2025.106252","DOIUrl":"10.1016/j.bbi.2025.106252","url":null,"abstract":"<div><div>Inflammatory biomarkers such as cytokines and C-reactive protein (CRP) are reliably elevated in patients with major depressive disorder (MDD) as well as fear and anxiety-related disorders. Moreover, inflammatory biomarkers have been associated with lower functional connectivity (FC) in reward and threat-related circuits that contribute to symptom severity. Prior work has linked low FC in reward circuitry and symptoms of anhedonia to inflammation effects on striatal dopamine (DA), including our studies involving administration of the DA precursor, levodopa (L-DOPA). Nevertheless, the mechanisms of inflammation associations with fear and anxiety-related circuits and symptoms are not fully understood. Given recent interest in DA in the amygdala in anxiety and the effects of inflammation, we examined a potential role for DA in relationships between inflammation, lower right amygdala-ventromedial prefrontal cortex (vmPFC) FC, and symptoms of anxiety and post-traumatic stress disorder (PTSD). Leveraging data from our studies in medically-stable, unmedicated adults with a primary MDD diagnosis, we tested the hypothesis that acute (250 mg; Study 1, n = 30) and sub-chronic (150–450 mg/day/week; Study 2, n = 18) L-DOPA (administered with carbidopa) versus placebo would increase right amygdala-vmPFC resting state (rs)FC (using a targeted, <em>a priori</em> approach) in patients with higher (but not lower) inflammation, in relation to comorbid anxiety and PTSD symptoms. In patients enrolled to have a range of CRP concentrations and rsFC before and after acute, within-subject challenge with both L-DOPA and placebo (double-blind, randomized order ∼ 1-week apart; Study 1), a CRP by treatment interaction (F[1,28] = 1.33, p < 0.05) revealed that right amygdala-vmPFC rsFC was increased by L-DOPA versus placebo only in patients with CRP > versus ≤ 2 mg/L (p < 0.05). In MDD patients recruited to have CRP > 2 mg/L in Study 2, L-DOPA increased right amygdala-vmPFC rsFC versus placebo (F[1,12] = 9.24, p < 0.05), with two of three L-DOPA doses (150 and 450 mg/day) increasing rsFC versus placebo at a predetermined threshold of ≥ 20 %. Repeated L-DOPA versus placebo further decreased self-reported anxiety symptoms and state anxiety (F[2,16] = 11.87, p < 0.01), with all three L-DOPA doses significantly decreasing state anxiety (p < 0.05). Right amygdala-vmPFC rsFC responses to L-DOPA also associated with greater reductions in state anxiety (r = -0.72, p < 0.05). Similarly, L-DOPA decreased PTSD symptom severity versus placebo across all four PTSD symptom clusters (B-E) in patients with significant PTSD symptoms at baseline (n = 11; all p < 0.05), with right amygdala-vmPFC rsFC responses to L-DOPA versus placebo negatively correlating with improved Intrusion symptoms (r = -0.81, p < 0.05). These findings suggest a role for DA in the effects of inflammation on fear and anxiety-related circuits and symptoms, while supporting the use of ","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"133 ","pages":"Article 106252"},"PeriodicalIF":7.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-03DOI: 10.1016/j.bbi.2025.106208
Jie Liu, Zheng Li, Xiaoling Peng, Wei Zhao, Tiantian Chu, Jie Ju, Jihao Ren, Feng Gao
Chronic neuropathic pain is frequently accompanied by cognitive impairment, which seriously influence the quality of the patient’s life. The stability of synapse is the basis for maintaining neural circuits. And overactive microglia can prune normal synapses through phagocytosis, leading to cognitive impairment. This study aims to investigate the role of microglial synaptic pruning in chronic neuropathic pain-induced cognitive impairment, and explore the mechanisms of microglial activation through Interleukin-17A (IL-17A) activation and copper accumulation. We found that chronic neuropathic pain resulted in cognitive impairment, and microglial activation, abnormal microglial synaptic pruning, synaptic loss in hippocampus. Depleting microglia ameliorated the activations of microglial and complement pathways, and rescued synaptic loss and cognitive impairment. The copper was accumulated in hippocampus, and copper chelator tetrathiomolybdate (TTM) inhibited microglial and complement activations and rescued synaptic loss and cognitive impairment. Further research found that suppressing mitochondrial oxidative stress response inhibited copper accumulation-induced microglial activation. Finally, IL-17A was found to be increased in serum and hippocampus. IL-17A neutralization antibody (anti-IL-17A Abs) alleviated copper accumulation by inhibiting six transmembrane epithelial antigens of prostate 4 (STEAP4) / copper transporter 1 (CTR1), and inhibited microglial and complement activation, interrupting abnormal synaptic elimination and ameliorating cognitive impairment. Our results suggest that IL-17A can induce copper accumulation in microglia through STEAP4/CTR1, the latter promotes complement-mediated microglia synaptic pruning, reducing synapse number, and ultimately resulting in cognitive impairment. These provide a new potential therapeutic target for the treatment of chronic neuropathic pain-induced cognitive impairment.
{"title":"IL-17A-mediated copper accumulation participates in chronic neuropathic pain-induced cognitive impairment by enhancing microglial synaptic pruning","authors":"Jie Liu, Zheng Li, Xiaoling Peng, Wei Zhao, Tiantian Chu, Jie Ju, Jihao Ren, Feng Gao","doi":"10.1016/j.bbi.2025.106208","DOIUrl":"10.1016/j.bbi.2025.106208","url":null,"abstract":"<div><div>Chronic neuropathic pain is frequently accompanied by cognitive impairment, which seriously influence the quality of the patient’s life. The stability of synapse is the basis for maintaining neural circuits. And overactive microglia can prune normal synapses through phagocytosis, leading to cognitive impairment. This study aims to investigate the role of microglial synaptic pruning in chronic neuropathic pain-induced cognitive impairment, and explore the mechanisms of microglial activation through Interleukin-17A (IL-17A) activation and copper accumulation. We found that chronic neuropathic pain resulted in cognitive impairment, and microglial activation, abnormal microglial synaptic pruning, synaptic loss in hippocampus. Depleting microglia ameliorated the activations of microglial and complement pathways, and rescued synaptic loss and cognitive impairment. The copper was accumulated in hippocampus, and copper chelator tetrathiomolybdate (TTM) inhibited microglial and complement activations and rescued synaptic loss and cognitive impairment. Further research found that suppressing mitochondrial oxidative stress response inhibited copper accumulation-induced microglial activation. Finally, IL-17A was found to be increased in serum and hippocampus. IL-17A neutralization antibody (anti-IL-17A Abs) alleviated copper accumulation by inhibiting six transmembrane epithelial antigens of prostate 4 (STEAP4) / copper transporter 1 (CTR1), and inhibited microglial and complement activation, interrupting abnormal synaptic elimination and ameliorating cognitive impairment. Our results suggest that IL-17A can induce copper accumulation in microglia through STEAP4/CTR1, the latter promotes complement-mediated microglia synaptic pruning, reducing synapse number, and ultimately resulting in cognitive impairment. These provide a new potential therapeutic target for the treatment of chronic neuropathic pain-induced cognitive impairment.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"132 ","pages":"Article 106208"},"PeriodicalIF":7.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145687030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-18DOI: 10.1016/j.bbi.2025.106225
Saül Pascual-Diaz , Maria Suñol , Marie-Eve Hoeppli , Emma Biggs , Christopher D. King , Nima Aghaeepour , Martin S. Angst , Edward Ganio , Amelie Cambriel , Dorien Feyaerts , Brice Gaudilliere , Jennifer N. Stinson , Massieh Moayedi , Robert C. Coghill , Laura E. Simons , Marina López-Solà
Chronic musculoskeletal (MSK) pain affects a substantial proportion of youth, with 5 % reporting high-impact symptoms. Chronic pain in youth leads to multifaceted negative consequences that profoundly affect adolescents’ quality of life (QoL) and future outcomes. Recent studies suggest that neuro-immune interactions significantly contribute to chronic pain. However, how systemic immune dysregulation influences brain function, and how these brain changes affect well-being and functioning in chronic pain remains unclear. This study aims to examine the convergence between immune function and brain processing during a multisensory task to identify novel mechanistic pathways that may explain reduced QoL in adolescents with chronic MSK pain (N = 129). We used a multisensory fMRI task designed to mimic the unpleasant sensory experiences that adolescents and adults with chronic pain often encounter in daily life. Higher task-evoked activation in the rostral anterior cingulate and dorsomedial prefrontal cortices (rACC–dmPFC), which support threat appraisal and response regulation, was associated with lower physical QoL (pFWE = 0.005). Lower physical QoL was also associated with augmented functional connectivity between the rACC-dmPFC region and sensory processing areas in the somatosensory (pFWE = 0.002) and visual (pFWE = 0.049) cortices. Higher systemic pro-inflammatory activity in immature neutrophils was also associated with lower physical QoL (p = 0.01). Furthermore, task-evoked brain activation in the rACC-dmPFC partially mediated the relationship between neutrophil-mediated inflammatory responses and reduced physical QoL. These findings suggest a potential neuro-immune pathway through which systemic immune alterations may affect brain function and QoL in adolescents with chronic MSK pain.
{"title":"Brain-immune correlates of quality of life in adolescents with chronic musculoskeletal pain","authors":"Saül Pascual-Diaz , Maria Suñol , Marie-Eve Hoeppli , Emma Biggs , Christopher D. King , Nima Aghaeepour , Martin S. Angst , Edward Ganio , Amelie Cambriel , Dorien Feyaerts , Brice Gaudilliere , Jennifer N. Stinson , Massieh Moayedi , Robert C. Coghill , Laura E. Simons , Marina López-Solà","doi":"10.1016/j.bbi.2025.106225","DOIUrl":"10.1016/j.bbi.2025.106225","url":null,"abstract":"<div><div>Chronic musculoskeletal (MSK) pain affects a substantial proportion of youth, with 5 % reporting high-impact symptoms. Chronic pain in youth leads to multifaceted negative consequences that profoundly affect adolescents’ quality of life (QoL) and future outcomes. Recent studies suggest that neuro-immune interactions significantly contribute to chronic pain. However, how systemic immune dysregulation influences brain function, and how these brain changes affect well-being and functioning in chronic pain remains unclear. This study aims to examine the convergence between immune function and brain processing during a multisensory task to identify novel mechanistic pathways that may explain reduced QoL in adolescents with chronic MSK pain (N = 129). We used a multisensory fMRI task designed to mimic the unpleasant sensory experiences that adolescents and adults with chronic pain often encounter in daily life. Higher task-evoked activation in the rostral anterior cingulate and dorsomedial prefrontal cortices (rACC–dmPFC), which support threat appraisal and response regulation, was associated with lower physical QoL (pFWE = 0.005). Lower physical QoL was also associated with augmented functional connectivity between the rACC-dmPFC region and sensory processing areas in the somatosensory (pFWE = 0.002) and visual (pFWE = 0.049) cortices. Higher systemic pro-inflammatory activity in immature neutrophils was also associated with lower physical QoL (p = 0.01). Furthermore, task-evoked brain activation in the rACC-dmPFC partially mediated the relationship between neutrophil-mediated inflammatory responses and reduced physical QoL. These findings suggest a potential neuro-immune pathway through which systemic immune alterations may affect brain function and QoL in adolescents with chronic MSK pain.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"132 ","pages":"Article 106225"},"PeriodicalIF":7.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145797426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-09DOI: 10.1016/j.bbi.2025.106214
Wiesława Florek , Katarzyna Barłowska , Marta Marlena Ziętek , Rafał Radosław Starzyński , Pasqualino Loi , Silvestre Sampino
Neurodevelopmental disorders (ND) arise from a complex interaction between genetic and maternal environmental factors occurring during pregnancy and involving the immune system. Rodent models, particularly genetic and immune-based approaches, have significantly advanced our understanding of ND etiology and pathogenesis. However, translationally relevant large animal model of maternal immune activation, capable of recapitulating behavioral phenotypes and biomarker associations consistent with ND are missing. In this study, we aimed to model ND in sheep by inducing Maternal Immune Activation (MIA) in pregnant ewes, as prenatal infections are well-replicated environmental factors associated with an increased risk of ND in humans. Pregnant ewes were challenged with bacterial lipopolysaccharide (LPS) to induce MIA at either mid- or late pregnancy, and the lambs’ behaviors were monitored after birth. Moreover, we developed and validated a battery of behavioral assays (e.g., Isolation Test, V-Detour Test, and T-Maze) to assess ND-related behavioral domains in lambs, such as social attachment, spatial learning, inhibitory control, and cognitive flexibility. Lambs prenatally exposed to MIA exhibited selective impairments in cognitive domains, including learning, memory consolidation, and cognitive flexibility, while developmental milestones and core social behaviors, such as maternal bonding, remained unchanged. Importantly, individual differences in maternal inflammatory responses, particularly IL-6 levels, correlated with the severity of behavioral alterations in the offspring. The observed behavioral phenotypes and immunological correlations support the validity of the ovine model for studying ND and related behavioral disorders. Our findings lay the groundwork for using sheep in future mechanistic and preclinical research on neurodevelopmental disorders.
{"title":"The sheep as a translational model for neurodevelopmental disorders induced by prenatal maternal immune activation","authors":"Wiesława Florek , Katarzyna Barłowska , Marta Marlena Ziętek , Rafał Radosław Starzyński , Pasqualino Loi , Silvestre Sampino","doi":"10.1016/j.bbi.2025.106214","DOIUrl":"10.1016/j.bbi.2025.106214","url":null,"abstract":"<div><div>Neurodevelopmental disorders (ND) arise from a complex interaction between genetic and maternal environmental factors occurring during pregnancy and involving the immune system. Rodent models, particularly genetic and immune-based approaches, have significantly advanced our understanding of ND etiology and pathogenesis. However, translationally relevant large animal model of maternal immune activation, capable of recapitulating behavioral phenotypes and biomarker associations consistent with ND are missing. In this study, we aimed to model ND in sheep by inducing Maternal Immune Activation (MIA) in pregnant ewes, as prenatal infections are well-replicated environmental factors associated with an increased risk of ND in humans. Pregnant ewes were challenged with bacterial lipopolysaccharide (LPS) to induce MIA at either mid- or late pregnancy, and the lambs’ behaviors were monitored after birth. Moreover, we developed and validated a battery of behavioral assays (e.g., Isolation Test, V-Detour Test, and T-Maze) to assess ND-related behavioral domains in lambs, such as social attachment, spatial learning, inhibitory control, and cognitive flexibility. Lambs prenatally exposed to MIA exhibited selective impairments in cognitive domains, including learning, memory consolidation, and cognitive flexibility, while developmental milestones and core social behaviors, such as maternal bonding, remained unchanged. Importantly, individual differences in maternal inflammatory responses, particularly IL-6 levels, correlated with the severity of behavioral alterations in the offspring. The observed behavioral phenotypes and immunological correlations support the validity of the ovine model for studying ND and related behavioral disorders. Our findings lay the groundwork for using sheep in future mechanistic and preclinical research on neurodevelopmental disorders.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"132 ","pages":"Article 106214"},"PeriodicalIF":7.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145741127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-19DOI: 10.1016/j.bbi.2025.106230
Gabrielle R. Rinne , Christine Dunkel Schetter , Susan Jackman , Steve W. Cole
The in-utero environment shapes offspring mental and physical health trajectories over the lifespan, likely through developmental adaptations to fetal biological systems. Offspring immune system development is a putative pathway through which the prenatal environment influences offspring health. The current study tested associations of maternal prenatal depressive and anxiety symptoms with infant pro-inflammatory and antiviral gene expression in a sample of 118 mother-infant pairs enrolled in a longitudinal study. Mothers reported on depressive and anxiety symptoms during interviews in early, mid, and late pregnancy. About one month after birth, trained research staff collected dried blood spots from infants during a heel stick procedure (M = 1.3 months, SD = 1.1 months). Infant dried blood spots were assayed for genome-wide transcriptional profiles using RNAseq. We evaluated associations of maternal prenatal depressive and anxiety symptoms with infant genome-wide transcriptional profiles and used bioinformatics analyses to identify upstream transcriptional pathways of differentially expressed genes. Higher maternal depressive symptom levels over the course of pregnancy were associated with upregulation of the pro-inflammatory NF-κB transcription control pathway and downregulation of the antiviral IRF control pathway in infants. In contrast, anxiety symptoms were associated with downregulation of the antiviral transcriptional control pathway in infants but were not associated with differences in the pro-inflammatory transcriptional control pathway. However, the association of anxiety symptoms with antiviral transcriptional control pathways was no longer significant with adjustment for depressive symptoms. These findings suggest that depressive symptoms during pregnancy may influence infant immune function via inflammatory and antiviral transcriptional control pathways, with potential implications for subsequent health.
{"title":"Developmental origins of immune function: Maternal prenatal mood is associated with infant immune cell gene expression","authors":"Gabrielle R. Rinne , Christine Dunkel Schetter , Susan Jackman , Steve W. Cole","doi":"10.1016/j.bbi.2025.106230","DOIUrl":"10.1016/j.bbi.2025.106230","url":null,"abstract":"<div><div>The in-utero environment shapes offspring mental and physical health trajectories over the lifespan, likely through developmental adaptations to fetal biological systems. Offspring immune system development is a putative pathway through which the prenatal environment influences offspring health. The current study tested associations of maternal prenatal depressive and anxiety symptoms with infant pro-inflammatory and antiviral gene expression in a sample of 118 mother-infant pairs enrolled in a longitudinal study. Mothers reported on depressive and anxiety symptoms during interviews in early, mid, and late pregnancy. About one month after birth, trained research staff collected dried blood spots from infants during a heel stick procedure (<em>M</em> = 1.3 months, <em>SD</em> = 1.1 months). Infant dried blood spots were assayed for genome-wide transcriptional profiles using RNAseq. We evaluated associations of maternal prenatal depressive and anxiety symptoms with infant genome-wide transcriptional profiles and used bioinformatics analyses to identify upstream transcriptional pathways of differentially expressed genes. Higher maternal depressive symptom levels over the course of pregnancy were associated with upregulation of the pro-inflammatory NF-κB transcription control pathway and downregulation of the antiviral IRF control pathway in infants. In contrast, anxiety symptoms were associated with downregulation of the antiviral transcriptional control pathway in infants but were not associated with differences in the pro-inflammatory transcriptional control pathway. However, the association of anxiety symptoms with antiviral transcriptional control pathways was no longer significant with adjustment for depressive symptoms. These findings suggest that depressive symptoms during pregnancy may influence infant immune function via inflammatory and antiviral transcriptional control pathways, with potential implications for subsequent health.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"132 ","pages":"Article 106230"},"PeriodicalIF":7.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145803186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-11DOI: 10.1016/j.bbi.2025.106217
Viacheslav A. Petrov , Sebastian Schade , Cedric C. Laczny , Jenny Hällqvist , Patrick May , Christian Jäger , Velma T.E. Aho , Oskar Hickl , Rashi Halder , Elisabeth Lang , Jordan Caussin , Laura A. Lebrun , Janine Schulz , Marcus Michael Unger , Kevin Mills , Brit Mollenhauer , Paul Wilmes
Alterations in the gut microbiome and a “leaky” gut are associated with Parkinson’s disease (PD), which implies the prospect of rebalancing via dietary intervention. Here, we investigate the impact of a diet rich in resistant starch on the gut microbiome through a multi-omics approach. We conducted a randomized, controlled trial with short-term and long-term phases involving 74 PD patients of three groups: conventional diet, supplementation with resistant starch, and high-fibre diet.
Our findings reveal associations between dietary patterns and changes in the gut microbiome’s taxonomic composition, functional potential, metabolic activity, and host inflammatory proteome response. Resistant starch supplementation led to an increase in Faecalibacterium species and short-chain fatty acids alongside a reduction in opportunistic pathogens. Long-term supplementation also increased blood APOA4 and HSPA5 and reduced symptoms of PD.
Our study highlights the potential of dietary interventions to modulate the gut microbiome and improve the quality of life for PD patients.
{"title":"Resistant starch improves Parkinson’s disease symptoms through restructuring of the gut microbiome and modulating inflammation","authors":"Viacheslav A. Petrov , Sebastian Schade , Cedric C. Laczny , Jenny Hällqvist , Patrick May , Christian Jäger , Velma T.E. Aho , Oskar Hickl , Rashi Halder , Elisabeth Lang , Jordan Caussin , Laura A. Lebrun , Janine Schulz , Marcus Michael Unger , Kevin Mills , Brit Mollenhauer , Paul Wilmes","doi":"10.1016/j.bbi.2025.106217","DOIUrl":"10.1016/j.bbi.2025.106217","url":null,"abstract":"<div><div>Alterations in the gut microbiome and a “leaky” gut are associated with Parkinson’s disease (PD), which implies the prospect of rebalancing via dietary intervention. Here, we investigate the impact of a diet rich in resistant starch on the gut microbiome through a multi-omics approach. We conducted a randomized, controlled trial with short-term and long-term phases involving 74 PD patients of three groups: conventional diet, supplementation with resistant starch, and high-fibre diet.</div><div>Our findings reveal associations between dietary patterns and changes in the gut microbiome’s taxonomic composition, functional potential, metabolic activity, and host inflammatory proteome response. Resistant starch supplementation led to an increase in <em>Faecalibacterium</em> species and short-chain fatty acids alongside a reduction in opportunistic pathogens. Long-term supplementation also increased blood APOA4 and HSPA5 and reduced symptoms of PD.</div><div>Our study highlights the potential of dietary interventions to modulate the gut microbiome and improve the quality of life for PD patients.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"132 ","pages":"Article 106217"},"PeriodicalIF":7.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145751664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-20DOI: 10.1016/j.bbi.2025.106232
Ellen Jopling , Avril Metcalfe-Roach , Stuart E. Turvey , Piushkumar Mandhane , the CHILD Study investigators , B. Brett Finlay , Joelle LeMoult
Elevated stress during the prenatal period is associated with increased psychiatric risk among children. However, less is known about the mechanisms through which this intergenerational transmission of risk occurs. The early life microbiome is one candidate mechanism through which maternal stress during the prenatal period could impact offspring mental health, with a growing body of literature highlighting the importance of the early life microbiome in mental health across the lifespan. This study leverages Canada’s largest deeply phenotyped birth cohort to elucidate the mechanistic associations between maternal prenatal stress, dynamic changes in the microbiome across the first year of life, and child internalizing symptoms. Analytic sample size with use of full information maximum likelihood methodology was 2,985. Analyses indicated that early diversification of the early life microbiome significantly mediated the relation between higher maternal perceived stress during pregnancy and increased internalizing symptoms among offspring at 5 years of age. Crucially, microbial taxa impacted by early diversification of the microbiome implicated the immune system. This work supports maturational dynamics of the microbiome as one mechanism through which prenatal stress is biologically embedded to impact offspring’s later mental health. By linking several burgeoning areas of research, this study lays the groundwork for future multidisciplinary work examining the intergenerational transmission of psychiatric risk through the microbiome.
{"title":"The infant gut microbiome and the intergenerational transmission of psychiatric risk","authors":"Ellen Jopling , Avril Metcalfe-Roach , Stuart E. Turvey , Piushkumar Mandhane , the CHILD Study investigators , B. Brett Finlay , Joelle LeMoult","doi":"10.1016/j.bbi.2025.106232","DOIUrl":"10.1016/j.bbi.2025.106232","url":null,"abstract":"<div><div>Elevated stress during the prenatal period is associated with increased psychiatric risk among children. However, less is known about the mechanisms through which this intergenerational transmission of risk occurs. The early life microbiome is one candidate mechanism through which maternal stress during the prenatal period could impact offspring mental health, with a growing body of literature highlighting the importance of the early life microbiome in mental health across the lifespan. This study leverages Canada’s largest deeply phenotyped birth cohort to elucidate the mechanistic associations between maternal prenatal stress, dynamic changes in the microbiome across the first year of life, and child internalizing symptoms. Analytic sample size with use of full information maximum likelihood methodology was 2,985. Analyses indicated that early diversification of the early life microbiome significantly mediated the relation between higher maternal perceived stress during pregnancy and increased internalizing symptoms among offspring at 5 years of age. Crucially, microbial taxa impacted by early diversification of the microbiome implicated the immune system. This work supports maturational dynamics of the microbiome as one mechanism through which prenatal stress is biologically embedded to impact offspring’s later mental health. By linking several burgeoning areas of research, this study lays the groundwork for future multidisciplinary work examining the intergenerational transmission of psychiatric risk through the microbiome.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"132 ","pages":"Article 106232"},"PeriodicalIF":7.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145809642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-17DOI: 10.1016/j.bbi.2025.106222
Maria Elisa Caetano-Silva , Miranda E. Hilt , Ivan Valishev , Casey Lim , Mikaela Kasperek , Akriti Shrestha , Helen Fu , Eleanor Eck , Robert McCusker , Heather Armstrong , Brett Loman , Michael T. Bailey , Jacob M. Allen
Psychological stress is a known risk factor for inflammatory bowel disease (IBD), but the mechanisms linking stress to worsened disease remain unclear. Because distinct stress paradigms activate different neuroimmune circuits, it is critical to investigate model-specific effects. We examined how social stress primes the gut for heightened inflammation and whether this is mediated by specific neuroendocrine pathways, including α2-/β-adrenergic (sympathetic) or glucocorticoid/ corticotropin-releasing hormone receptor (CRHR1) (HPA axis) signaling. Mice were exposed to social disruption (SDR) stress and pre-treated with pharmacological antagonists targeting α2-adrenergic receptors (idazoxan), β-adrenergic receptor (β-AR) (propranolol), glucocorticoid receptor (mifepristone), or CRHR1 (antalarmin). Intestinal epithelial cell (IEC) gene expression and microbiota composition were assessed following SDR. To determine disease impact, SDR was combined with either Citrobacter rodentium infection or dextran sulfate sodium (DSS)-induced colitis, with interventions including the β-AR inhibitors and the NADPH oxidase inhibitor apocynin. SDR significantly upregulated expression of Dual oxidase 2 (Duox2), Dual oxidase maturation factor 2 (Duoxa2), and inducible nitric oxide synthase 2 (Nos2) in IECs (2- to 8-fold, p < 0.0001), effects reversed by β-AR blockade but not α2-adrenergic, CRH, or glucocorticoid inhibition. SDR also induced microbial dysbiosis, characterized by reduced α −diversity and compositional shifts, which was rescued by propranolol. Stress exacerbated disease severity in both infectious (C. rodentium) and chemically induced (DSS) colitis, amplifying colonic expression of Duox2, Nos2, and Ccl2, especially. Apocynin mitigated stress-induced ROS/RNS production and body weight loss even prior to colitis onset, reduced colonic expression of key oxidative enzymes, especially DUOX2, and alleviated both chemically and infectious colitis severity. These findings provide strong evidence that social stress sensitizes the gut to inflammation through β-adrenergic and NADPH oxidase–driven oxidative stress, highlighting potential therapeutic targets for mitigating stress-exacerbated IBD.
{"title":"Social stress worsens colitis through β-adrenergic–driven oxidative stress in intestinal mucosal compartments","authors":"Maria Elisa Caetano-Silva , Miranda E. Hilt , Ivan Valishev , Casey Lim , Mikaela Kasperek , Akriti Shrestha , Helen Fu , Eleanor Eck , Robert McCusker , Heather Armstrong , Brett Loman , Michael T. Bailey , Jacob M. Allen","doi":"10.1016/j.bbi.2025.106222","DOIUrl":"10.1016/j.bbi.2025.106222","url":null,"abstract":"<div><div>Psychological stress is a known risk factor for inflammatory bowel disease (IBD), but the mechanisms linking stress to worsened disease remain unclear. Because distinct stress paradigms activate different neuroimmune circuits, it is critical to investigate model-specific effects. We examined how social stress primes the gut for heightened inflammation and whether this is mediated by specific neuroendocrine pathways, including α2-/β-adrenergic (sympathetic) or glucocorticoid/ corticotropin-releasing hormone receptor (CRHR1) (HPA axis) signaling. Mice were exposed to social disruption (SDR) stress and pre-treated with pharmacological antagonists targeting α2-adrenergic receptors (idazoxan), β-adrenergic receptor (β-AR) (propranolol), glucocorticoid receptor (mifepristone), or CRHR1 (antalarmin). Intestinal epithelial cell (IEC) gene expression and microbiota composition were assessed following SDR. To determine disease impact, SDR was combined with either <em>Citrobacter rodentium</em> infection or dextran sulfate sodium (DSS)-induced colitis, with interventions including the β-AR inhibitors and the NADPH oxidase inhibitor apocynin. SDR significantly upregulated expression of Dual oxidase 2 (<em>Duox2</em>), Dual oxidase maturation factor 2 (<em>Duoxa2</em>), and inducible nitric oxide synthase 2 (<em>Nos2</em>) in IECs (2- to 8-fold, <em>p</em> < 0.0001), effects reversed by β-AR blockade but not α2-adrenergic, CRH, or glucocorticoid inhibition. SDR also induced microbial dysbiosis, characterized by reduced α −diversity and compositional shifts, which was rescued by propranolol. Stress exacerbated disease severity in both infectious (<em>C. rodentium</em>) and chemically induced (DSS) colitis, amplifying colonic expression of <em>Duox2</em>, <em>Nos2</em>, and <em>Ccl2</em>, especially. Apocynin mitigated stress-induced ROS/RNS production and body weight loss even prior to colitis onset, reduced colonic expression of key oxidative enzymes, especially DUOX2, and alleviated both chemically and infectious colitis severity. These findings provide strong evidence that social stress sensitizes the gut to inflammation through β-adrenergic and NADPH oxidase–driven oxidative stress, highlighting potential therapeutic targets for mitigating stress-exacerbated IBD.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"132 ","pages":"Article 106222"},"PeriodicalIF":7.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145793402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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