The occurrence and development of amyotrophic lateral sclerosis (ALS) involve neuroinflammatory responses, in which microglial activation plays a critical role. IRF5, a key regulator of inflammatory responses, is implicated in the disease mechanisms of various conditions. However, its mechanism in ALS remains unclear. This study found that IRF5 expression was significantly increased in hSOD1-G93A transgenic ALS mice and cell models, primarily localized in activated microglia. Silencing IRF5 altered microglial polarization, suppressed the release of inflammatory factors, enhanced phagocytic function, and reduced motor neuron apoptosis in a co-culture system. Mechanistic studies suggested that IRF5 may regulate microglial function through the NF-κB signaling pathway. This study reveals the key role of IRF5 in microglia-mediated neuroinflammation and neuronal damage in ALS, indicating that targeting IRF5 could represent a promising treatment strategy for this disease.
{"title":"The role of IRF5 in Microglia-Mediated neuroinflammation in ALS.","authors":"Lu Yang, Wenyuan Fan, Zuhuan Wang, Minhua Wu, Yanchun Chen, Jitai Cheng, Fenghua Zhou, Zhangyu Guo","doi":"10.1016/j.neulet.2026.138580","DOIUrl":"10.1016/j.neulet.2026.138580","url":null,"abstract":"<p><p>The occurrence and development of amyotrophic lateral sclerosis (ALS) involve neuroinflammatory responses, in which microglial activation plays a critical role. IRF5, a key regulator of inflammatory responses, is implicated in the disease mechanisms of various conditions. However, its mechanism in ALS remains unclear. This study found that IRF5 expression was significantly increased in hSOD1-G93A transgenic ALS mice and cell models, primarily localized in activated microglia. Silencing IRF5 altered microglial polarization, suppressed the release of inflammatory factors, enhanced phagocytic function, and reduced motor neuron apoptosis in a co-culture system. Mechanistic studies suggested that IRF5 may regulate microglial function through the NF-κB signaling pathway. This study reveals the key role of IRF5 in microglia-mediated neuroinflammation and neuronal damage in ALS, indicating that targeting IRF5 could represent a promising treatment strategy for this disease.</p>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":" ","pages":"138580"},"PeriodicalIF":2.0,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147474484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-15DOI: 10.1016/j.neulet.2026.138579
Zubin Singh Rana, Pradeep Punnakkal
Dorsal root ganglion (DRG) neurons serve as the first-order sensory neurons relaying peripheral inputs to the spinal cord. Studies have shown that dopaminergic signalling contributes to the modulation of DRG neurons excitability and nociceptive transmission. In this study, we examined the effects of dopamine receptor subtypes on the excitability of small and large-sized DRG neurons using whole-cell patch-clamp recordings in acutely cultured rat DRG neurons. Activation of D1-like receptors by SKF38393 caused a depolarizing shift in the action potential threshold in small sized DRG neurons whereas an increase in spike width was observed in both small and large sized DRG neurons, suggesting reduced excitability likely mediated through modulation of sodium channel activity, whereas activation of D2-like receptors by ropinirole reduced the action potential amplitude and modulated the repolarization dynamics in small sized DRG neurons, indicating potential involvement of Gi-coupled mechanisms affecting sodium and potassium currents. Together, these findings demonstrate subtype-specific modulation of DRG neurons excitability by dopamine and highlight the peripheral dopaminergic system as a critical regulator of nociceptive signalling with potential implications for pain management.
{"title":"Dopamine receptor subtypes modulate the excitability of dorsal root ganglion neurons.","authors":"Zubin Singh Rana, Pradeep Punnakkal","doi":"10.1016/j.neulet.2026.138579","DOIUrl":"10.1016/j.neulet.2026.138579","url":null,"abstract":"<p><p>Dorsal root ganglion (DRG) neurons serve as the first-order sensory neurons relaying peripheral inputs to the spinal cord. Studies have shown that dopaminergic signalling contributes to the modulation of DRG neurons excitability and nociceptive transmission. In this study, we examined the effects of dopamine receptor subtypes on the excitability of small and large-sized DRG neurons using whole-cell patch-clamp recordings in acutely cultured rat DRG neurons. Activation of D1-like receptors by SKF38393 caused a depolarizing shift in the action potential threshold in small sized DRG neurons whereas an increase in spike width was observed in both small and large sized DRG neurons, suggesting reduced excitability likely mediated through modulation of sodium channel activity, whereas activation of D2-like receptors by ropinirole reduced the action potential amplitude and modulated the repolarization dynamics in small sized DRG neurons, indicating potential involvement of Gi-coupled mechanisms affecting sodium and potassium currents. Together, these findings demonstrate subtype-specific modulation of DRG neurons excitability by dopamine and highlight the peripheral dopaminergic system as a critical regulator of nociceptive signalling with potential implications for pain management.</p>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":" ","pages":"138579"},"PeriodicalIF":2.0,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147474523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Astrocytes preserve synaptic function and maintain excitatory–inhibitory balance by regulating neurotransmitter homeostasis, notably through the clearance of glutamate from the extracellular space. This process is essential for preventing excitotoxicity in the central nervous system. Mutations in glial fibrillary acidic protein (GFAP) are associated with astrocytic dysfunction, leading to neurological symptoms, e.g., seizures. Although such mutations are implicated in neurological disorders including Alexander disease, their direct impact on the astrocytic uptake of synaptically released glutamate has not been demonstrated. Here, we assessed glutamate uptake in hippocampal astrocytes of mice expressing mutant GFAP using whole-cell recordings of transporter-mediated currents in acute hippocampal slices. Glutamate release into the synaptic cleft varied according to the intensity of afferent fiber stimulation, but transporter current amplitudes did not differ significantly between mutant and control mice under baseline conditions. In contrast, when adenosine A1 receptors were blocked to relieve the tonic inhibition of glutamate release, transporter currents were significantly smaller in mutant mice than in controls at high stimulation intensities. These findings indicate that astrocytes expressing mutant GFAP exhibit impaired glutamate uptake capacity, which may be insufficient to prevent excitotoxicity or seizures under conditions of excessive glutamate release.
{"title":"Mutant glial fibrillary acidic protein reduces the capacity for glutamate uptake in hippocampal astrocytes","authors":"Yoshihiko Yamazaki , Hiroki Fujiwara , Jun-Ichi Goto , Kenji F. Tanaka","doi":"10.1016/j.neulet.2026.138511","DOIUrl":"10.1016/j.neulet.2026.138511","url":null,"abstract":"<div><div>Astrocytes preserve synaptic function and maintain excitatory–inhibitory balance by regulating neurotransmitter homeostasis, notably through the clearance of glutamate from the extracellular space. This process is essential for preventing excitotoxicity in the central nervous system. Mutations in glial fibrillary acidic protein (GFAP) are associated with astrocytic dysfunction, leading to neurological symptoms, e.g., seizures. Although such mutations are implicated in neurological disorders including Alexander disease, their direct impact on the astrocytic uptake of synaptically released glutamate has not been demonstrated. Here, we assessed glutamate uptake in hippocampal astrocytes of mice expressing mutant GFAP using whole-cell recordings of transporter-mediated currents in acute hippocampal slices. Glutamate release into the synaptic cleft varied according to the intensity of afferent fiber stimulation, but transporter current amplitudes did not differ significantly between mutant and control mice under baseline conditions. In contrast, when adenosine A<sub>1</sub> receptors were blocked to relieve the tonic inhibition of glutamate release, transporter currents were significantly smaller in mutant mice than in controls at high stimulation intensities. These findings indicate that astrocytes expressing mutant GFAP exhibit impaired glutamate uptake capacity, which may be insufficient to prevent excitotoxicity or seizures under conditions of excessive glutamate release.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"874 ","pages":"Article 138511"},"PeriodicalIF":2.0,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145981791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-15Epub Date: 2026-01-16DOI: 10.1016/j.neulet.2026.138510
Sara M. Klick , Cristina Rubino , Justine R. Magnuson , Lauren Penko , Anjana Rajendran , Ronan Denyer , Christina B. Jones , Jordan Brocato , Chris Lamb , Cristina Schaurich , Lara A. Boyd , Sarah N. Kraeutner
Stroke results in motor impairments of the upper limbs, linked to altered activation in sensorimotor regions. Motor imagery (MI; the mental rehearsal of movement) activates sensorimotor regions, providing the basis for its effectiveness as an intervention for motor recovery after stroke. Yet, the effect of repeated MI on brain activation after stroke is unexplored. In this study, thirty-three individuals with stroke (>3 months) performed MI of an upper-limb movement using their paretic arm and hand across two sessions on two different days. Brain activation was obtained via functional magnetic resonance imaging (fMRI). Group-level contrasts revealed: 1) focal brain activation in Session 2 relative to Session 1, and 2) functional localization to sensorimotor regions. Together, these findings demonstrate that MI induces changes in brain activation after only two sessions in individuals with stroke, specifically encompassing activation in sensorimotor areas. Familiarizing individuals to MI prior to its use may improve applications of MI for learning and recovery.
{"title":"Repeated exposure to motor imagery enhances focal brain activation during motor imagery practice after stroke","authors":"Sara M. Klick , Cristina Rubino , Justine R. Magnuson , Lauren Penko , Anjana Rajendran , Ronan Denyer , Christina B. Jones , Jordan Brocato , Chris Lamb , Cristina Schaurich , Lara A. Boyd , Sarah N. Kraeutner","doi":"10.1016/j.neulet.2026.138510","DOIUrl":"10.1016/j.neulet.2026.138510","url":null,"abstract":"<div><div>Stroke results in motor impairments of the upper limbs, linked to altered activation in sensorimotor regions. Motor imagery (MI; the mental rehearsal of movement) activates sensorimotor regions, providing the basis for its effectiveness as an intervention for motor recovery after stroke. Yet, the effect of repeated MI on brain activation after stroke is unexplored. In this study, thirty-three individuals with stroke (>3 months) performed MI of an upper-limb movement using their paretic arm and hand across two sessions on two different days. Brain activation was obtained via functional magnetic resonance imaging (fMRI). Group-level contrasts revealed: 1) focal brain activation in Session 2 relative to Session 1, and 2) functional localization to sensorimotor regions. Together, these findings demonstrate that MI induces changes in brain activation after only two sessions in individuals with stroke, specifically encompassing activation in sensorimotor areas. Familiarizing individuals to MI prior to its use may improve applications of MI for learning and recovery.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"874 ","pages":"Article 138510"},"PeriodicalIF":2.0,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145998444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-15Epub Date: 2026-01-08DOI: 10.1016/j.neulet.2026.138504
Zhouli Yue , Mengyuan Li , Jiahui Wang , Siqi Quan , Yiqi Wang , Zhanying Niu , Yucheng Li
Neuroinflammation is a key pathological feature of central nervous system disorders, yet its temporal and regional dynamics remain poorly defined. In this study, we systematically investigated neuroinflammatory responses and neuronal injury in the hippocampus and prefrontal cortex following a single intraperitoneal injection of lipopolysaccharide (LPS, 1 mg/kg) in mice. Fifty-four male C57BL/6N mice were randomly divided into six groups, and serum and brain tissues were collected at 0, 3, 6, 12, 24, and 48 h after LPS administration. Cytokine levels were detected by enzyme-linked immunosorbent assay (ELISA), neuronal injury was assessed by Nissl staining, and proteins expression was examined by Western blot. The results showed that peripheral cytokines, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6), exhibited a rapid and transient increase, peaking at 3 h and returning to baseline within 24 h, whereas central inflammatory responses displayed marked region- and time-dependent differences. In the hippocampus, IL-1β showed delayed but sustained elevation, peaking at 12 h and accompanied by progressive neuronal injury. In contrast, the prefrontal cortex exhibited an early cytokines surge at 3 h, with prolonged IL-1β elevation, and a biphasic pattern of neuronal damage characterized by early injury, partial recovery, and delayed exacerbation. These spatiotemporal dynamics were paralleled by differential activation of the TLR4/MyD88/NF-κB pathway. These findings reveal that LPS-induced neuroinflammation is a heterogeneous and dynamic process rather than a uniform response, providing new insight into region-specific vulnerability and the dissociation between peripheral and central inflammatory kinetics.
{"title":"Differential neuroinflammatory trajectories in the hippocampus and prefrontal cortex after acute LPS administration","authors":"Zhouli Yue , Mengyuan Li , Jiahui Wang , Siqi Quan , Yiqi Wang , Zhanying Niu , Yucheng Li","doi":"10.1016/j.neulet.2026.138504","DOIUrl":"10.1016/j.neulet.2026.138504","url":null,"abstract":"<div><div>Neuroinflammation is a key pathological feature of central nervous system disorders, yet its temporal and regional dynamics remain poorly defined. In this study, we systematically investigated neuroinflammatory responses and neuronal injury in the hippocampus and prefrontal cortex following a single intraperitoneal injection of lipopolysaccharide (LPS, 1 mg/kg) in mice. Fifty-four male C57BL/6N mice were randomly divided into six groups, and serum and brain tissues were collected at 0, 3, 6, 12, 24, and 48 h after LPS administration. Cytokine levels were detected by enzyme-linked immunosorbent assay (ELISA), neuronal injury was assessed by Nissl staining, and proteins expression was examined by Western blot. The results showed that peripheral cytokines, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6), exhibited a rapid and transient increase, peaking at 3 h and returning to baseline within 24 h, whereas central inflammatory responses displayed marked region- and time-dependent differences. In the hippocampus, IL-1β showed delayed but sustained elevation, peaking at 12 h and accompanied by progressive neuronal injury. In contrast, the prefrontal cortex exhibited an early cytokines surge at 3 h, with prolonged IL-1β elevation, and a biphasic pattern of neuronal damage characterized by early injury, partial recovery, and delayed exacerbation. These spatiotemporal dynamics were paralleled by differential activation of the TLR4/MyD88/NF-κB pathway. These findings reveal that LPS-induced neuroinflammation is a heterogeneous and dynamic process rather than a uniform response, providing new insight into region-specific vulnerability and the dissociation between peripheral and central inflammatory kinetics.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"874 ","pages":"Article 138504"},"PeriodicalIF":2.0,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145949146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-15Epub Date: 2026-01-14DOI: 10.1016/j.neulet.2026.138520
Maciej Klimiuk , Hanna Kletkiewicz , Joanna Wyszkowska , Karol Dokladny , Justyna Rogalska
Extremely low-frequency electromagnetic field (ELF-EMF) therapy is gaining attention for its potential benefits in treating neurodegenerative conditions. However, the underlying molecular mechanisms responsible for the possible protective effects of ELF-EMF remain unclear. Our previous research revealed that ELF-EMF exposure can establish a new “set-point” for stress responses, with outcomes dependent on field intensity. Stress hormones have been shown to modulate hippocampal function and plasticity. Therefore, our study aimed to assess how ELF-EMF exposure affects the expression of transcripts related to hippocampal plasticity, including genes related to neurogenesis (BDNF, TrkB, GAP43), synaptic activity (PSD95, SYN1), and cell survival (Bcl-2, Bcl-xL, Bak1). Adult rats were exposed to ELF-EMF (50 Hz) at 1 mT and 7 mT intensities for three 7-day periods, 1 h/day, with 3-week break between each cycle. A subset of animals was sacrificed after each exposure to collect hippocampi. The relative expression of neural/synaptic genes and anti-/pro-survival factors was measured by real-time quantitative polymerase chain reaction. Our findings indicate that ELF-EMF exposure modulates mRNA expression of neural/synaptic genes and anti-/pro-survival factors. The direction and dynamics of changes depend on ELF-EMF intensity and the number of exposures. “Low-intensity” ELF-EMF (1 mT) increased pro-neuroplastic factors expression, while “high-intensity” ELF-EMF (7 mT) decreased them. In summary, “low-intensity” ELF-EMF enhances adaptive processes like neuroplasticity by eliciting a mild stress response, while “high-intensity” exposure disrupts homeostasis and brain function by inducing severe stress. Our findings indicate that the overall effects of ELF-EMF depend on the intricate interplay between stress reactions and long-term brain plasticity.
{"title":"Dose-dependent impact of extremely low-frequency electromagnetic field (ELF-EMF) on the neuroplasticity in the hippocampus of adult rats","authors":"Maciej Klimiuk , Hanna Kletkiewicz , Joanna Wyszkowska , Karol Dokladny , Justyna Rogalska","doi":"10.1016/j.neulet.2026.138520","DOIUrl":"10.1016/j.neulet.2026.138520","url":null,"abstract":"<div><div>Extremely low-frequency electromagnetic field (ELF-EMF) therapy is gaining attention for its potential benefits in treating neurodegenerative conditions. However, the underlying molecular mechanisms responsible for the possible protective effects of ELF-EMF remain unclear. Our previous research revealed that ELF-EMF exposure can establish a new “set-point” for stress responses, with outcomes dependent on field intensity. Stress hormones have been shown to modulate hippocampal function and plasticity. Therefore, our study aimed to assess how ELF-EMF exposure affects the expression of transcripts related to hippocampal plasticity, including genes related to neurogenesis (BDNF, TrkB, GAP43), synaptic activity (PSD95, SYN1), and cell survival (Bcl-2, Bcl-xL, Bak1). Adult rats were exposed to ELF-EMF (50 Hz) at 1 mT and 7 mT intensities for three 7-day periods, 1 h/day, with 3-week break between each cycle. A subset of animals was sacrificed after each exposure to collect hippocampi. The relative expression of neural/synaptic genes and anti-/pro-survival factors was measured by real-time quantitative polymerase chain reaction. Our findings indicate that ELF-EMF exposure modulates mRNA expression of neural/synaptic genes and anti-/pro-survival factors. The direction and dynamics of changes depend on ELF-EMF intensity and the number of exposures. “Low-intensity” ELF-EMF (1 mT) increased pro-neuroplastic factors expression, while “high-intensity” ELF-EMF (7 mT) decreased them. In summary, “low-intensity” ELF-EMF enhances adaptive processes like neuroplasticity by eliciting a mild stress response, while “high-intensity” exposure disrupts homeostasis and brain function by inducing severe stress. Our findings indicate that the overall effects of ELF-EMF depend on the intricate interplay between stress reactions and long-term brain plasticity.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"874 ","pages":"Article 138520"},"PeriodicalIF":2.0,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145981695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Type I bipolar disorder (BD-I) affects approximately 1% of the global population, and alterations in the morphology of the hippocampus, a cerebral region critical for memory and emotional regulation, may play an important role in its pathophysiology. Childhood Adversity (CA), including abuse and neglect, has been linked to structural hippocampal changes and elevated psychiatric risk, yet the impact of CA on hippocampal subfields in BD remains poorly understood.
Methods
Eighty‑five euthymic patients with BD-I on stable lithium therapy (age 18–40), and 59 healthy controls were assessed (both groups trauma-exposed with score of Childhood Trauma Questionnaire (CTQ) > 25). Volumes of 12 hippocampal subfields were measured using FreeSurfer v6.0.0 and ENIGMA protocols. Partial correlations between CTQ subscale scores and subfield volumes were identified, controlling for age, sex, lithium use, and intracranial volume.
Results
In the BD-I group, higher physical neglect scores correlated with larger right hippocampal volumes: total hippocampus, CA1, hippocampal fissure, and presubiculum, whereas high emotional abuse scores were associated with increased left hippocampal fissure and subiculum volume. No significant associations were observed in controls, indicating specificity of trauma‑related alterations in BD-I.
Conclusion
Different CA subtypes yield distinct volumetric signatures in BD-I: physical neglect seems to drive expansion especially in right‑hemisphere subfields, while emotional abuse appears to enlarge the left subiculum. These findings highlight potential neuroplasticity biomarkers and may help inform early and targeted interventions.
{"title":"The role of childhood trauma in hippocampal subfield alterations in lithium-treated type I bipolar disorder and healthy controls: A subfield volumetry MRI study","authors":"Júnior Aparecido-de-Almeida , Marcio Gerhardt Soeiro-de-Souza","doi":"10.1016/j.neulet.2026.138503","DOIUrl":"10.1016/j.neulet.2026.138503","url":null,"abstract":"<div><h3>Background</h3><div>Type I bipolar disorder (BD-I) affects approximately 1% of the global population, and alterations in the morphology of the hippocampus, a cerebral region critical for memory and emotional regulation, may play an important role in its pathophysiology. Childhood Adversity (CA), including abuse and neglect, has been linked to structural hippocampal changes and elevated psychiatric risk, yet the impact of CA on hippocampal subfields in BD remains poorly understood.</div></div><div><h3>Methods</h3><div>Eighty‑five euthymic patients with BD-I on stable lithium therapy (age 18–40), and 59 healthy controls were assessed (both groups trauma-exposed with score of Childhood Trauma Questionnaire (CTQ) > 25). Volumes of 12 hippocampal subfields were measured using FreeSurfer v6.0.0 and ENIGMA protocols. Partial correlations between CTQ subscale scores and subfield volumes were identified, controlling for age, sex, lithium use, and intracranial volume.</div></div><div><h3>Results</h3><div>In the BD-I group, higher physical neglect scores correlated with larger right hippocampal volumes: total hippocampus, CA1, hippocampal fissure, and presubiculum, whereas high emotional abuse scores were associated with increased left hippocampal fissure and subiculum volume. No significant associations were observed in controls, indicating specificity of trauma‑related alterations in BD-I.</div></div><div><h3>Conclusion</h3><div>Different CA subtypes yield distinct volumetric signatures in BD-I: physical neglect seems to drive expansion especially in right‑hemisphere subfields, while emotional abuse appears to enlarge the left subiculum. These findings highlight potential neuroplasticity biomarkers and may help inform early and targeted interventions.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"874 ","pages":"Article 138503"},"PeriodicalIF":2.0,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145912385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-15Epub Date: 2026-01-06DOI: 10.1016/j.neulet.2026.138505
Jianchang Luo , Liyao Feng , Wenbin Xu, Jiawang Lang, Luodan Wang, Zhipeng Zhao, Boxu Lang
Migraine is a complex neuro-glio-vascular disorder, and electroacupuncture (EA) have been recommended as an alternative therapy for migraine. However, the mechanism of action of EA on GV20 (Baihui) and GV24 (Shenting) acupoints in treating migraine remains unclear. Thus, this study was performed to explore the potential mechanisms underlying the therapeutic influence of EA stimulation at GV20 and GV24 acupoints in the migraine treatment. After therapeutic effects of EA stimulation at GV20 and GV24 acupoints on migraine rat model established by dural electrical stimuli (DES) stimulation exploration, numerous approaches, such as qRT-PCR, immunofluorescence, and western blot, were applied to assess the expression of Piezo1 and pyroptosis-related proteins. Finally, Piezo1 activator (Yoda1) was used to confirm the involvement of Piezo1 channel in the treatment actions of EA stimulation at GV20 and GV24 acupoints on migraine. The results showed that EA stimulation at GV20 and GV24 acupoints forcefully alleviated the mechanical allodynia and central sensitization in rat model of migraine, also downregulated the expression of pro-inflammatory cytokines, containing TNF-α, IL-6, and IL-1β. In addition, EA stimulation at GV20 and GV24 acupoints also changed the expression of Piezo1 and pyroptosis-related proteins in rat model of migraine. Interestingly, treatment with the Yoda1 could reverse the therapeutic influences of EA stimulation at GV20 and GV24 acupoints in migraine rat model. Of note, the effect of EA stimulation at GV20 and GV24 acupoints on the expression of pyroptosis-related proteins could also be reverse by Yoda1 administration. This study emphasizes the EA efficacy at GV20 and GV24 acupoints on the migraine rat model established by DES stimulation, and proposes a mechanism involving inhibition of Piezo1 channel to block NLRP3-mediated pyroptosis in migraine.
{"title":"Electroacupuncture at GV20 and GV24 acupoints ameliorates migraine by blocking NLRP3-mediated pyroptosis via inhibiting the Piezo1 channel","authors":"Jianchang Luo , Liyao Feng , Wenbin Xu, Jiawang Lang, Luodan Wang, Zhipeng Zhao, Boxu Lang","doi":"10.1016/j.neulet.2026.138505","DOIUrl":"10.1016/j.neulet.2026.138505","url":null,"abstract":"<div><div>Migraine is a complex neuro-glio-vascular disorder, and electroacupuncture (EA) have been recommended as an alternative therapy for migraine. However, the mechanism of action of EA on GV20 (Baihui) and GV24 (Shenting) acupoints in treating migraine remains unclear. Thus, this study was performed to explore the potential mechanisms underlying the therapeutic influence of EA stimulation at GV20 and GV24 acupoints in the migraine treatment. After therapeutic effects of EA stimulation at GV20 and GV24 acupoints on migraine rat model established by dural electrical stimuli (DES) stimulation exploration, numerous approaches, such as qRT-PCR, immunofluorescence, and western blot, were applied to assess the expression of Piezo1 and pyroptosis-related proteins. Finally, Piezo1 activator (Yoda1) was used to confirm the involvement of Piezo1 channel in the treatment actions of EA stimulation at GV20 and GV24 acupoints on migraine. The results showed that EA stimulation at GV20 and GV24 acupoints forcefully alleviated the mechanical allodynia and central sensitization in rat model of migraine, also downregulated the expression of pro-inflammatory cytokines, containing TNF-α, IL-6, and IL-1β. In addition, EA stimulation at GV20 and GV24 acupoints also changed the expression of Piezo1 and pyroptosis-related proteins in rat model of migraine. Interestingly, treatment with the Yoda1 could reverse the therapeutic influences of EA stimulation at GV20 and GV24 acupoints in migraine rat model. Of note, the effect of EA stimulation at GV20 and GV24 acupoints on the expression of pyroptosis-related proteins could also be reverse by Yoda1 administration. This study emphasizes the EA efficacy at GV20 and GV24 acupoints on the migraine rat model established by DES stimulation, and proposes a mechanism involving inhibition of Piezo1 channel to block NLRP3-mediated pyroptosis in migraine.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"874 ","pages":"Article 138505"},"PeriodicalIF":2.0,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145934358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Antibody-based therapeutics are promising for treating central nervous system (CNS) diseases; however, brain delivery is severely restricted by the blood–brain barrier (BBB). Intranasal administration has gained attention as a noninvasive route proposed to reduce the impact of the BBB; however, the efficiency of delivering large biomolecules, such as antibodies, remains insufficiently characterized. This study aimed to investigate whether cell-penetrating peptides (CPPs) could increase detectable IgG levels in the cerebrospinal fluid (CSF) following intranasal administration in mice. Rabbit IgG was intranasally administered to ICR mice, either alone or in combination with CPPs (R9, Penetratin, or L17E). IgG levels in the CSF and serum were quantified by ELISA, and both time-course and dose-dependent effects were analyzed. IgG alone was not detected in the CSF, whereas serum IgG levels increased dose-dependently. Co-administration of Penetratin or L17E resulted in detectable CSF IgG levels, with L17E exceeding Penetratin. By contrast, no delivery was observed in the R9 group. Serum IgG levels also increased in the Penetratin and L17E groups. Time-course analysis with L17E showed that CSF IgG reached its highest measured level at 24 h and declined thereafter, whereas serum IgG reached higher levels at earlier time points and remained relatively stable. Dose–response analysis revealed linear increases in serum IgG, while CSF IgG levels depended on the concentration of L17E. These findings indicate that co-administration with amphipathic CPPs, particularly L17E, enables detectable IgG delivery to the CSF following intranasal administration in mice, although the underlying mechanisms and therapeutic relevance remain to be clarified.
{"title":"L17E cell-penetrating peptide enhances intranasal delivery of IgG to the cerebrospinal fluid in mice","authors":"Naoya Hashikawa, Taiki Terado, Takuya Noda, Riyo Kashimoto, Takumi Iima, Masamune Oro, Sora Tambara, Narumi Hashikawa-Hobara","doi":"10.1016/j.neulet.2026.138521","DOIUrl":"10.1016/j.neulet.2026.138521","url":null,"abstract":"<div><div>Antibody-based therapeutics are promising for treating central nervous system (CNS) diseases; however, brain delivery is severely restricted by the blood–brain barrier (BBB). Intranasal administration has gained attention as a noninvasive route proposed to reduce the impact of the BBB; however, the efficiency of delivering large biomolecules, such as antibodies, remains insufficiently characterized. This study aimed to investigate whether cell-penetrating peptides (CPPs) could increase detectable IgG levels in the cerebrospinal fluid (CSF) following intranasal administration in mice. Rabbit IgG was intranasally administered to ICR mice, either alone or in combination with CPPs (R9, Penetratin, or L17E). IgG levels in the CSF and serum were quantified by ELISA, and both time-course and dose-dependent effects were analyzed. IgG alone was not detected in the CSF, whereas serum IgG levels increased dose-dependently. Co-administration of Penetratin or L17E resulted in detectable CSF IgG levels, with L17E exceeding Penetratin. By contrast, no delivery was observed in the R9 group. Serum IgG levels also increased in the Penetratin and L17E groups. Time-course analysis with L17E showed that CSF IgG reached its highest measured level at 24 h and declined thereafter, whereas serum IgG reached higher levels at earlier time points and remained relatively stable. Dose–response analysis revealed linear increases in serum IgG, while CSF IgG levels depended on the concentration of L17E. These findings indicate that co-administration with amphipathic CPPs, particularly L17E, enables detectable IgG delivery to the CSF following intranasal administration in mice, although the underlying mechanisms and therapeutic relevance remain to be clarified.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"874 ","pages":"Article 138521"},"PeriodicalIF":2.0,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-12DOI: 10.1016/j.neulet.2026.138572
Yue Wu, Jinwei Pang, Jianhua Peng, Fang Cao, Michael P Vitek, Fengqiao Li, Yong Jiang, Xiaochuan Sun
{"title":"Retraction notice to \"An apoE-derived mimic peptide, COG1410, alleviates early brain injury via reducing apoptosis and neuroinflammation in a mouse model of subarachnoid hemorrhage\" [Neurosci. Lett. 627 (2016) 92-99].","authors":"Yue Wu, Jinwei Pang, Jianhua Peng, Fang Cao, Michael P Vitek, Fengqiao Li, Yong Jiang, Xiaochuan Sun","doi":"10.1016/j.neulet.2026.138572","DOIUrl":"10.1016/j.neulet.2026.138572","url":null,"abstract":"","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":" ","pages":"138572"},"PeriodicalIF":2.0,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147458986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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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