Pub Date : 2025-02-06DOI: 10.1016/j.neulet.2024.138091
Zirong Li , Yi Shu , Qian Liu , Deguo Liu , Sheng Xie , Mingjun Wei , Lidan Lan , Xinyi Yang
This study established an animal model of comorbid depression and insomnia by combining chronic unpredictable mild stress (CUMS) with sleep deprivation (SD). The pathogenesis of comorbid depression and insomnia may be associated with impaired AMPK/FOXO3a signaling, which mediates autophagy inhibition, leading to decreased pineal melatonin secretion. The findings revealed that CUMS + SD rats exhibited more pronounced depression-like behaviors, sleep disorders, increased central oxidative stress, and exacerbated neuroinflammation, accompanied by reduced levels of 5-hydroxytryptophan (5-HT) and melatonin in the pineal gland. Notably, further investigations revealed that impaired mitochondrial autophagy in the pineal gland is closely linked to the significant suppression of AMPK/FOXO3a signaling. The combined intervention of venlafaxine and melatonin effectively ameliorated the impaired mitochondrial autophagy in the pineal gland of CUMS + SD rats and stimulated melatonin secretion. Consequently, the study proposes that dysfunctional mitochondrial autophagy regulated by the AMPK/FOXO3a pathway can influence melatonin secretion, thereby playing a pivotal role in the pathogenesis of depression combined with insomnia.
{"title":"Sleep deprivation activated AMPK/FOXO3a signaling mediates pineal autophagy impairment to reduce melatonin secretion in CUMS + SD rats leading to depression combined with insomnia","authors":"Zirong Li , Yi Shu , Qian Liu , Deguo Liu , Sheng Xie , Mingjun Wei , Lidan Lan , Xinyi Yang","doi":"10.1016/j.neulet.2024.138091","DOIUrl":"10.1016/j.neulet.2024.138091","url":null,"abstract":"<div><div>This study established an animal model of comorbid depression and insomnia by combining chronic unpredictable mild stress (CUMS) with sleep deprivation (SD). The pathogenesis of comorbid depression and insomnia may be associated with impaired AMPK/FOXO3a signaling, which mediates autophagy inhibition, leading to decreased pineal melatonin secretion. The findings revealed that CUMS + SD rats exhibited more pronounced depression-like behaviors, sleep disorders, increased central oxidative stress, and exacerbated neuroinflammation, accompanied by reduced levels of 5-hydroxytryptophan (5-HT) and melatonin in the pineal gland. Notably, further investigations revealed that impaired mitochondrial autophagy in the pineal gland is closely linked to the significant suppression of AMPK/FOXO3a signaling. The combined intervention of venlafaxine and melatonin effectively ameliorated the impaired mitochondrial autophagy in the pineal gland of CUMS + SD rats and stimulated melatonin secretion. Consequently, the study proposes that dysfunctional mitochondrial autophagy regulated by the AMPK/FOXO3a pathway can influence melatonin secretion, thereby playing a pivotal role in the pathogenesis of depression combined with insomnia.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"848 ","pages":"Article 138091"},"PeriodicalIF":2.5,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-06DOI: 10.1016/j.neulet.2025.138118
Aniket Aman , Aaryaman Hoskote , Kshitij S. Jadhav , Bharat Aggarwal
Background
Clinical brain MRI scans, including contrast-enhanced (CE-MR) images, represent an underutilized resource for neuroscience research due to technical heterogeneity.
Purpose
To evaluate the reliability of morphometric measurements from CE-MR scans compared to non-contrast MR (NC-MR) scans in normal individuals.
Methods
T1-weighted CE-MR and NC-MR scans from 59 normal participants (aged 21–73 years) were compared using CAT12 and SynthSeg+ segmentation tools. Volumetric measurements and age prediction efficacy were analyzed.
Results
SynthSeg+ demonstrated high reliability (ICCs > 0.90) for most brain structures between CE-MR and NC-MR scans, with discrepancies in CSF and ventricular volumes. CAT12 showed inconsistent performance. Age prediction models using SynthSeg + yielded comparable results for both scan types.
Conclusion
Deep learning-based approaches like SynthSeg+ can reliably process CE-MR scans for morphometric analysis, potentially broadening the application of clinically acquired CE-MR images in neuroimaging research.
{"title":"Comparative analysis of brain volumetric measurements between contrast-enhanced and non-contrast MRI images","authors":"Aniket Aman , Aaryaman Hoskote , Kshitij S. Jadhav , Bharat Aggarwal","doi":"10.1016/j.neulet.2025.138118","DOIUrl":"10.1016/j.neulet.2025.138118","url":null,"abstract":"<div><h3>Background</h3><div>Clinical brain MRI scans, including contrast-enhanced (CE-MR) images, represent an underutilized resource for neuroscience research due to technical heterogeneity.</div></div><div><h3>Purpose</h3><div>To evaluate the reliability of morphometric measurements from CE-MR scans compared to non-contrast MR (NC-MR) scans in normal individuals.</div></div><div><h3>Methods</h3><div>T1-weighted CE-MR and NC-MR scans from 59 normal participants (aged 21–73 years) were compared using CAT12 and SynthSeg+ segmentation tools. Volumetric measurements and age prediction efficacy were analyzed.</div></div><div><h3>Results</h3><div>SynthSeg+ demonstrated high reliability (ICCs > 0.90) for most brain structures between CE-MR and NC-MR scans, with discrepancies in CSF and ventricular volumes. CAT12 showed inconsistent performance. Age prediction models using SynthSeg + yielded comparable results for both scan types.</div></div><div><h3>Conclusion</h3><div>Deep learning-based approaches like SynthSeg+ can reliably process CE-MR scans for morphometric analysis, potentially broadening the application of clinically acquired CE-MR images in neuroimaging research.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"848 ","pages":"Article 138118"},"PeriodicalIF":2.5,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142952264","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 : 2025-02-06DOI: 10.1016/j.neulet.2024.138108
Carly Norris , Susan F. Murphy , Pamela J. VandeVord
Regulation of glutamate through glutamate-glutamine cycling is critical for mediating nervous system plasticity. Blast-induced traumatic brain injury (bTBI) has been linked to glutamate-dependent excitotoxicity, which may be potentiating chronic disorders such as post-traumatic epilepsy. The purpose of this study was to measure changes in the expression of astrocytic and neuronal proteins responsible for glutamatergic regulation at 4-, 12-, and 24 h in the cortex and hippocampus following single blast exposure in a rat model for bTBI. Animals were exposed to a blast with magnitudes ranging from 16 to 20 psi using an Advanced Blast Simulator, and western blotting was performed to compare changes in protein expression between blast and sham groups. Glial fibrillary acidic protein (GFAP) was increased at 24 h, consistent with astrocyte reactivity, yet no other proteins showed significant changes in expression at acute time points following blast (GS, GLT-1, GluN1, GluN2A, GluN2B). Therefore, these glutamate regulators likely do not play a major role in contributing to acute excitotoxicity or glial reactivity when analyzed by whole brain region. Investigation of substructural and subregional effects in future studies, particularly within the hippocampus (e.g., dentate gyrus, CA1, CA2, CA3), may reveal localized changes in expression and/or NMDAR subunit composition capable of potentiating bTBI molecular cascades. Nevertheless, alternative regulators are likely to demonstrate greater sensitivity as acute therapeutic targets contributing to bTBI pathophysiology following single blast exposure.
{"title":"Acute astrocytic and neuronal regulation of glutamatergic protein expression following blast","authors":"Carly Norris , Susan F. Murphy , Pamela J. VandeVord","doi":"10.1016/j.neulet.2024.138108","DOIUrl":"10.1016/j.neulet.2024.138108","url":null,"abstract":"<div><div>Regulation of glutamate through glutamate-glutamine cycling is critical for mediating nervous system plasticity. Blast-induced traumatic brain injury (bTBI) has been linked to glutamate-dependent excitotoxicity, which may be potentiating chronic disorders such as post-traumatic epilepsy. The purpose of this study was to measure changes in the expression of astrocytic and neuronal proteins responsible for glutamatergic regulation at 4-, 12-, and 24 h in the cortex and hippocampus following single blast exposure in a rat model for bTBI. Animals were exposed to a blast with magnitudes ranging from 16 to 20 psi using an Advanced Blast Simulator, and western blotting was performed to compare changes in protein expression between blast and sham groups. Glial fibrillary acidic protein (GFAP) was increased at 24 h, consistent with astrocyte reactivity, yet no other proteins showed significant changes in expression at acute time points following blast (GS, GLT-1, GluN1, GluN2A, GluN2B). Therefore, these glutamate regulators likely do not play a major role in contributing to acute excitotoxicity or glial reactivity when analyzed by whole brain region. Investigation of substructural and subregional effects in future studies, particularly within the hippocampus (e.g., dentate gyrus, CA1, CA2, CA3), may reveal localized changes in expression and/or NMDAR subunit composition capable of potentiating bTBI molecular cascades. Nevertheless, alternative regulators are likely to demonstrate greater sensitivity as acute therapeutic targets contributing to bTBI pathophysiology following single blast exposure.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"848 ","pages":"Article 138108"},"PeriodicalIF":2.5,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903269","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 : 2025-02-06DOI: 10.1016/j.neulet.2025.138150
Changjun Yang, John Aaron Howell, Lei Liu, Rachel E. Gunraj, Eduardo Candelario-Jalil
Adropin is a bioactive peptide found in the brain and various peripheral tissues. Evidence suggests that aging significantly decreases brain adropin levels, and interventions that elevate adropin may help alleviate age-related neurological disorders such as ischemic stroke and cognitive decline. However, the impact of aging on peripheral tissue adropin levels and its relationship with the neural recognition molecule NB-3/contactin-6 in the brain remains unclear. In this study, we quantified adropin using immunoblotting in brain and peripheral tissues (liver, lung, kidney, spleen, ileum, colon) from young (8–10 weeks) and aged (18–20 months) male mice. Results indicated a significant decrease in brain adropin levels in aged mice, while peripheral tissues showed no significant changes compared to young controls. Additionally, levels of NB-3/contactin-6, a potential adropin receptor and Notch1 ligand, were lower in aged brains. Co-immunoprecipitation demonstrated that adropin physically associates with brain NB-3. Notably, the age-related reduction in brain adropin correlates with increased oxidative stress markers (gp91phox and 4-hydroxynonenal). We provide the first evidence that aging is linked to a concurrent loss of adropin and NB-3 in the brain but not in peripheral tissues. Interventions to maintain brain adropin levels could help mitigate the brain’s aging process and alleviate age-related neurological dysfunction.
{"title":"Changes in adropin levels in brain and peripheral tissues with aging","authors":"Changjun Yang, John Aaron Howell, Lei Liu, Rachel E. Gunraj, Eduardo Candelario-Jalil","doi":"10.1016/j.neulet.2025.138150","DOIUrl":"10.1016/j.neulet.2025.138150","url":null,"abstract":"<div><div>Adropin is a bioactive peptide found in the brain and various peripheral tissues. Evidence suggests that aging significantly decreases brain adropin levels, and interventions that elevate adropin may help alleviate age-related neurological disorders such as ischemic stroke and cognitive decline. However, the impact of aging on peripheral tissue adropin levels and its relationship with the neural recognition molecule NB-3/contactin-6 in the brain remains unclear. In this study, we quantified adropin using immunoblotting in brain and peripheral tissues (liver, lung, kidney, spleen, ileum, colon) from young (8–10 weeks) and aged (18–20 months) male mice. Results indicated a significant decrease in brain adropin levels in aged mice, while peripheral tissues showed no significant changes compared to young controls. Additionally, levels of NB-3/contactin-6, a potential adropin receptor and Notch1 ligand, were lower in aged brains. Co-immunoprecipitation demonstrated that adropin physically associates with brain NB-3. Notably, the age-related reduction in brain adropin correlates with increased oxidative stress markers (gp91<sup>phox</sup> and 4-hydroxynonenal). We provide the first evidence that aging is linked to a concurrent loss of adropin and NB-3 in the brain but not in peripheral tissues. Interventions to maintain brain adropin levels could help mitigate the brain’s aging process and alleviate age-related neurological dysfunction.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"850 ","pages":"Article 138150"},"PeriodicalIF":2.5,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374330","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 : 2025-02-05DOI: 10.1016/j.neulet.2025.138149
Somayyeh Torabi , Zahra Zeraatpisheh , Seyed Hadi Anjamrooz , Amir Ghanbari , Syed Shadab Raza , Hadi Aligholi , Hassan Azari
Modulating the immune response following spinal cord injury (SCI) is vital for establishing a conducive microenvironment that supports the survival and engraftment of transplanted neural stem/progenitor cells (NSPCs). Building on our prior findings of ibrutinib’s immunotherapeutic potential in acute SCI, this study investigates the impact of ibrutinib administration on NSPC survival, fate and their potential synergistic effects on tissue repair and motor function in a contusive mouse model of SCI.
Green fluorescence expressing NSPCs were transplanted into the lesion site with or without concurrent ibrutinib administration. Over four weeks, comprehensive assessments included behavioral evaluations, lesion volume measurements, and analyses of the survival, fate, and migration patterns of the transplanted cells. The results revealed that ibrutinib and NSPCs individually reduced lesion volume and improved motor functions. However, their combination significantly accelerated and enhanced motor recovery. Furthermore, ibrutinib improved cell viability, increasing markers for oligodendrocyte and neuroblast while concurrently diminishing the expression of astrocyte marker glial fibrillary acidic protein (GFAP).
In conclusion, the combined utilization of ibrutinib and NSPC transplantation presents a promising strategy for enhancing tissue repair, promoting functional recovery, and positively modulating cell behaviors in the context of SCI.
{"title":"Synergistic effects of neural stem cells and ibrutinib on neural tissue repair and functional recovery in a contusion mouse model of spinal cord injury","authors":"Somayyeh Torabi , Zahra Zeraatpisheh , Seyed Hadi Anjamrooz , Amir Ghanbari , Syed Shadab Raza , Hadi Aligholi , Hassan Azari","doi":"10.1016/j.neulet.2025.138149","DOIUrl":"10.1016/j.neulet.2025.138149","url":null,"abstract":"<div><div>Modulating the immune response following spinal cord injury (SCI) is vital for establishing a conducive microenvironment that supports the survival and engraftment of transplanted neural stem/progenitor cells (NSPCs). Building on our prior findings of ibrutinib’s immunotherapeutic potential in acute SCI, this study investigates the impact of ibrutinib administration on NSPC survival, fate and their potential synergistic effects on tissue repair and motor function in a contusive mouse model of SCI.</div><div>Green fluorescence expressing NSPCs were transplanted into the lesion site with or without concurrent ibrutinib administration. Over four weeks, comprehensive assessments included behavioral evaluations, lesion volume measurements, and analyses of the survival, fate, and migration patterns of the transplanted cells. The results revealed that ibrutinib and NSPCs individually reduced lesion volume and improved motor functions. However, their combination significantly accelerated and enhanced motor recovery. Furthermore, ibrutinib improved cell viability, increasing markers for oligodendrocyte and neuroblast while concurrently diminishing the expression of astrocyte marker glial fibrillary acidic protein (GFAP).</div><div>In conclusion, the combined utilization of ibrutinib and NSPC transplantation presents a promising strategy for enhancing tissue repair, promoting functional recovery, and positively modulating cell behaviors in the context of SCI.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"850 ","pages":"Article 138149"},"PeriodicalIF":2.5,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143372658","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 : 2025-02-04DOI: 10.1016/j.neulet.2025.138148
Claudio M. Privitera , Sean Noah , Thom Carney , Stanley A. Klein , Agatha Lenartowicz , Stephen P. Hinshaw , James T. McCracken , Joel T. Nigg , Sarah L. Karalunas , Rory C. Reid , Mercedes Oliva , Samantha S. Betts , Gregory V. Simpson
We investigated the phenomenon of pupillary unrest in individuals with Attention Deficit Hyperactivity Disorder (ADHD) compared to neurotypical controls. We measured the power of low-frequency pupil oscillations under two experimental conditions: a passive condition with minimal distraction and a resting condition with no distraction. The study included 76 adult participants (42 controls and 34 with ADHD) aged 18–40. The results show that individuals with ADHD exhibit reduced power in pupillary oscillations, suggesting a suppression of general catecholaminergic activity. The nature of the experiment indicates that this suppression is endemic in the background and independent of the visual task or the ongoing cognitive effort. This finding is consistent with our previous observations of reduced pupil dilations in ADHD during active tasks [1] and provide basic insights for future research aimed at developing and refining a psychophysical paradigm that could serve as a biomarker to enhance ADHD evaluation and classification.
{"title":"Pupillary unrest is attenuated in attention deficit hyperactivity disorder (ADHD)","authors":"Claudio M. Privitera , Sean Noah , Thom Carney , Stanley A. Klein , Agatha Lenartowicz , Stephen P. Hinshaw , James T. McCracken , Joel T. Nigg , Sarah L. Karalunas , Rory C. Reid , Mercedes Oliva , Samantha S. Betts , Gregory V. Simpson","doi":"10.1016/j.neulet.2025.138148","DOIUrl":"10.1016/j.neulet.2025.138148","url":null,"abstract":"<div><div>We investigated the phenomenon of pupillary unrest in individuals with Attention Deficit Hyperactivity Disorder (ADHD) compared to neurotypical controls. We measured the power of low-frequency pupil oscillations under two experimental conditions: a passive condition with minimal distraction and a resting condition with no distraction. The study included 76 adult participants (42 controls and 34 with ADHD) aged 18–40. The results show that individuals with ADHD exhibit reduced power in pupillary oscillations, suggesting a suppression of general catecholaminergic activity. The nature of the experiment indicates that this suppression is endemic in the background and independent of the visual task or the ongoing cognitive effort. This finding is consistent with our previous observations of reduced pupil dilations in ADHD during active tasks <span><span>[1]</span></span> and provide basic insights for future research aimed at developing and refining a psychophysical paradigm that could serve as a biomarker to enhance ADHD evaluation and classification.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"851 ","pages":"Article 138148"},"PeriodicalIF":2.5,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.neulet.2025.138135
Jens D. Mikkelsen , Phoebe Linde-Atkins , Burcu A. Pazarlar
Neuronal and synapse losses are seen under the progression of Alzheimer’s disease (AD). Accordingly, the binding to the synaptic vesicle glycoprotein 2A (SV2A) using the selective radioligand [3H]UCB-J was found to be reduced in frontal cortex from patients with AD. We report here that the reduction in SV2A binding is highly significant only in patients not carrying the ApoE ɛ4 allele. By contrast, those individuals with one or two ApoE ɛ4 alleles had SV2A binding levels not different from controls. Because ApoE4 is an important genetic risk and strongly linked to late-onset AD, this study raises an interesting new and unexpected association to SV2A, synapse loss, and function.
{"title":"Higher level of [3H]UCB-J binding in ApoE Ɛ4 allele carriers with Alzheimer disease","authors":"Jens D. Mikkelsen , Phoebe Linde-Atkins , Burcu A. Pazarlar","doi":"10.1016/j.neulet.2025.138135","DOIUrl":"10.1016/j.neulet.2025.138135","url":null,"abstract":"<div><div>Neuronal and synapse losses are seen under the progression of Alzheimer’s disease (AD). Accordingly, the binding to the synaptic vesicle glycoprotein 2A (SV2A) using the selective radioligand [<sup>3</sup>H]UCB-J was found to be reduced in frontal cortex from patients with AD. We report here that the reduction in SV2A binding is highly significant only in patients not carrying the ApoE ɛ4 allele. By contrast, those individuals with one or two ApoE ɛ4 alleles had SV2A binding levels not different from controls. Because ApoE4 is an important genetic risk and strongly linked to late-onset AD, this study raises an interesting new and unexpected association to SV2A, synapse loss, and function.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"849 ","pages":"Article 138135"},"PeriodicalIF":2.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-31DOI: 10.1016/j.neulet.2024.138096
Jahangir Sajjad , Jennifer Morael , Thieza G. Melo , Tara Foley , Amy Murphy , James Keane , Jelena Popov , Catherine Stanton , Timothy G. Dinan , Gerard Clarke , John F. Cryan , James M. Collins , Siobhain M. O’Mahony
Pain and psychological stress are intricately linked, with sex differences evident in disorders associated with both systems. Glutamatergic signalling in the central nervous system is influenced by gonadal hormones via the hypothalamic–pituitary–adrenal axis and is central in pain research. Emerging evidence supports an important role for the gut microbiota in influencing pain signalling. Here, the functional activity of excitatory amino acid transporters (EAATs) in the anterior cingulate cortex (ACC) and lumbosacral spinal cord of male and female Wistar-Kyoto rats, an animal model of comorbid visceral hypersensitivity and enhanced stress responsivity, was investigated across the oestrous cycle. Correlations between the gut microbiota and changes in the functional activity of the central glutamatergic system were also investigated.
EAAT function in the lumbosacral spinal cord was similar between males and females across the oestrous cycle. EAAT function was higher in the ACC of dioestrus females compared to proestrus and oestrus females. In males, aspartate uptake in the ACC positively correlated with Bacteroides, while aspartate uptake in the spinal cord positively correlated with the relative abundance of Lachnospiraceae NK4A136. Positive associations with aspartate uptake in the spinal cord were also observed for Alistipes and Bifidobacterium during oestrus, and Eubacterium coprostanoligenes during proestrus. Clostridium sensu stricto1 was negatively associated with aspartate uptake in the ACC in males and dioestrus females.
These data indicate that glutamate metabolism in the ACC is oestrous stage-dependent and that short-chain fatty acid-producing bacteria are positively correlated with aspartate uptake in males and during specific oestrous stages in females.
{"title":"Differential cortical aspartate uptake across the oestrous cycle is associated with changes in gut microbiota in Wistar-Kyoto rats","authors":"Jahangir Sajjad , Jennifer Morael , Thieza G. Melo , Tara Foley , Amy Murphy , James Keane , Jelena Popov , Catherine Stanton , Timothy G. Dinan , Gerard Clarke , John F. Cryan , James M. Collins , Siobhain M. O’Mahony","doi":"10.1016/j.neulet.2024.138096","DOIUrl":"10.1016/j.neulet.2024.138096","url":null,"abstract":"<div><div>Pain and psychological stress are intricately linked, with sex differences evident in disorders associated with both systems. Glutamatergic signalling in the central nervous system is influenced by gonadal hormones via the hypothalamic–pituitary–adrenal axis and is central in pain research. Emerging evidence supports an important role for the gut microbiota in influencing pain signalling. Here, the functional activity of excitatory amino acid transporters (EAATs) in the anterior cingulate cortex (ACC) and lumbosacral spinal cord of male and female Wistar-Kyoto rats, an animal model of comorbid visceral hypersensitivity and enhanced stress responsivity, was investigated across the oestrous cycle. Correlations between the gut microbiota and changes in the functional activity of the central glutamatergic system were also investigated.</div><div>EAAT function in the lumbosacral spinal cord was similar between males and females across the oestrous cycle. EAAT function was higher in the ACC of dioestrus females compared to proestrus and oestrus females. In males, aspartate uptake in the ACC positively correlated with <em>Bacteroides</em>, while aspartate uptake in the spinal cord positively correlated with the relative abundance of <em>Lachnospiraceae NK4A136</em>. Positive associations with aspartate uptake in the spinal cord were also observed for <em>Alistipes</em> and <em>Bifidobacterium</em> during oestrus, and <em>Eubacterium coprostanoligenes</em> during proestrus. <em>Clostridium sensu stricto1</em> was negatively associated with aspartate uptake in the ACC in males and dioestrus females.</div><div>These data indicate that glutamate metabolism in the ACC is oestrous stage-dependent and that short-chain fatty acid-producing bacteria are positively correlated with aspartate uptake in males and during specific oestrous stages in females.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"847 ","pages":"Article 138096"},"PeriodicalIF":2.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882551","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 : 2025-01-31DOI: 10.1016/j.neulet.2024.138094
Ronyson Kharkongor, JenishaChris Stephen, UlfathTasneem Khan, Rameshkumar Radhakrishnan
An enriched environment (EE) constitutes a proficient strategy that instigates social, cognitive, and motor faculties, fostering healing and heightening learning and memory function after ischemia, while fucoidan derived from brown seaweed encompasses a diverse array of bioactivities and is known to possess neuroprotective properties. This study aims to investigate the effectiveness of combining fucoidan and EE in a rat model of vascular dementia to overcome cognitive challenges. The rats were randomly assigned as Sham, Lesion − 4-vessel occlusion (4VO) i.e., transient global cerebral ischemia (tGCI), 4VO + F50mg/kg, 4VO + EE, and 4VO + F50mg/kg + EE. At the end of the study periods, the rats were exposed to the Novel object task, T-maze, and the Morris water maze. The profile of hippocampal pyramidal neurons and their dendrites was assessed through the CFV, and Golgi cox stained brain sections. Neuroinflammatory markers (IL-1β, IL-6, NF-κB, TNF-α) and synaptogenic markers (BDNF, SYP, PSD-95) were evaluated through western blot analysis. The levels of oxidative stress marker (LPO) and antioxidants (SOD, CAT, GSH, GST, GPX) in the hippocampus were quantified through biochemical assay. The findings revealed that the cognitive deficits were significantly reduced in both the 4VO + F50mg/kg and 4VO + F50mg/kg + EE treatment groups and inflammatory markers were reduced with increased antioxidant levels and synaptogenic markers when compared with the lesion group. However, through this study, the combination therapy involving fucoidan and exposure to an EE was proven effective in preserving neural integrity and restoring cognitive function against the damage caused by oxidative stress and inflammation following tGCI.
{"title":"Exposure to an enriched environment and fucoidan supplementation ameliorate learning and memory function in rats subjected to global cerebral ischemia","authors":"Ronyson Kharkongor, JenishaChris Stephen, UlfathTasneem Khan, Rameshkumar Radhakrishnan","doi":"10.1016/j.neulet.2024.138094","DOIUrl":"10.1016/j.neulet.2024.138094","url":null,"abstract":"<div><div>An enriched environment (EE) constitutes a proficient strategy that instigates social, cognitive, and motor faculties, fostering healing and heightening learning and memory function after ischemia, while fucoidan derived from brown seaweed encompasses a diverse array of bioactivities and is known to possess neuroprotective properties. This study aims to investigate the effectiveness of combining fucoidan and EE in a rat model of vascular dementia to overcome cognitive challenges. The rats were randomly assigned as Sham, Lesion − 4-vessel occlusion (4VO) i.e., transient global cerebral ischemia (tGCI), 4VO + F50mg/kg, 4VO + EE, and 4VO + F50mg/kg + EE. At the end of the study periods, the rats were exposed to the Novel object task, T-maze, and the Morris water maze. The profile of hippocampal pyramidal neurons and their dendrites was assessed through the CFV, and Golgi cox stained brain sections. Neuroinflammatory markers (IL-1β, IL-6, NF-κB, TNF-α) and synaptogenic markers (BDNF, SYP, PSD-95) were evaluated through western blot analysis. The levels of oxidative stress marker (LPO) and antioxidants (SOD, CAT, GSH, GST, GPX) in the hippocampus were quantified through biochemical assay. The findings revealed that the cognitive deficits were significantly reduced in both the 4VO + F50mg/kg and 4VO + F50mg/kg + EE treatment groups and inflammatory markers were reduced with increased antioxidant levels and synaptogenic markers when compared with the lesion group. However, through this study, the combination therapy involving fucoidan and exposure to an EE was proven effective in preserving neural integrity and restoring cognitive function against the damage caused by oxidative stress and inflammation following tGCI.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"847 ","pages":"Article 138094"},"PeriodicalIF":2.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142907345","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 : 2025-01-31DOI: 10.1016/j.neulet.2024.138089
Jinming Liu , Yong Wang , Hong Sun , Daoyun Lei , Jufeng Liu , Yuanhui Fei , Chunhui Wang , Chao Han
Postoperative cognitive dysfunction (POCD) is a common cognitive challenge faced by older adults. One of the key contributors to the development of POCD is neuroinflammation induced by microglia. Resveratrol has emerged as a promising candidate for the prevention of cognitive decline. Previous studies have demonstrated its potential in alleviating cognitive deterioration, yielding encouraging results. Nonetheless, the mechanism of resveratrol improving cognitive function remains unclear. Therefore, we assessed the effect of resveratrol in both aged POCD model mice and BV2 cells on CX3CL1/CX3CR1 axis, a critical signaling pathway mediating microglial activity. Both in vitro and in vivo experiments have revealed that pre-administration of resveratrol not only mitigates cognitive deficits but also significantly reduces the levels of inflammatory cytokines. Additionally, it enhanced the expression of SIRT1 and CX3CR1 within the hippocampal region. We also evaluated the impact of resveratrol on CX3CR1 siRNA transfected BV2 cells. Delete of CX3CR1 reversed the preventive role of resveratrol. Our findings implied that resveratrol might inhibit microglial activation and improve cognition by mediating CX3CL1/CX3CR1 signaling.
{"title":"Resveratrol ameliorates postoperative cognitive dysfunction in aged mice by regulating microglial polarization through CX3CL1/CX3CR1 signaling axis","authors":"Jinming Liu , Yong Wang , Hong Sun , Daoyun Lei , Jufeng Liu , Yuanhui Fei , Chunhui Wang , Chao Han","doi":"10.1016/j.neulet.2024.138089","DOIUrl":"10.1016/j.neulet.2024.138089","url":null,"abstract":"<div><div>Postoperative cognitive dysfunction (POCD) is a common cognitive challenge faced by older adults. One of the key contributors to the development of POCD is neuroinflammation induced by microglia. Resveratrol has emerged as a promising candidate for the prevention of cognitive decline. Previous studies have demonstrated its potential in alleviating cognitive deterioration, yielding encouraging results. Nonetheless, the mechanism of resveratrol improving cognitive function remains unclear. Therefore, we assessed the effect of resveratrol in both aged POCD model mice and BV2 cells on CX3CL1/CX3CR1 axis, a critical signaling pathway mediating microglial activity. Both in vitro and in vivo experiments have revealed that pre-administration of resveratrol not only mitigates cognitive deficits but also significantly reduces the levels of inflammatory cytokines. Additionally, it enhanced the expression of SIRT1 and CX3CR1 within the hippocampal region. We also evaluated the impact of resveratrol on CX3CR1 siRNA transfected BV2 cells. Delete of CX3CR1 reversed the preventive role of resveratrol. Our findings implied that resveratrol might inhibit microglial activation and improve cognition by mediating CX3CL1/CX3CR1 signaling.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"847 ","pages":"Article 138089"},"PeriodicalIF":2.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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