Pub Date : 2025-02-03DOI: 10.1016/j.neuroscience.2025.02.003
Yan Yang , Wei Sun , Fan Yang , Ting Liang , Chun-Li Li , Yan Wang , Xiao-Liang Wang , Rui-Rui Wang , Shuang-Chan Wu , Jun Chen
Prediabetic neuropathic pain has been classified as peripheral neuropathic pain associated with polyneuropathy caused by impaired glucose tolerance or impaired fasting glucose, which is a preclinical stage and might develop type 2 diabetes mellitus. Our previous research highlighted that prediabetes is accompanied by dramatic bilateral mechanical hyperalgesia following high energy diet (HED) which results in myelin and axonal degenerations along somatosensory system. However, the pathogenic mechanisms underlying prediabetic neuropathic pain remain unclear. The nuclear sirtuin 6 (SIRT6) is a crucial deacetylase in the regulation of multiple cellular biological processes, such as DNA repair, genome stability, inflammation and metabolic homeostasis. In current study, we show that the expressions of SIRT6 were significantly decreased, while its downstream NF-κB and proinflammatory mediator IL-6 and IL-1β were significantly increased in both dorsal root ganglia (DRG) and spinal dorsal horn of rats with prediabetic neuropathic pain induced by HED. Moreover, siRNA-SIRT6 treatment induced a significant reduction in bilateral paw withdrawal mechanical thresholds, indicating that SIRT6 down-regulation contributed to prediabetic neuropathic pain induced by HED. Furthermore, it was also found that SIRT6 reduction induced the activation of HMGB1 via disinhibition of NF-κB in both DRG and spinal dorsal horn of prediabetic rats. In conclusion, prediabetic neuropathic pain is caused by SIRT6 reduction through upregulating HMGB1-RAGE signaling at both peripheral and spinal levels.
{"title":"High energy diet-induced prediabetic neuropathic pain is mediated by reduction of SIRT6 negative control of both spinal and peripheral neuroinflammation","authors":"Yan Yang , Wei Sun , Fan Yang , Ting Liang , Chun-Li Li , Yan Wang , Xiao-Liang Wang , Rui-Rui Wang , Shuang-Chan Wu , Jun Chen","doi":"10.1016/j.neuroscience.2025.02.003","DOIUrl":"10.1016/j.neuroscience.2025.02.003","url":null,"abstract":"<div><div>Prediabetic neuropathic pain has been classified as peripheral neuropathic pain associated with polyneuropathy caused by impaired glucose tolerance or impaired fasting glucose, which is a preclinical stage and might develop type 2 diabetes mellitus. Our previous research highlighted that prediabetes is accompanied by dramatic bilateral mechanical hyperalgesia following high energy diet (HED) which results in myelin and axonal degenerations along somatosensory system. However, the pathogenic mechanisms underlying prediabetic neuropathic pain remain unclear. The nuclear sirtuin 6 (SIRT6) is a crucial deacetylase in the regulation of multiple cellular biological processes, such as DNA repair, genome stability, inflammation and metabolic homeostasis. In current study, we show that the expressions of SIRT6 were significantly decreased, while its downstream NF-κB and proinflammatory mediator IL-6 and IL-1β were significantly increased in both dorsal root ganglia (DRG) and spinal dorsal horn of rats with prediabetic neuropathic pain induced by HED. Moreover, siRNA-SIRT6 treatment induced a significant reduction in bilateral paw withdrawal mechanical thresholds, indicating that SIRT6 down-regulation contributed to prediabetic neuropathic pain induced by HED. Furthermore, it was also found that SIRT6 reduction induced the activation of HMGB1 via disinhibition of NF-κB in both DRG and spinal dorsal horn of prediabetic rats. In conclusion, prediabetic neuropathic pain is caused by SIRT6 reduction through upregulating HMGB1-RAGE signaling at both peripheral and spinal levels.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"569 ","pages":"Pages 58-66"},"PeriodicalIF":2.9,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-02DOI: 10.1016/j.neuroscience.2025.01.067
Xiao Li , Qian Zheng , Honghong Yu , Tingting Du , Tian Hu , Lanyue Gao , Lihong Jia , Qi Sun
Sleep plays an important role in the process of memory. This study investigated the role of the circadian clock gene, BMAL1 of the master circadian clock in mediating the impairment of hippocampus-dependent recognition memory caused by sleep deprivation. After 4 weeks of sleep deprivation, the novel object recognitiontask was used to evaluate the recognition memory of mice, the expression levels of circadian clock genes, and Nrf2 and PKA/CREB/BDNF signal pathways were detected by Western blot, Realtime-qPCR, and immunofluorescence. The mice in the SD group exhibited a significant decrease in the duration of exploration of novel objects. The protein expression levels of PER1, PER2, CLOCK, and BMAL1, and PKA/CREB/BDNF pathway in the hippocampus of the SD group were significantly reduced, and the Nrf2-mediated anti-oxidative capacity was also compromised in the SD group. Moreover, these aberrations could be mitigated through compensation with BMAL1 in the SCN of the hypothalamus. Sleep deprivation resulted in a reduction in the expression of the core clock gene BMAL1 in the hippocampus, leading to an imbalance in the antioxidant system and damaging down-regulating the PKA/CREB/BDNF signal pathway that related to the proteins associated with recognition memory in the hippocampal synapse plasticity and oxidative stress, which could be reversed by overexpression compensation of BMAL1 in the SCN that might rely on the multi-synaptic neural projections to the hippocampus.
{"title":"BMAL1 rescued the hippocampus-dependent recognition memory induced by sleep deprivation","authors":"Xiao Li , Qian Zheng , Honghong Yu , Tingting Du , Tian Hu , Lanyue Gao , Lihong Jia , Qi Sun","doi":"10.1016/j.neuroscience.2025.01.067","DOIUrl":"10.1016/j.neuroscience.2025.01.067","url":null,"abstract":"<div><div>Sleep plays an important role in the process of memory. This study investigated the role of the circadian clock gene, BMAL1 of the master circadian clock in mediating the impairment of hippocampus-dependent recognition memory caused by sleep deprivation. After 4 weeks of sleep deprivation, the novel object recognitiontask was used to evaluate the recognition memory of mice, the expression levels of circadian clock genes, and Nrf2 and PKA/CREB/BDNF signal pathways were detected by Western blot, Realtime-qPCR, and immunofluorescence. The mice in the SD group exhibited a significant decrease in the duration of exploration of novel objects. The protein expression levels of PER1, PER2, CLOCK, and BMAL1, and PKA/CREB/BDNF pathway in the hippocampus of the SD group were significantly reduced, and the Nrf2-mediated anti-oxidative capacity was also compromised in the SD group. Moreover, these aberrations could be mitigated through compensation with BMAL1 in the SCN of the hypothalamus. Sleep deprivation resulted in a reduction in the expression of the core clock gene BMAL1 in the hippocampus, leading to an imbalance in the antioxidant system and damaging down-regulating the PKA/CREB/BDNF signal pathway that related to the proteins associated with recognition memory in the hippocampal synapse plasticity and oxidative stress, which could be reversed by overexpression compensation of BMAL1 in the SCN that might rely on the multi-synaptic neural projections to the hippocampus.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"569 ","pages":"Pages 1-11"},"PeriodicalIF":2.9,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143104334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Behavior in both humans and animals is significantly influenced by the brain’s reward system. Many studies have shown that this dopaminergic system is the root of drug addiction and abuse. Melatonin, an indoleamine neurohormone, has been studied for its potential negative effects on addictive drugs such as morphine. This study evaluates the effect of intraventricular melatonin injection during different phases of morphine conditioning.
Method
Rats were conditioned with morphine [5 mg/kg; subcutaneously (SC)] for three days. The changes in conditioned place preference (CPP) scores following the injection of different doses of melatonin [25, 50, and 100 μg/kg; intracerebroventricular (ICV)] were investigated during the acquisition, expression, extinction, and reinstatement phases of morphine conditioning. After completing these steps, the c-Fos level in the nucleus accumbens (NAc) was measured using the ELISA technique.
Result
The results indicated that daily injections of 50 and 100 μg/kg melatonin during the acquisition and expression phases caused a dose-dependent decrease in the conditioning score. During the extinction phase, melatonin administration reduced its duration incrementally. Notably, only the 100 μg/kg dose significantly decreased morphine reinstatement. In terms of c-Fos levels, which were elevated after morphine consumption, melatonin administration led to a significant reduction across all phases.
Conclusion
This study demonstrates the neural interaction between melatonin and the opioid system. The evidence suggests that melatonin may be effective at decreasing drug-related rewards and has potential utility in preventing addiction.
{"title":"The effect of intracerebroventricular injection of melatonin on the period of acquisition, expression, extinction, and reinstatement of morphine conditioned place preference in the male rat: A behavioral and biochemical study","authors":"Hafez Yadi , Bahareh Soleimanpourian , Shayan Gooran , Amirhossein Momeni , Nourollah Rezaei , Ali Siahposht-Khachaki , Saeid Bagheri-Mohammadi","doi":"10.1016/j.neuroscience.2025.01.066","DOIUrl":"10.1016/j.neuroscience.2025.01.066","url":null,"abstract":"<div><h3>Background</h3><div>Behavior in both humans and animals is significantly influenced by the brain’s reward system. Many studies have shown that this dopaminergic system is the root of drug addiction and abuse. Melatonin, an indoleamine neurohormone, has been studied for its potential negative effects on addictive drugs such as morphine. This study evaluates the effect of intraventricular melatonin injection during different phases of morphine conditioning.</div></div><div><h3>Method</h3><div>Rats were conditioned with morphine [5 mg/kg; subcutaneously (SC)] for three days. The changes in conditioned place preference (CPP) scores following the injection of different doses of melatonin [25, 50, and 100 μg/kg; intracerebroventricular (ICV)] were investigated during the acquisition, expression, extinction, and reinstatement phases of morphine conditioning. After completing these steps, the c-Fos level in the nucleus accumbens (NAc) was measured using the ELISA technique.</div></div><div><h3>Result</h3><div>The results indicated that daily injections of 50 and 100 μg/kg melatonin during the acquisition and expression phases caused a dose-dependent decrease in the conditioning score. During the extinction phase, melatonin administration reduced its duration incrementally. Notably, only the 100 μg/kg dose significantly decreased morphine reinstatement. In terms of c-Fos levels, which were elevated after morphine consumption, melatonin administration led to a significant reduction across all phases.</div></div><div><h3>Conclusion</h3><div>This study demonstrates the neural interaction between melatonin and the opioid system. The evidence suggests that melatonin may be effective at decreasing drug-related rewards and has potential utility in preventing addiction.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"569 ","pages":"Pages 21-31"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.neuroscience.2025.01.065
William Almaguer-Melian , Daymara Mercerón-Martínez , Laura Alacán-Ricardo , Arturo Ernesto Vergara Piña , Changchi Hsieh , Jorge A. Bergado-Rosado , Todd Charlton Sacktor
Although many studies have addressed the role of the amygdala in modulating long-term memory, it is not known whether weak training plus amygdala stimulation can transform a short-term memory into a remote memory. Object place recognition (OPR) memory after strong training remains hippocampus-dependent through the persistent action of protein kinase Mzeta (PKMζ) for at least 6 days, but it is unknown whether weak training plus amygdala stimulation can transform short-term memory into an even longer memory, and whether such memory is stored through more persistent action of PKMζ in hippocampus. We trained male rats (150 total in our study) to acquire OPR and 15 min or 5 h later induced a brief pattern of electrical stimulation in basolateral amygdala (BLA). Our results reveal that a short-term memory lasting < 4h can be converted into remote memory lasting at least 3 weeks if the BLA is activated 15 min, but not 5 h after learning. To examine how this remote memory is maintained, we injected ZIP, an inhibitor of atypical protein kinase Cs (aPKCs), PKMζ and PKCι/λ, into either hippocampal CA1, dentate gyrus (DG), or anterior cingulate cortex (ACC). Our data reveal amygdala stimulation produces consolidation into remote memory, not by persistent aPKC activation in the hippocampal formation, but in ACC. Our data establish a powerful modulating role of the BLA in forming remote memory and open a path in the search for neurological restoration of memory, based on enhancing synaptic plasticity in aging or neurodegenerative disorders such as Alzheimer’s disease.
{"title":"Amygdala stimulation transforms short-term memory into remote memory by persistent activation of atypical protein kinase C in the anterior cingulate cortex","authors":"William Almaguer-Melian , Daymara Mercerón-Martínez , Laura Alacán-Ricardo , Arturo Ernesto Vergara Piña , Changchi Hsieh , Jorge A. Bergado-Rosado , Todd Charlton Sacktor","doi":"10.1016/j.neuroscience.2025.01.065","DOIUrl":"10.1016/j.neuroscience.2025.01.065","url":null,"abstract":"<div><div>Although many studies have addressed the role of the amygdala in modulating long-term memory, it is not known whether weak training plus amygdala stimulation can transform a short-term memory into a remote memory. Object place recognition (OPR) memory after strong training remains hippocampus-dependent through the persistent action of protein kinase Mzeta (PKMζ) for at least 6 days, but it is unknown whether weak training plus amygdala stimulation can transform short-term memory into an even longer memory, and whether such memory is stored through more persistent action of PKMζ in hippocampus. We trained male rats (150 total in our study) to acquire OPR and 15 min or 5 h later induced a brief pattern of electrical stimulation in basolateral amygdala (BLA). Our results reveal that a short-term memory lasting < 4h can be converted into remote memory lasting at least 3 weeks if the BLA is activated 15 min, but not 5 h after learning. To examine how this remote memory is maintained, we injected ZIP, an inhibitor of atypical protein kinase Cs (aPKCs), PKMζ and PKCι/λ, into either hippocampal CA1, dentate gyrus (DG), or anterior cingulate cortex (ACC). Our data reveal amygdala stimulation produces consolidation into remote memory, not by persistent aPKC activation in the hippocampal formation, but in ACC. Our data establish a powerful modulating role of the BLA in forming remote memory and open a path in the search for neurological restoration of memory, based on enhancing synaptic plasticity in aging or neurodegenerative disorders such as Alzheimer’s disease.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"569 ","pages":"Pages 288-297"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.neuroscience.2025.01.063
Timothy Daly
The call to synergize brain health with mental health has major ramifications for research and policy. Mental health has been recognized as a universal human right, but no such declaration exists for brain health. Here, I defend the right to lifelong brain health as a derived, intermediary, and generative right. It is derived from the right to physical health because it is reducible to facts about the health of the body. This grounds brain health in the right to physical health, a long-standing right with hard legal status, while avoiding “rights inflation.” It is intermediary because it bridges the gap between physical and mental health, since the brain is an organ that is central to both physical and mental health. It is generative because it provides impetus to downstream actions including the creation of health-based “neurorights” and bolstering the right to a healthy environment to protect collective cognitive health. Thus, the right to lifelong brain health would guarantee the right of citizens to live and grow in a brain health-promoting environment. A rights-based approach to brain health also has important consequences for research. It would help to move research away from the disease paradigm that focuses on individual risk and responsibility to the study of deeper contributions to brain health and disease through a population neuroscience approach to public brain health. Until the right to brain health is recognized alongside mental health, their synergy will remain incomplete, and brain health promotion will lack unity.
{"title":"Brain health is a human right: Implications for policy and research","authors":"Timothy Daly","doi":"10.1016/j.neuroscience.2025.01.063","DOIUrl":"10.1016/j.neuroscience.2025.01.063","url":null,"abstract":"<div><div>The call to synergize brain health with mental health has major ramifications for research and policy. Mental health has been recognized as a universal human right, but no such declaration exists for brain health. Here, I defend the right to lifelong brain health as a derived, intermediary, and generative right. It is derived from the right to physical health because it is reducible to facts about the health of the body. This grounds brain health in the right to physical health, a long-standing right with hard legal status, while avoiding “rights inflation.” It is intermediary because it bridges the gap between physical and mental health, since the brain is an organ that is central to both physical and mental health. It is generative because it provides impetus to downstream actions including the creation of health-based “neurorights” and bolstering the right to a healthy environment to protect collective cognitive health. Thus, the right to lifelong brain health would guarantee the right of citizens to live and grow in a brain health-promoting environment. A rights-based approach to brain health also has important consequences for research. It would help to move research away from the disease paradigm that focuses on individual risk and responsibility to the study of deeper contributions to brain health and disease through a population neuroscience approach to public brain health. Until the right to brain health is recognized alongside mental health, their synergy will remain incomplete, and brain health promotion will lack unity.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"569 ","pages":"Pages 147-154"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Transcranial direct current stimulation (tDCS) is an effective rehabilitation strategy that promotes motor learning. The related studies reported different findings through different modalities of tDCS over different brain regions. This study aimed to identify the optimal effects of tDCS on motor learning through a systematic review and network meta-analysis, focusing on determining the best electrode montage and assessing the efficacy of various tDCS configurations. The search was performed from PubMed, Scopus, and Web of Science databases from inception until April 15, 2022. Nineteen eligible studies were included in the study. The findings indicated that motor cortex (M1) a-tDCS and cerebellar a-tDCS significantly enhance motor learning (short-term and long-term efficacy on both parameters of motor learning; Response Time (RT) and Error Rate (ER)) more than posterior parietal cortex (PPC) a-tDCS (P < 0.5,0.65 to 90 % in SUCRA). Dual site tDCS enhances motor learning (efficacy on parameters of motor learning; RT and ER), with more efficacy as compared to unilateral tDCS (P < 0.05, 78 % to 84 % in SUCRA). In addition, the findings indicated that PPC a-tDCS has the least efficacy of motor learning as compared to the other tDCS interventions (P < 0.05, 0.5 % to 0.13 %). It is suggested that dual site tDCS and M1 or cerebellar a-tDCS be used, as compared to other tDCS interventions in other brain regions, for the improvement of motor learning.
{"title":"The effects of transcranial direct current stimulation montages on motor learning across various brain regions: A systematic review and network meta-analysis","authors":"Fatemeh Ehsani , Ahmad Jayedi , Fatemeh Motaharinezhad , Shapour Jaberzadeh","doi":"10.1016/j.neuroscience.2025.01.058","DOIUrl":"10.1016/j.neuroscience.2025.01.058","url":null,"abstract":"<div><div>Transcranial direct current stimulation (tDCS) is an effective rehabilitation strategy that promotes motor learning. The related studies reported different findings through different modalities of tDCS over different brain regions. This study aimed to identify the optimal effects of tDCS on motor learning through a systematic review and network <em>meta</em>-analysis, focusing on determining the best electrode montage and assessing the efficacy of various tDCS configurations. The search was performed from PubMed, Scopus, and Web of Science databases from inception until April 15, 2022. Nineteen eligible studies were included in the study. The findings indicated that motor cortex (M1) a-tDCS and cerebellar a-tDCS significantly enhance motor learning (short-term and long-term efficacy on both parameters of motor learning; Response Time (RT) and Error Rate (ER)) more than posterior parietal cortex (PPC) a-tDCS (P < 0.5,0.65 to 90 % in SUCRA). Dual site tDCS enhances motor learning (efficacy on parameters of motor learning; RT and ER), with more efficacy as compared to unilateral tDCS (P < 0.05, 78 % to 84 % in SUCRA). In addition, the findings indicated that PPC a-tDCS has the least efficacy of motor learning as compared to the other tDCS interventions (P < 0.05, 0.5 % to 0.13 %). It is suggested that dual site tDCS and M1 or cerebellar a-tDCS be used, as compared to other tDCS interventions in other brain regions, for the improvement of motor learning.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"569 ","pages":"Pages 32-42"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This study investigated the effect of a medium high-fat diet (HFD)-induced maternal obesity and gestational diabetes mellitus (GDM) on rat offspring to verify the hypothesis that maternal obesity and GDM cause brain pathologies and premature brain aging in the prefrontal cortex and hippocampus of the adolescent and early adult offspring. Maternal obesity and GDM were generated by a medium HFD and HFD combined with streptozotocin, respectively. Metabolic parameters were used to confirm the successful model in mothers. Systemic alterations and brain pathology were investigated in their adolescent and early adult offspring. During pregnancy, HFD-fed rats exhibited obesity, while GDM rats had hyperglycemia with insulin resistance. Offspring from high-fat diet dams (OHFD) had higher body weight when compared with offspring from normal diet dams (OND), while offspring from gestational diabetes mellitus dams (OGDM) had lower body weight than OHFD but comparable with OND. No significant alterations were found in glucose tolerance, systemic oxidative stress, and inflammation in the offspring. Additionally, neither adolescent nor early adult rats OHFD or OGDM developed brain pathologies or premature aging with no difference in oxidative stress, inflammation, mitochondrial dynamics, mitophagy, blood–brain barrier, synaptic plasticity, apoptosis, and aging markers among the offspring groups. Our results indicated that maternal obesity and GDM did not cause brain pathologies or premature brain aging at the adolescent and early adult stages of offspring in rats. Our study highlights the importance of maintaining a healthy diet in the offspring of obese and GDM mothers to keep healthy later in their lives.
{"title":"Mothers with obesity and gestational diabetes did not induce brain pathologies or premature brain aging in their adolescent and early adult offspring in rats","authors":"Huatuo Huang , Nattayaporn Apaijai , Chanisa Thonusin , Panan Suntornsaratoon , Nipon Chattipakorn , Narattaphol Charoenphandhu , Siriporn C. Chattipakorn","doi":"10.1016/j.neuroscience.2025.01.056","DOIUrl":"10.1016/j.neuroscience.2025.01.056","url":null,"abstract":"<div><div>This study investigated the effect of a medium high-fat diet (HFD)-induced maternal obesity and gestational diabetes mellitus (GDM) on rat offspring to verify the hypothesis that maternal obesity and GDM cause brain pathologies and premature brain aging in the prefrontal cortex and hippocampus of the adolescent and early adult offspring. Maternal obesity and GDM were generated by a medium HFD and HFD combined with streptozotocin, respectively. Metabolic parameters were used to confirm the successful model in mothers. Systemic alterations and brain pathology were investigated in their adolescent and early adult offspring. During pregnancy, HFD-fed rats exhibited obesity, while GDM rats had hyperglycemia with insulin resistance. Offspring from high-fat diet dams (OHFD) had higher body weight when compared with offspring from normal diet dams (OND), while offspring from gestational diabetes mellitus dams (OGDM) had lower body weight than OHFD but comparable with OND. No significant alterations were found in glucose tolerance, systemic oxidative stress, and inflammation in the offspring. Additionally, neither adolescent nor early adult rats OHFD or OGDM developed brain pathologies or premature aging with no difference in oxidative stress, inflammation, mitochondrial dynamics, mitophagy, blood–brain barrier, synaptic plasticity, apoptosis, and aging markers among the offspring groups. Our results indicated that maternal obesity and GDM did not cause brain pathologies or premature brain aging at the adolescent and early adult stages of offspring in rats. Our study highlights the importance of maintaining a healthy diet in the offspring of obese and GDM mothers to keep healthy later in their lives.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"568 ","pages":"Pages 454-464"},"PeriodicalIF":2.9,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rodent models of cerebral ischemia provide a valuable contribution to a better understanding of stroke pathophysiology, to validate diagnostic methods, and to enable testing of new treatments for ischemia-reperfusion damage and comorbidities. However, ethical concerns have led to increased attention to the welfare aspects of such models. Supportive therapies are an essential part of the overall animal care and use program and should be tailored to the experimental model being studied, the regulatory requirements, and research objectives to achieve high-quality preclinical studies and ethical research practices. On the other hand, the use of veterinary medical treatments in preclinical models of stroke must balance the needs of animal care and potential sources of bias in experimental results. This report provides a systematic review of the scientific literature covering the relevant period from years 1988 to September 2024, with the aim to investigating veterinary medical interventions useful to minimize suffering in rodent models of stroke without producing experimental bias. The research findings, consolidated from 181 selected studies, published from 1991 to 2023, indicate the feasibility of implementing personalized protocols of anesthesia, analgesics, antibiotics, and other supportive therapies in rodent models of stroke, while avoiding scientific interferences. These data fill a gap in current knowledge and could be of interest for an interdisciplinary audience working with rodent models of stroke, stimulating further refinements to safeguard both animal welfare and the validity of experimental findings, and may promote the culture of ethical conduct in various research fields and disciplines.
{"title":"Veterinary medical care in rodent models of stroke: Pitfalls and refinements to balance quality of science and animal welfare.","authors":"Sara Gargiulo, Sandra Albanese, Rosario Megna, Matteo Gramanzini, Gerardo Marsella, Lidovina Vecchiarelli","doi":"10.1016/j.neuroscience.2025.01.044","DOIUrl":"https://doi.org/10.1016/j.neuroscience.2025.01.044","url":null,"abstract":"<p><p>Rodent models of cerebral ischemia provide a valuable contribution to a better understanding of stroke pathophysiology, to validate diagnostic methods, and to enable testing of new treatments for ischemia-reperfusion damage and comorbidities. However, ethical concerns have led to increased attention to the welfare aspects of such models. Supportive therapies are an essential part of the overall animal care and use program and should be tailored to the experimental model being studied, the regulatory requirements, and research objectives to achieve high-quality preclinical studies and ethical research practices. On the other hand, the use of veterinary medical treatments in preclinical models of stroke must balance the needs of animal care and potential sources of bias in experimental results. This report provides a systematic review of the scientific literature covering the relevant period from years 1988 to September 2024, with the aim to investigating veterinary medical interventions useful to minimize suffering in rodent models of stroke without producing experimental bias. The research findings, consolidated from 181 selected studies, published from 1991 to 2023, indicate the feasibility of implementing personalized protocols of anesthesia, analgesics, antibiotics, and other supportive therapies in rodent models of stroke, while avoiding scientific interferences. These data fill a gap in current knowledge and could be of interest for an interdisciplinary audience working with rodent models of stroke, stimulating further refinements to safeguard both animal welfare and the validity of experimental findings, and may promote the culture of ethical conduct in various research fields and disciplines.</p>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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.neuroscience.2025.01.059
Jie Song, Aihemaitijiang Yusufu, Jiayu Sun, Hongyu Zhou, Hui Chen, Dun Liu, Qiyue Zhang, Li Li
Peripheral nerve injury disrupts communication between the primary motor cortex (M1) and the target muscle, leading to alterations in synaptic plasticity within the lesion projection zone (LPZ). While nerve repair holds the potential to restore this pathway and further modulate synaptic plasticity within the LPZ, the underlying mechanisms remain incompletely understood. In this study, we established a rat model with immediate repair following unilateral median nerve transection and categorized the functional recovery of the affected limb into three phases: the injury phase, recovery phase, and rehabilitation phase, corresponding to stages of muscle non-reinnervation, gradual reinnervation, and completed reinnervation, respectively. Our findings revealed that during these phases, excitatory synaptic transmission in M1 layer II/III pyramidal neurons initially decreases, then increases, and ultimately returns to baseline levels. Conversely, inhibitory synaptic transmission initially increases, then decreases, and remains reduced even after full peripheral recovery, accompanied by upregulation of inhibitory synaptic receptors. These findings suggest that excitatory and inhibitory synaptic plasticity play opposing roles in the nerve repair process, with excitatory plasticity primarily involved in short-term responses and inhibitory plasticity contributing to both short-term and long-term modulation.
{"title":"Dynamic changes of excitatory and inhibitory synapses in layer II/III of the primary motor cortex after peripheral nerve repair.","authors":"Jie Song, Aihemaitijiang Yusufu, Jiayu Sun, Hongyu Zhou, Hui Chen, Dun Liu, Qiyue Zhang, Li Li","doi":"10.1016/j.neuroscience.2025.01.059","DOIUrl":"https://doi.org/10.1016/j.neuroscience.2025.01.059","url":null,"abstract":"<p><p>Peripheral nerve injury disrupts communication between the primary motor cortex (M1) and the target muscle, leading to alterations in synaptic plasticity within the lesion projection zone (LPZ). While nerve repair holds the potential to restore this pathway and further modulate synaptic plasticity within the LPZ, the underlying mechanisms remain incompletely understood. In this study, we established a rat model with immediate repair following unilateral median nerve transection and categorized the functional recovery of the affected limb into three phases: the injury phase, recovery phase, and rehabilitation phase, corresponding to stages of muscle non-reinnervation, gradual reinnervation, and completed reinnervation, respectively. Our findings revealed that during these phases, excitatory synaptic transmission in M1 layer II/III pyramidal neurons initially decreases, then increases, and ultimately returns to baseline levels. Conversely, inhibitory synaptic transmission initially increases, then decreases, and remains reduced even after full peripheral recovery, accompanied by upregulation of inhibitory synaptic receptors. These findings suggest that excitatory and inhibitory synaptic plasticity play opposing roles in the nerve repair process, with excitatory plasticity primarily involved in short-term responses and inhibitory plasticity contributing to both short-term and long-term modulation.</p>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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.neuroscience.2025.01.060
Pin-Jing Zhang , Chen Luo , Jinli Chen , Jing Yang , Quan Wu , Lilong Chen , Hui Wang , Junfeng Wu , Hai-Feng Zhang
Hypertension is a common risk factors for ischemic stroke (IS), with the widely involvement of long non-coding RNAs (lncRNAs). The expression pattern and clinical significance of lncRNA PSMB8-AS1 was examined in essential hypertension (EH) patients with or without IS, as well as its role and mechanism in IS-induced neuron cell injury. Serum PSMB8-AS1 levels in 260 EH cases without IS and 280 participants with IS were detected via reverse transcription − quantitative polymerase chain reaction (RT-qPCR). The outcome during 12-month follow-up period was recorded. Receiver operating characteristic (ROC) curve and Kaplan − Meier (K-M) plot were drawn to evaluate diagnostic and prognostic values. HT22 cells were exposed to oxygen–glucose deprivation/reoxygenation (OGD/R) condition for cell function experiments. The cell viability, apoptosis, and inflammatory response were detected. Elevated expression of PSMB8-AS1 can differentiate IS from EH patients, and was independently related to the poor functional prognosis. Patients with high PSMB8-AS1 expression were likely to relapse during the 12-month follow-up period. In vitro, PSMB8-AS1 knockdown attenuated OGD/R-induced neuron cell apoptosis and inflammatory response, which was returned by microRNA-22-3p downregulation. PI3K-Akt signaling was of significance during the progress based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. PSMB8-AS1 acts as a novel biomarker for the diagnosis of IS in EH patients. Elevated PSMB8-AS1 is associated with worse neurological outcomes and higher recurrence rates of IS patients. LncRNA PSMB8-AS1 knockdown might have a promising role in attenuating OGD/R-induced neuron cell injury, that might be related to miR-22-3p.
{"title":"Clinical value and role of long non-coding RNA PSMB8-AS1 in the progress of ischemic stroke in patients with hypertension","authors":"Pin-Jing Zhang , Chen Luo , Jinli Chen , Jing Yang , Quan Wu , Lilong Chen , Hui Wang , Junfeng Wu , Hai-Feng Zhang","doi":"10.1016/j.neuroscience.2025.01.060","DOIUrl":"10.1016/j.neuroscience.2025.01.060","url":null,"abstract":"<div><div>Hypertension is a common risk factors for ischemic stroke (IS), with the widely involvement of long non-coding RNAs (lncRNAs). The expression pattern and clinical significance of lncRNA PSMB8-AS1 was examined in essential hypertension (EH) patients with or without IS, as well as its role and mechanism in IS-induced neuron cell injury. Serum PSMB8-AS1 levels in 260 EH cases without IS and 280 participants with IS were detected via reverse transcription − quantitative polymerase chain reaction (RT-qPCR). The outcome during 12-month follow-up period was recorded. Receiver operating characteristic (ROC) curve and Kaplan − Meier (K-M) plot were drawn to evaluate diagnostic and prognostic values. HT22 cells were exposed to oxygen–glucose deprivation/reoxygenation (OGD/R) condition for cell function experiments. The cell viability, apoptosis, and inflammatory response were detected. Elevated expression of PSMB8-AS1 can differentiate IS from EH patients, and was independently related to the poor functional prognosis. Patients with high PSMB8-AS1 expression were likely to relapse during the 12-month follow-up period. In vitro, PSMB8-AS1 knockdown attenuated OGD/R-induced neuron cell apoptosis and inflammatory response, which was returned by microRNA-22-3p downregulation. PI3K-Akt signaling was of significance during the progress based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. PSMB8-AS1 acts as a novel biomarker for the diagnosis of IS in EH patients. Elevated PSMB8-AS1 is associated with worse neurological outcomes and higher recurrence rates of IS patients. LncRNA PSMB8-AS1 knockdown might have a promising role in attenuating OGD/R-induced neuron cell injury, that might be related to miR-22-3p.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"569 ","pages":"Pages 114-122"},"PeriodicalIF":2.9,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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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