Neurobiology of Disease最新文献_第5页

An unraveled mystery: What's the role of brain sphingolipids in neurodegenerative and psychiatric disorders

IF 5.1 2区医学

Neurobiology of Disease Pub Date : 2025-02-20 DOI: 10.1016/j.nbd.2025.106852

Xintian Bie , Maoxing Zhang , Qingyu Wang , Ying Wang

{"title":"An unraveled mystery: What's the role of brain sphingolipids in neurodegenerative and psychiatric disorders","authors":"Xintian Bie , Maoxing Zhang , Qingyu Wang , Ying Wang","doi":"10.1016/j.nbd.2025.106852","DOIUrl":"10.1016/j.nbd.2025.106852","url":null,"abstract":"<div><div>Sphingolipids are a class of lipids highly expressed in brain, especially in the myelin sheath of white matter. In recent years, with the development of lipidomics, the role of brain sphingolipids in neurological disorders have raised lots of interests due to their function in neuronal signal transduction and survival. Although not thoroughly investigated, some previous studies have indicated that sphingolipids homeostasis are closely linked to the etiology and development of some neurological disorders. For example, disrupted sphingolipids level have been found in clinic patients with neurological disorders, such as neurodegeneration and psychiatric disorders. Conversely, intervention of sphingolipids metabolism by modulating activity of related enzymes also could result in pathological deficits identified in neurological disorders. Moreover, the alteration of sphingolipids catabolic pathway in the brain could be partly represented in cerebrospinal fluid and blood tissues, which show diagnostic potential for neurological disorders. Therefore, our review aims to summarize and discuss the known contents of bioactive sphingolipid metabolism with their related studies in neurodegenerative and psychiatric disorders, to help understand the potential mechanism underlying sphingolipid regulation of neural function and provide possible directions for further study. The new perspectives in this promising field will open up new therapeutic options for neurological disorders.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"207 ","pages":"Article 106852"},"PeriodicalIF":5.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143465065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Glycosphingolipids in neurodegeneration – Molecular mechanisms, cellular roles, and therapeutic perspectives

IF 5.1 2区医学

Neurobiology of Disease Pub Date : 2025-02-18 DOI: 10.1016/j.nbd.2025.106851

Andreas J. Hülsmeier

{"title":"Glycosphingolipids in neurodegeneration – Molecular mechanisms, cellular roles, and therapeutic perspectives","authors":"Andreas J. Hülsmeier","doi":"10.1016/j.nbd.2025.106851","DOIUrl":"10.1016/j.nbd.2025.106851","url":null,"abstract":"<div><div>Neurodegenerative diseases, including Alzheimer's (AD), Parkinson's (PD), Huntington's (HD), and amyotrophic lateral sclerosis (ALS), are characterized by progressive neuronal loss and pose significant global health challenges. Glycosphingolipids (GSLs), critical components of neuronal membranes, regulate signal transduction, membrane organization, neuroinflammation, and lipid raft functionality. This review explores GSL roles in neural development, differentiation, and neurogenesis, along with their dysregulation in neurodegenerative diseases. Aberrations in GSL metabolism drive key pathological features such as protein aggregation, neuroinflammation, and impaired signaling. Specific GSLs, such as GM1, GD3, and GM3, influence amyloid-beta aggregation in AD, α-synuclein stability in PD, and mutant huntingtin toxicity in HD. Therapeutic strategies targeting GSL metabolism, such as GM1 supplementation and enzyme modulation, have demonstrated potential to mitigate disease progression. Further studies using advanced lipidomics and glycomics may support biomarker identification and therapeutic advancements. This work aims to highlight the translational potential of GSL research for diagnosing and managing devastating neurodegenerative conditions.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"207 ","pages":"Article 106851"},"PeriodicalIF":5.1,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deficits in taste-guided behaviors and central processing of taste in the transgenic TDP-43Q331K mouse model of frontotemporal dementia

IF 5.1 2区医学

Neurobiology of Disease Pub Date : 2025-02-18 DOI: 10.1016/j.nbd.2025.106850

Camelia Yuejiao Zheng , Jennifer M. Blackwell , Alfredo Fontanini

{"title":"Deficits in taste-guided behaviors and central processing of taste in the transgenic TDP-43Q331K mouse model of frontotemporal dementia","authors":"Camelia Yuejiao Zheng , Jennifer M. Blackwell , Alfredo Fontanini","doi":"10.1016/j.nbd.2025.106850","DOIUrl":"10.1016/j.nbd.2025.106850","url":null,"abstract":"<div><div>Frontotemporal dementia (FTD) is the second most prevalent form of presenile dementia. Patients with FTD show prominent chemosensory symptoms such as abnormal detection and recognition thresholds for various gustatory stimuli. The chemosensory symptoms of FTD may be related to damage of the gustatory insular cortex (GC) as the insular cortex is one of the primary targets in FTD disease progression. Little is known about how circuitry changes in GC lead to deficits in taste processing in FTD. Here we tested the hypothesis that gustatory deficits are present in a mouse model of FTD, and that they are related to abnormal patterns of neural activity in GC. We behaviorally evaluated a transgenic FTD mouse model overexpressing human TDP-43 with a Q331K mutation (TDP-43<sup>Q331K</sup>) in a brief access test and a taste-based two alternative forced choice (2AFC) task probing the ability to discriminate sucrose/NaCl mixtures. TDP-43<sup>Q331K</sup> mice showed abnormal sucrose consumption and an impaired ability to discriminate taste mixtures compared to non-transgenic control mice. To assess deficits in GC taste processing, we relied on electrophysiological recordings using chronically implanted tetrodes in alert TDP-43<sup>Q331K</sup> and non-transgenic control mice. The proportion of taste-selective neurons in TDP-43<sup>Q331K</sup> mice decreased over time compared to control mice. Similarly, encoding of chemosensory information and processing of taste palatability were impaired in TDP-43<sup>Q331K</sup> mice compared to control mice. Overall, these results demonstrate taste-related symptoms in a mouse model of FTD and provide evidence for altered taste processing in GC of TDP-43<sup>Q331K</sup> mice compared to control mice.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"207 ","pages":"Article 106850"},"PeriodicalIF":5.1,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143454159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PYK2 in the dorsal striatum of Huntington's disease R6/2 mouse model

IF 5.1 2区医学

Neurobiology of Disease Pub Date : 2025-02-17 DOI: 10.1016/j.nbd.2025.106840

Omar Al Massadi , Mélody Labarchède , Benoit de Pins , Sophie Longueville , Albert Giralt , Theano Irinopoulou , Mythili Savariradjane , Enejda Subashi , Silvia Ginés , Jocelyne Caboche , Louise-Laure Mariani , Sandrine Betuing , Jean-Antoine Girault

{"title":"PYK2 in the dorsal striatum of Huntington's disease R6/2 mouse model","authors":"Omar Al Massadi , Mélody Labarchède , Benoit de Pins , Sophie Longueville , Albert Giralt , Theano Irinopoulou , Mythili Savariradjane , Enejda Subashi , Silvia Ginés , Jocelyne Caboche , Louise-Laure Mariani , Sandrine Betuing , Jean-Antoine Girault","doi":"10.1016/j.nbd.2025.106840","DOIUrl":"10.1016/j.nbd.2025.106840","url":null,"abstract":"<div><div>Huntington's disease (HD) is a devastating disease due to autosomal dominant mutation in the <em>HTT</em> gene. Its pathophysiology involves multiple molecular alterations including transcriptional defects. We previously showed that in HD patients and mouse model, the protein levels of the non-receptor tyrosine kinase PYK2 were decreased in the hippocampus and that viral expression of PYK2 improved the hippocampal phenotype. Here, we investigated the possible contribution of PYK2 in the striatum, a brain region particularly altered in HD. PYK2 mRNA levels were decreased in the striatum and hippocampus of R6/2 mice, a severe HD model. Striatal PYK2 protein levels were also decreased in R6/2 mice and human patients. PYK2 knockout by itself did not result in motor symptoms observed in HD mouse models. We examined whether PYK2 deficiency participated in the R6/2 mice phenotype by expressing PYK2 in their dorsal striatum using AAV vectors. With an AAV1/<em>Camk2a</em> promoter, we did not observe significant improvement of body weight, clasping, motor activity and coordination (rotarod) alterations observed in R6/2 mice. With an AAV9/<em>SYN1</em> promoter we found a slightly higher body weight and a trend to better rotarod performance. Both viruses similarly transduced striatal projection neurons and somatostatin-positive interneurons but only AAV9/<em>SYN1</em> led to PYK2 expression in cholinergic and parvalbumin-positive interneurons. Expression of PYK2 in cholinergic interneurons may contribute to the slight effects observed. We conclude that PYK2 mRNA and protein levels are decreased in the striatum as in hippocampus of HD patients and mouse models. However, in contrast to hippocampus, striatal viral expression of PYK2 has only a minor effect on the R6/2 model striatal phenotype.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"207 ","pages":"Article 106840"},"PeriodicalIF":5.1,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The projection from the rostral anterior cingulate cortex to the ventral tegmental area regulates 5-HT-induced itch aversion and scratching in rats

IF 5.1 2区医学

Neurobiology of Disease Pub Date : 2025-02-15 DOI: 10.1016/j.nbd.2025.106844

Jun-Fei Teng , Xing-Yu Lu , Jun-Hui Long , Ying Shi , Xue-Qiang Hu , Jian-Feng Sui , Ping Wang , Lian-Lin Zeng , Xuan Li , Jin-He Xu , Zu-Zhen Ou , Ke-Hui Hu , Shu-Lei Liu

{"title":"The projection from the rostral anterior cingulate cortex to the ventral tegmental area regulates 5-HT-induced itch aversion and scratching in rats","authors":"Jun-Fei Teng , Xing-Yu Lu , Jun-Hui Long , Ying Shi , Xue-Qiang Hu , Jian-Feng Sui , Ping Wang , Lian-Lin Zeng , Xuan Li , Jin-He Xu , Zu-Zhen Ou , Ke-Hui Hu , Shu-Lei Liu","doi":"10.1016/j.nbd.2025.106844","DOIUrl":"10.1016/j.nbd.2025.106844","url":null,"abstract":"<div><div>Many studies in humans and rodents have shown that the anterior cingulate cortex (ACC) plays a critical role in the regulation of pain-related aversion and that the projection from the rostral ACC (rACC) to the ventral tegmental area (VTA) is implicated in this modulation process. The ACC is also reported to be involved in the regulation of itch-scratch behavior. However, it remains unclear whether the ACC is involved in the modulation of the negative emotions induced by acute itch sensation. In this study, we investigated the pruritogen-induced conditioned place aversion (CPA) and itch-scratching behavior in rats after pharmacogenetic inhibition of the activities of rACC-VTA pathway or the rACC neurons, respectively. Pharmacogenetic inhibition of glutamatergic neurons of rACC projecting to the VTA alleviated the CPA responses and itch-scratching behavior induced by the subcutaneous injection of 5-HT, a nonhistamine-dependent pruritogen. However, pharmacogenetic inhibition of rACC neurons did not change the CPA behavior associated with itch and, conversely, increased itch-scratching behavior. These results reveal that a specific subpopulation of rACC neurons projecting to the VTA positively regulates itch sensation and the negative emotion accompanying itch, whereas the global rACC negatively modulates acute non-histaminergic itch in rats. Postsynaptic GABAergic neurons in the VTA may mediate emotion modulation of the rACC-VTA pathway. The current findings contribute to a better understanding of the circuit mechanisms underlying the processing of different components of itch, such as sensation and emotion.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"207 ","pages":"Article 106844"},"PeriodicalIF":5.1,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A missense variant in DEPDC5 resulted in abnormal morphology and increased seizure susceptibility and mortality through regulating mTOR signaling

IF 5.1 2区医学

Neurobiology of Disease Pub Date : 2025-02-13 DOI: 10.1016/j.nbd.2025.106842

Jie Liu , Rui Huang , Fenglin Tang , Yuanlin Ma , Patrick Kwan

{"title":"A missense variant in DEPDC5 resulted in abnormal morphology and increased seizure susceptibility and mortality through regulating mTOR signaling","authors":"Jie Liu , Rui Huang , Fenglin Tang , Yuanlin Ma , Patrick Kwan","doi":"10.1016/j.nbd.2025.106842","DOIUrl":"10.1016/j.nbd.2025.106842","url":null,"abstract":"<div><div>Dishevelled, Egl-10 and Pleckstrin domain-containing 5 (<em>DEPDC5)</em>, a key inhibitor of the mammalian/mechanistic target of rapamycin (mTOR) pathway, is frequently associated with epilepsy. However, the functional consequences of most <em>DEPDC5</em> variants rely on in silico predictions and have not been experimentally confirmed.This study aimed to determine the functional consequences of a <em>DEPDC5</em> variant identified in patients with epilepsy across multiple generations in a Chinese family. We identified a missense heterozygous variant (c. 2055C > A; p. Phe685Leu) in <em>DEPDC5</em> in Chinese family affected by epilepsy across three generations. This variant has not been previously reported in the Chinese population. Primary neuron cultures transfected with the mutant plasmid exhibited altered subcellular localization. To explore the mechanisms of epilepsy linked to this variant, we created nervous system-specific conditional human <em>DEPDC5</em> knock-in mouse using Cre-recombination under the Nestin promotor (h<em>DEPDC5</em><sup>WT</sup> mice, h<em>DEPDC5</em><sup>F685L</sup> mice). Compared to wildtype (WT) and h<em>DEPDC5</em><sup>WT</sup> mice, h<em>DEPDC5</em><sup>F685L</sup> mice exhibited histological signs of mTOR hyperactivation, enlarged neuronal soma, abnormal neurons, and heightened susceptibility to seizures and mortality. Administering rapamycin to h<em>DEPDC5</em><sup>F685L</sup> mice starting two weeks after birth normalized neuronal size and mTOR activity, decreased seizure susceptibility and mortality, and showed no effects in the WT or h<em>DEPDC5</em><sup>WT</sup> mice. Collectively, these results indicate that the <em>DEPDC5</em> variant causes abnormal morphology and increased seizure vulnerability through modulation of mTOR signaling.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"207 ","pages":"Article 106842"},"PeriodicalIF":5.1,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lack of neuroprotection after systemic administration of the soluble TNF inhibitor XPro1595 in an rAAV6-α-Syn + PFFs-induced rat model for Parkinson's disease

IF 5.1 2区医学

Neurobiology of Disease Pub Date : 2025-02-13 DOI: 10.1016/j.nbd.2025.106841

Filip Fredlund , Claes Fryklund , Olivia Trujeque-Ramos , Hannah A. Staley , Joaquin Pardo , Kelvin C. Luk , Malú G. Tansey , Maria Swanberg

{"title":"Lack of neuroprotection after systemic administration of the soluble TNF inhibitor XPro1595 in an rAAV6-α-Syn + PFFs-induced rat model for Parkinson's disease","authors":"Filip Fredlund , Claes Fryklund , Olivia Trujeque-Ramos , Hannah A. Staley , Joaquin Pardo , Kelvin C. Luk , Malú G. Tansey , Maria Swanberg","doi":"10.1016/j.nbd.2025.106841","DOIUrl":"10.1016/j.nbd.2025.106841","url":null,"abstract":"<div><div>Parkinson's disease (PD) is characterized by dopaminergic neurodegeneration, α-Synuclein (α-Syn) pathology, and inflammation. Microglia in the substantia nigra pars compacta (SNpc) upregulate major histocompatibility complex class II (MHCII), and variants in genes encoding MHCII affect PD risk. Additionally, elevated TNF levels and α-Syn-reactive T cells in circulation suggest a strong link between innate and adaptive immune responses in PD. We have previously reported that reduced levels of the class II transactivator, the master regulator of MHCII expression, increases susceptibility to α-Syn-induced PD-like pathology in rats and are associated with higher serum levels of soluble TNF (sTNF). Here, we demonstrate that inhibiting sTNF with a dominant-negative TNF variant, XPro1595, known to be neuroprotective in endotoxin- and toxin-induced neurodegeneration models, fails to protect against robust α-Syn-induced PD-like pathology in rats. We used a model combining rAAV-mediated α-Syn overexpression in SNpc with striatal injection of α-Syn preformed fibrils two weeks later. Systemic XPro1595 treatment was initiated one-week post-rAAV-α-Syn. We observed up to 70 % loss of striatal dopaminergic fibers without treatment, and no protective effects on dopaminergic neurodegeneration after XPro1595 administration. Pathological α-Syn levels as well as microglial and astrocytic activation were not reduced in SNpc or striatum following XPro1595 treatment. An increase in IL-6 and IL-1β levels in CSF was observed in rats treated with XPro1595, possibly explaining a lack of protective effects following treatment. Our results highlight the need to determine the importance of timing of treatment initiation, which is crucial for future applications of sTNF therapies in PD patients.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"207 ","pages":"Article 106841"},"PeriodicalIF":5.1,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Long-term exposure to anti-GluA3 antibodies triggers functional and structural changes in hippocampal neurons

IF 5.1 2区医学

Neurobiology of Disease Pub Date : 2025-02-13 DOI: 10.1016/j.nbd.2025.106843

Maria Italia , Alessio Spinola , Barbara Borroni , Monica DiLuca , Fabrizio Gardoni

{"title":"Long-term exposure to anti-GluA3 antibodies triggers functional and structural changes in hippocampal neurons","authors":"Maria Italia , Alessio Spinola , Barbara Borroni , Monica DiLuca , Fabrizio Gardoni","doi":"10.1016/j.nbd.2025.106843","DOIUrl":"10.1016/j.nbd.2025.106843","url":null,"abstract":"<div><div>Autoantibodies targeting the GluA3 subunit of AMPA receptors (AMPARs) are implicated in various neurological disorders, including Rasmussen's encephalitis, epilepsy, and frontotemporal dementia. However, their precise role in disease pathology remains insufficiently understood. This study investigated the long-term effects of human anti-GluA3 antibodies (anti-GluA3 hIgGs) on neuronal morphology and function using primary rat hippocampal neurons. We found that long-term exposure to anti-GluA3 hIgGs leads to the delocalisation of GluA3-containing AMPARs at extrasynaptic sites. This molecular event is correlated to dendritic arbor reorganisation, characterised by increased complexity near the soma and progressive simplification in distal regions as well as an increase in the number of shorter dendrites and a corresponding loss of longer ones, thus suggesting altered dendritic pruning dynamics. The altered neuronal architecture was accompanied by an increase in the number of dendritic spines and a modification of their morphology, indicating relevant changes in synaptic connectivity. Functionally, anti-GluA3 hIgGs significantly enhanced NMDA receptor-mediated postsynaptic Ca<sup>2+</sup> currents and increased nuclear levels of phosphorylated cAMP response element-binding protein (CREB), indicating altered signal transduction. Overall, our study provides critical insights into the role of anti-GluA3 hIgGs in disease and potentially identifies new therapeutic targets for pathological conditions where they are present.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"207 ","pages":"Article 106843"},"PeriodicalIF":5.1,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The impact of gut microbiota on the occurrence, treatment, and prognosis of ischemic stroke

IF 5.1 2区医学

Neurobiology of Disease Pub Date : 2025-02-12 DOI: 10.1016/j.nbd.2025.106836

Liying Chen , Xi Wang , Shiqi Wang , Weili Liu , Zhangyong Song , Huiling Liao

{"title":"The impact of gut microbiota on the occurrence, treatment, and prognosis of ischemic stroke","authors":"Liying Chen , Xi Wang , Shiqi Wang , Weili Liu , Zhangyong Song , Huiling Liao","doi":"10.1016/j.nbd.2025.106836","DOIUrl":"10.1016/j.nbd.2025.106836","url":null,"abstract":"<div><div>Ischemic stroke (IS) is a cerebrovascular disease that predominantly affects middle-aged and elderly populations, exhibiting high mortality and disability rates. At present, the incidence of IS is increasing annually, with a notable trend towards younger affected individuals. Recent discoveries concerning the “gut-brain axis” have established a connection between the gut and the brain. Numerous studies have revealed that intestinal microbes play a crucial role in the onset, progression, and outcomes of IS. They are involved in the entire pathophysiological process of IS through mechanisms such as chronic inflammation, neural regulation, and metabolic processes. Although numerous studies have explored the relationship between IS and intestinal microbiota, comprehensive analyses of specific microbiota is relatively scarce. Therefore, this paper provides an overview of the typical changes in gut microbiota following IS and investigates the role of specific microorganisms in this context. Additionally, it presents a comprehensive analysis of post-stroke microbiological therapy and the relationship between IS and diet. The aim is to identify potential microbial targets for therapeutic intervention, as well as to highlight the benefits of microbiological therapies and the significance of dietary management. Overall, this paper seeks to provide key strategies for the treatment and management of IS, advocating for healthy diets and health programs for individuals. Meanwhile, it may offer a new perspective on the future interdisciplinary development of neurology, microbiology and nutrition.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"207 ","pages":"Article 106836"},"PeriodicalIF":5.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Attenuated neurotoxicity after repeated methamphetamine binges linked to dopamine transporter (DAT) decline 甲基苯丙胺反复酗酒后神经毒性减弱与多巴胺转运体（DAT）下降有关。

IF 5.1 2区医学

Neurobiology of Disease Pub Date : 2025-02-12 DOI: 10.1016/j.nbd.2025.106839

Noelia Granado , Liliana Mendieta , Yousef Tizabi , Mario Gustavo Murer , Rosario Moratalla

{"title":"Attenuated neurotoxicity after repeated methamphetamine binges linked to dopamine transporter (DAT) decline","authors":"Noelia Granado , Liliana Mendieta , Yousef Tizabi , Mario Gustavo Murer , Rosario Moratalla","doi":"10.1016/j.nbd.2025.106839","DOIUrl":"10.1016/j.nbd.2025.106839","url":null,"abstract":"<div><div>Methamphetamine (METH) abuse increases worldwide. In addition to its acute life-threatening effects, METH is toxic for dopaminergic neurons, increasing the risk of developing Parkinson's disease. The impact of repeated METH binge consumption on dopaminergic and neurotoxicity markers remains unclear. We exposed mice to a repeated “binge-like” METH regime, consisting of three doses over a 6 h interval, repeated three times with 14-day intervals. After the first binge, spontaneous motor activity decreased markedly but remained normal after subsequent binges. Following the first binge, we observed a 25 % loss of nigral dopaminergic cell bodies and significant axon terminal damage as assessed through striatal silver staining, with minimal further degeneration after additional binges. Dopaminergic markers were substantially depleted after the first and second binges, despite partial recovery between binges, dropping to below 20 % of control levels. By one day after the third binge, tyrosine hydroxylase (TH) and vesicular monoamine transporter 2 (VMAT2) stabilized at 50–60 % of control levels, but the dopamine transporter (DAT) remained at only 25 %, showing less recovery. These changes were accompanied by an evolving neuroinflammation pattern, with a transient microglial surge after the first binge and persistent astroglial and temperature responses. Overall, our findings indicate partial recovery of dopaminergic markers and the development of tolerance to METH neurotoxicity. The robust reduction of DAT after the first binge may contribute to this tolerance to subsequence binges by limiting METH entry into neurons thereby mitigating its neurotoxic effects.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"207 ","pages":"Article 106839"},"PeriodicalIF":5.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0