Progress in Neurobiology最新文献_第5页

PDGFR mediates lumbar spinal stenosis-induced neuropathic pain by regulating JAK2/STAT3 signaling in activated macrophages PDGFR通过调节活化巨噬细胞中JAK2/STAT3信号通路介导腰椎狭窄性神经性疼痛。

IF 6.1 2区医学

Progress in Neurobiology Pub Date : 2025-10-01 Epub Date: 2025-09-04 DOI: 10.1016/j.pneurobio.2025.102822

Kyung Jin Seo , Chan Sol Park , Mi So Park , Won Ho Na , Jee Youn Lee , Tae Young Yune

{"title":"PDGFR mediates lumbar spinal stenosis-induced neuropathic pain by regulating JAK2/STAT3 signaling in activated macrophages","authors":"Kyung Jin Seo , Chan Sol Park , Mi So Park , Won Ho Na , Jee Youn Lee , Tae Young Yune","doi":"10.1016/j.pneurobio.2025.102822","DOIUrl":"10.1016/j.pneurobio.2025.102822","url":null,"abstract":"<div><div>Lumbar spinal stenosis (LSS) is one of the most common spinal disorders in elderly people and is often accompanied by neuropathic pain. Although our previous studies have demonstrated that infiltrating macrophage contribute to chronic neuropathic pain in LSS rat model, the molecular mechanisms underlying macrophage activation and infiltration have not been fully elucidated. In this study, we examined the critical role of platelet-derived growth factor receptor (PDGFR) signaling pathway in neuropathic pain associated with macrophage infiltration and activation in LSS rats. The LSS rat model was induced by cauda equina compression using a silicone block placed within the epidural spaces of the L5-L6 vertebrae, with neuropathic pain developing four weeks after compression. We found that the PDGFR and Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathways were upregulated in infiltrated macrophages at 28 days in the LSS model. Administration of the PDGFR inhibitor imatinib significantly alleviated LSS-induced macrophages activation and infiltration. Imatinib also reduced LSS-induced chronic mechanical allodynia and inhibited the expression of inflammatory mediators including tumor necrosis factor alpha (TNF-α), interleukin beta (IL-1β), interleukin 6 (IL-6), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS). Furthermore, imatinib significantly alleviated the activation of RAW 264.7 macrophage cell line by lipopolysaccharide (LPS). These findings suggest that PDGFR signaling mediates neuropathic pain by promoting macrophage infiltration and activation following cauda equina compression and may serve as a potential therapeutic target for neuropathic pain in LSS patients.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"253 ","pages":"Article 102822"},"PeriodicalIF":6.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Rodent models of Alzheimer's disease: Critical analysis of current hypotheses and pathways for future research 阿尔茨海默病的啮齿动物模型：对当前假设和未来研究途径的批判性分析

IF 6.1 2区医学

Progress in Neurobiology Pub Date : 2025-09-01 Epub Date: 2025-08-29 DOI: 10.1016/j.pneurobio.2025.102821

Pasindu Hansana Singhaarachchi , Peter Antal , Frédéric Calon , Carsten Culmsee , Jean-Christophe Delpech , Martin Feldotto , Jorine Geertsema , Emmy E. Hoeksema , Aniko Korosi , Sophie Layé , Jonathan McQualter , Susanne R. de Rooij , Christoph Rummel , Mary Slayo , Luba Sominsky , Sarah J. Spencer

{"title":"Rodent models of Alzheimer's disease: Critical analysis of current hypotheses and pathways for future research","authors":"Pasindu Hansana Singhaarachchi , Peter Antal , Frédéric Calon , Carsten Culmsee , Jean-Christophe Delpech , Martin Feldotto , Jorine Geertsema , Emmy E. Hoeksema , Aniko Korosi , Sophie Layé , Jonathan McQualter , Susanne R. de Rooij , Christoph Rummel , Mary Slayo , Luba Sominsky , Sarah J. Spencer","doi":"10.1016/j.pneurobio.2025.102821","DOIUrl":"10.1016/j.pneurobio.2025.102821","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) was first described over a century ago. However, the mechanisms underlying the disease are not well understood to this day. This has negatively impacted our ability to create animal models to design and test targeted reliable treatments for the disease. Amyloid β plaque accumulation, aggregation of neurofibrillary tangles, neuroinflammation, neurodegeneration, and, of course, cognitive decline, are few of the many observed pathological features associated with AD. However, there is a concern that the animal models of AD that are based on these frameworks may not be accurately representing AD in people. As such, the results from preclinical trials have not historically translated well to the clinic. In this article, we review the current major hypotheses to describe AD; we outline the major strengths and weaknesses of the commonly used rodent models used to replicate features of these hypotheses; and we provide a strategy for the field for future research.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"252 ","pages":"Article 102821"},"PeriodicalIF":6.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144925331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cortical hyperexcitability drives dying forward amyotrophic lateral sclerosis symptoms and pathology in mice 小鼠皮质亢进性驱动垂死肌萎缩侧索硬化症的症状和病理。

IF 6.1 2区医学

Progress in Neurobiology Pub Date : 2025-09-01 Epub Date: 2025-08-08 DOI: 10.1016/j.pneurobio.2025.102809

Mouna Haidar , Aida Viden , Christin Daniel , Brittany Cuic , Taide Wang , Marius Rosier , Doris Tomas , Samuel A. Mills , Alistair Govier-Cole , Elvan Djouma , Nirma D. Perera , Sophia Luikinga , Valeria Rytova , Samantha K. Barton , David G. Gonsalvez , Lucy M. Palmer , Catriona McLean , Matthew C. Kiernan , Steve Vucic , Bradley J. Turner

{"title":"Cortical hyperexcitability drives dying forward amyotrophic lateral sclerosis symptoms and pathology in mice","authors":"Mouna Haidar , Aida Viden , Christin Daniel , Brittany Cuic , Taide Wang , Marius Rosier , Doris Tomas , Samuel A. Mills , Alistair Govier-Cole , Elvan Djouma , Nirma D. Perera , Sophia Luikinga , Valeria Rytova , Samantha K. Barton , David G. Gonsalvez , Lucy M. Palmer , Catriona McLean , Matthew C. Kiernan , Steve Vucic , Bradley J. Turner","doi":"10.1016/j.pneurobio.2025.102809","DOIUrl":"10.1016/j.pneurobio.2025.102809","url":null,"abstract":"<div><div>Degeneration of both upper motor neurons in the brain and lower motor neurons in the spinal cord defines amyotrophic lateral sclerosis (ALS), but how they are linked in ALS pathophysiology is unclear. Here, we uncover a cortical origin of neurodegeneration in ALS mediated by upper motor neuron hyperexcitability. Chronic hyperexcitability of upper motor neurons induced by excitatory chemogenetics in healthy adult mice induced progressive motor deficits, weakness and core pathological hallmarks of ALS, including upper motor neurons loss, synaptic pathology, corticospinal tract degeneration and reactive gliosis. Importantly, upper motor neuron hyperexcitability and loss were sufficient to drive degeneration of lower motor neurons and their distal axons and neuromuscular junctions, associated with astrocyte and microglial activation in spinal cord. Cortical hyperexcitability also triggered cytoplasmic TAR DNA binding protein 43 (TDP-43) aggregation in upper motor neurons and lower motor neurons, placing hyperexcitability upstream of TDP-43 proteinopathy in ALS. These findings establish a cortical origin of ALS mediated by upper motor neurons, consistent with an anterograde mechanism of neurodegeneration throughout the central and peripheral nervous systems.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"252 ","pages":"Article 102809"},"PeriodicalIF":6.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144817410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bidirectional control of generalized absence epilepsy networks via real-time direct depolarization of thalamocortical neurons 通过丘脑皮质神经元实时直接去极化双向控制广泛性缺失癫痫网络。

IF 6.1 2区医学

Progress in Neurobiology Pub Date : 2025-09-01 Epub Date: 2025-05-06 DOI: 10.1016/j.pneurobio.2025.102774

Tatiana P. Morais , Hannah L. Taylor , Olivér Nagy , Ferenc Mátyás , Francois David , Vincenzo Crunelli , Magor L. Lőrincz

{"title":"Bidirectional control of generalized absence epilepsy networks via real-time direct depolarization of thalamocortical neurons","authors":"Tatiana P. Morais , Hannah L. Taylor , Olivér Nagy , Ferenc Mátyás , Francois David , Vincenzo Crunelli , Magor L. Lőrincz","doi":"10.1016/j.pneurobio.2025.102774","DOIUrl":"10.1016/j.pneurobio.2025.102774","url":null,"abstract":"<div><div>Absence seizures (ASs), characterized by bilateral spike-and-wave discharges (SWDs), are a hallmark of idiopathic generalized epilepsies. We investigated the role of thalamocortical (TC) neurons in the generation and termination of ASs using optogenetic techniques in freely behaving GAERS rats, a well-established AS model. We demonstrate that direct depolarization of ChR2-transfected TC neurons in the ventrobasal thalamic nuclei during quiet wakefulness (QW) reliably elicits ethosuximide-sensitive ASs that have similar duration and frequency to those of spontaneous ASs, while showing little and no effect during active wakefulness (AW) and slow wave sleep (SWS), respectively. Light-stimulation of TC neurons fails to elicit ASs during AW, QW and SWS in non-epileptic control (NEC) rats, whereas it could evoke short ASs in Wistar rats, prevalently during QW. Notably, brief light stimulation effectively halted ongoing spontaneous ASs in GAERS rats (i.e. both SWDs and immobility), immediately altering thalamic multi-unit activity from rhythmic to irregular firing, irrespective of the SWD phase at which it was delivered. These findings support the view that the excitability of cortico-thalamic-cortical network is highly behavioural state-dependent, with increased susceptibility to the induction of ASs during QW, thus questioning the necessity of low-threshold burst firing of TC neurons in the generation of these seizures. Moreover, they highlight the dual control of ASs by TC neurons, underscoring their potential as therapeutic targets for AS modulation.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"252 ","pages":"Article 102774"},"PeriodicalIF":6.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144043145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Auditory regulation of hippocampal locomotion circuits by a non-canonical reticulo-limbic pathway 非规范网状边缘通路对海马运动回路的听觉调节

IF 6.1 2区医学

Progress in Neurobiology Pub Date : 2025-09-01 Epub Date: 2025-08-14 DOI: 10.1016/j.pneurobio.2025.102811

Jessica Winne , George Nascimento , Rafael Pedrosa , Margareth Nogueira , Cristiano S. Simões , Klas Kullander , Katarina E. Leão , Richardson N. Leão

{"title":"Auditory regulation of hippocampal locomotion circuits by a non-canonical reticulo-limbic pathway","authors":"Jessica Winne , George Nascimento , Rafael Pedrosa , Margareth Nogueira , Cristiano S. Simões , Klas Kullander , Katarina E. Leão , Richardson N. Leão","doi":"10.1016/j.pneurobio.2025.102811","DOIUrl":"10.1016/j.pneurobio.2025.102811","url":null,"abstract":"<div><div>The ability to rapidly detect and respond to unexpected auditory stimuli is critical for adaptive behavior, especially during locomotion. Since movement suppresses auditory cortical activity, it remains unclear how salient auditory information influences locomotor circuits. In this work, using in vivo calcium imaging, electrophysiology, chemo- and optogenetics, we investigate the path that relays loud broadband sounds to the dorsal hippocampus (dHPC) and modulates theta oscillations. We demonstrate that noise accelerates theta frequency and decreases its power, effects mediated by entorhinal cortex (EC) and medial septum (MS) inputs while independent of the primary auditory cortex. Activation of dorsal cochlear nucleus (DCN) neurons projecting to the pontine reticular nucleus (PRN) mimics noise-driven hippocampal responses, supporting a brainstem-limbic auditory processing route. Furthermore, noise selectively modulates CA1 pyramidal neuron and interneuron activity, reflecting diverse circuit dynamics. Finally, loud broadband noise stimulus increased theta coherence between the dHPC and the medial prefrontal cortex (mPFC), enhancing interregional synchronization. These results highlight the mechanisms in which the DCN filters behaviorally relevant sounds promoting acoustic motor integration in the hippocampus during locomotion, without direct influence of the auditory cortex.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"252 ","pages":"Article 102811"},"PeriodicalIF":6.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144842491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Eye movements organize excitability state, information coding and network connectivity in the human hippocampus 眼动组织人海马的兴奋状态、信息编码和网络连接。

IF 6.1 2区医学

Progress in Neurobiology Pub Date : 2025-09-01 Epub Date: 2025-08-13 DOI: 10.1016/j.pneurobio.2025.102812

Marcin Leszczynski , Elizabeth Espinal , Elliot Smith , Catherine Schevon , Sameer Sheth , Charles E. Schroeder

{"title":"Eye movements organize excitability state, information coding and network connectivity in the human hippocampus","authors":"Marcin Leszczynski , Elizabeth Espinal , Elliot Smith , Catherine Schevon , Sameer Sheth , Charles E. Schroeder","doi":"10.1016/j.pneurobio.2025.102812","DOIUrl":"10.1016/j.pneurobio.2025.102812","url":null,"abstract":"<div><div>Natural vision is an active sensing process that entails frequent eye movements to sample the environment. Nonetheless vision is often studied using passive viewing with eye position held constant. Using closed-loop eye-tracking, with saccade-contingent stimulation and simultaneous intracranial recordings in surgical epilepsy patients, we tested the critical role of eye movement signals during natural visual processing in the hippocampus and hippocampal-amygdala circuit. Prior work shows that saccades elicit phase reset of ongoing neural excitability fluctuations across a broad array of cortical and subcortical areas. Here we show that saccade-related phase reset systematically modulates neuronal ensemble responses to visual input, enables phase-coding of information across the saccade-fixation cycle and modulates network connectivity between hippocampus and amygdala. The saccade-fixation cycle thus emerges as a fundamental sampling unit, organizing a range of neural operations including input representation, network connectivity and information coding.</div></div><div><h3>Summary</h3><div>Saccade-fixation cycle: a fundamental sampling unit, organizing input representation, information coding and network coordination.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"252 ","pages":"Article 102812"},"PeriodicalIF":6.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Interplay between circadian rhythms and epigenetics in neural stem cells and Alzheimer’s disease 神经干细胞与阿尔茨海默病中昼夜节律和表观遗传学的相互作用。

IF 6.1 2区医学

Progress in Neurobiology Pub Date : 2025-09-01 Epub Date: 2025-08-08 DOI: 10.1016/j.pneurobio.2025.102808

Tânia Cunha Alves , Kamil Musílek , Barbara Monti

{"title":"Interplay between circadian rhythms and epigenetics in neural stem cells and Alzheimer’s disease","authors":"Tânia Cunha Alves , Kamil Musílek , Barbara Monti","doi":"10.1016/j.pneurobio.2025.102808","DOIUrl":"10.1016/j.pneurobio.2025.102808","url":null,"abstract":"<div><div>The circadian clock, as a molecular timekeeper, influences most behavioural and physiological processes. Numerous symptoms associated with neurodegenerative diseases, such as sleep disorders, anxiety, and mood alteration, are linked to circadian clock dysregulation. Dysregulation of the circadian system is increasingly implicated in the onset and progression of Alzheimer's disease, and emerging evidence highlights a bidirectional relationship between Alzheimer’s disease and circadian clock disruption. A crucial point is that the circadian clock regulates adult neurogenesis, a process that is significantly impaired in Alzheimer’s disease. Recent advancements suggest that the dynamic epigenetic mechanisms—including DNA and histone modifications as well as regulation by non-coding RNA—act as a critical regulation for circadian rhythms and neurogenesis. Therefore, research on circadian disruption and, particularly, focus on harmonising the circadian clock with neurogenesis in neurodegenerative diseases may also speed up the creation of innovative, circadian-based treatments to counteract the progress of neurological disorders from a new perspective. In this review, we explore potential epigenetic mechanisms linking the circadian system to neurodegenerative diseases, with a focus on Alzheimer’s Disease.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"252 ","pages":"Article 102808"},"PeriodicalIF":6.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144817411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Npas4 drives the effects of early social isolation on social behaviors and prefrontal parvalbumin neurons Npas4驱动早期社会隔离对社会行为和前额叶小白蛋白神经元的影响。

IF 6.1 2区医学

Progress in Neurobiology Pub Date : 2025-09-01 Epub Date: 2025-08-13 DOI: 10.1016/j.pneurobio.2025.102810

Keshav Jindal , Amanda Ringland , Sydney Fitzcharles , Chase Redd , Damian G. Wheeler , Laurence Coutellier

{"title":"Npas4 drives the effects of early social isolation on social behaviors and prefrontal parvalbumin neurons","authors":"Keshav Jindal , Amanda Ringland , Sydney Fitzcharles , Chase Redd , Damian G. Wheeler , Laurence Coutellier","doi":"10.1016/j.pneurobio.2025.102810","DOIUrl":"10.1016/j.pneurobio.2025.102810","url":null,"abstract":"<div><div>Social behaviors mature during the adolescent period. Prefrontal parvalbumin (PV) neurons have been shown to play a critical role in this process, and their deregulation by early social isolation leads to social deficits in adulthood. However, the molecular mechanisms by which early social isolation affects prefrontal PV neurons causing social impairments remain unclear. Here, we identified the neuronal-specific transcription factor Npas4 as a key player in this process. We first showed that social isolation results in aberrant adolescent developmental trajectories of Npas4 and PV expression in the prefrontal cortex (PFC) leading to prolonged downregulation of Npas4 and upregulation of PV, suggesting an Npas4-driven over-inhibition of prefrontal circuits following early social isolation. Using Npas4 knockout (KO) mice and iDISCO whole brain cFos mapping, we then further implicated Npas4-dependent reduction in prefrontal activity with appearance of sociability deficits in adulthood: Npas4 KO mice failed to show an age-increase in sociability and in activity of the anterior cingulate cortex (ACC) that we observed in wild-type mice during the transition from adolescence to adulthood. Finally, using a viral approach to restore prefrontal Npas4 expression during early adolescence, we were able to rescue the sociability deficits and aberrant expression of PV in the AAC induced by social isolation. Altogether, our findings identified Npas4 as a novel molecular mediator of early social isolation on social deficits, through the role it plays on the adolescent maturation of prefrontal PV neurons.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"252 ","pages":"Article 102810"},"PeriodicalIF":6.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144856204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Corrigendum to “Anatomo-functional organization of insular networks: From sensory integration to behavioral control” [Prog. Neurobiol. 247 (2025) 102748] “岛状神经网络的解剖功能组织：从感觉整合到行为控制”的勘误表。中国生物医学工程学报，2016(5):357 - 357。

IF 6.1 2区医学

Progress in Neurobiology Pub Date : 2025-08-01 Epub Date: 2025-06-15 DOI: 10.1016/j.pneurobio.2025.102795

Luciano Simone , Fausto Caruana , Elena Borra , Simone Del Sorbo , Ahmad Jezzini , Stefano Rozzi , Giuseppe Luppino , Marzio Gerbella

引用次数: 0

Differential susceptibility to repeated social stress induces synaptic plasticity impairment and cognitive deficit in the 5xFAD mouse model 在5xFAD小鼠模型中，对重复社会应激的不同易感性导致突触可塑性损伤和认知缺陷。

IF 6.7 2区医学

Progress in Neurobiology Pub Date : 2025-08-01 Epub Date: 2025-06-19 DOI: 10.1016/j.pneurobio.2025.102797

Eun-Jeong Yang , Md Al Rahim , Sibilla Masieri , Giulio Maria Pasinetti

{"title":"Differential susceptibility to repeated social stress induces synaptic plasticity impairment and cognitive deficit in the 5xFAD mouse model","authors":"Eun-Jeong Yang , Md Al Rahim , Sibilla Masieri , Giulio Maria Pasinetti","doi":"10.1016/j.pneurobio.2025.102797","DOIUrl":"10.1016/j.pneurobio.2025.102797","url":null,"abstract":"<div><div>Stress-related disorders including depression are common comorbidities in Alzheimer's Disease (AD). In AD, heightened stress reactivity may contribute to an increased risk of cognitive dysfunction. This study aimed to investigate the differential responses of wild-type (WT) and 5xFAD mice, a model of AD, to repeated social defeat stress (RSDS) and explore the molecular mechanisms associated with stress susceptibility. Both WT and 5xFAD mice exhibited susceptibility to initial exposure to RSDS, with a greater proportion of stress-susceptible (Sus) individuals observed in 5xFAD mice compared to WT mice. In presymptomatic 5xFAD mice repeatedly exposed to RSDS, cognitive impairment was evident through a lower discrimination index in the NOR test compared to controls. To investigate the effects of RSDS on peripheral immune responses, we performed CyTOF analysis, revealing a significant increase in CD8 + and CD4 + memory T cells exclusively in the peripheral blood of 5xFAD-Sus mice. To further explore the molecular mechanisms underlying RSDS in the brain, RNA sequencing revealed distinct patterns of differentially expressed genes associated with inflammatory pathways in stress-Sus mice. Specifically, 5xFAD-Sus mice exhibited dysregulation in immune-related pathways, while WT-Sus mice displayed alterations in pathways related to cell adhesion and cytoskeletal organization. In addition, when comparing 5xFAD-Sus to 5xFAD-resilience mice, significant disruptions in synaptic plasticity pathways were observed in 5xFAD-Sus mice, and these changes were accompanied by cognitive impairment. These findings suggest that increased stress susceptibility in 5xFAD is linked to distinct peripheral immune dysregulation, potentially contributing to synaptic plasticity impairments and cognitive dysfunction in the early stages of AD.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"251 ","pages":"Article 102797"},"PeriodicalIF":6.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0