Experimental Neurology最新文献

{"title":"Activation of oligodendrocyte precursor cells triggers cognitive dysfunction and synaptic defects in SAE","authors":"You Wu ,&nbsp;Zhengdong Yang ,&nbsp;Huiqing Liu ,&nbsp;Jin Li ,&nbsp;Renhuai Liu ,&nbsp;Yi Li ,&nbsp;Yu Chen ,&nbsp;Binxiao Su","doi":"10.1016/j.expneurol.2026.115670","DOIUrl":"10.1016/j.expneurol.2026.115670","url":null,"abstract":"<div><div>Sepsis-associated encephalopathy (SAE) is defined as a diffuse neurological dysfunction that occurs secondary to sepsis, in the absence of direct central nervous system infection, and is associated with high rates of incidence, mortality, and disability. Despite its clinical significance, the neuropathological mechanisms underlying SAE are not yet fully understood, making its pathogenesis a focal point of ongoing research. Oligodendrocyte precursor cells (OPCs), which are the most proliferative cell type within the central nervous system, primarily contribute to the generation of mature oligodendrocytes and are integral to myelination and the maintenance of myelin. Nevertheless, the role and pathological changes of OPCs during the acute phase of SAE remain inadequately characterized. This study illustrates that OPCs in the hippocampal CA1 region may undergo immune activation under SAE conditions, characterized by significantly elevated inflammatory transcription and phagocytic capacity. Additionally, activated OPCs in SAE mice may contribute to the synaptic pruning of neurons. By generating PDGFRa-Cre/ERT transgenic mice and conducting stereotactic injections of pAAV-EGFP-flex-DTA virus into the hippocampal CA1 region to selectively ablate OPCs, we observed a significant enhancement in cognitive function in SAE mice. This improvement is likely due to the alleviation of synaptic structural and functional impairments in neurons. Our findings indicate that OPCs play a critical role in the pathogenesis of SAE, highlighting their potential as a novel therapeutic target for this condition.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"399 ","pages":"Article 115670"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146075847","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}

{"title":"Low-frequency TMS ameliorates neonatal hypoxia-ischemia injury by normalizing glutamatergic transmission in penumbra","authors":"Ivan Goussakov,&nbsp;Sylvia Synowiec,&nbsp;Alexander Drobyshevsky","doi":"10.1016/j.expneurol.2026.115669","DOIUrl":"10.1016/j.expneurol.2026.115669","url":null,"abstract":"<div><div>Perinatal hypoxic-ischemic encephalopathy (HIE) is a leading cause of morbidity and mortality in term neonates. The current standard of care, therapeutic hypothermia, provides only partial neuroprotection. This study investigates the potential of low-frequency transcranial magnetic stimulation (LF-TMS) as a novel non-pharmacological adjunct therapy by targeting a key pathological mechanism of HIE: a persistent, pathological increase in glutamatergic synaptic transmission, or hypoxic long-term potentiation.</div><div>Using a neonatal mouse model of hypoxia-ischemia, we administered a single session of LF-TMS 30 min after the hypoxic event. We then evaluated its effects on synaptic function via slice electrophysiology and on brain injury volume using serial MRI. Our results show that hypoxia-ischemia induced significant and lasting synaptic potentiation in the perilesional region of the somatosensory cortex. LF-TMS treatment successfully reduced this elevated glutamatergic response to control levels, suggesting a therapeutic mechanism similar to long-term depression and/or depotentiation by downregulating AMPA receptors.</div><div>LF-TMS provided significant neuroprotection, as demonstrated by reductions in volumes of the ischemic core and penumbra 48 h after the injury. LF-TMS did not alter excitability in sham-treated mice, confirming its safety as a targeted intervention for pathological conditions without affecting normal brain function. This study supports that LF-TMS is a promising neuroprotective strategy that mitigates brain injury in a neonatal hypoxia-ischemia model.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"399 ","pages":"Article 115669"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146061048","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}

{"title":"Neuropathic pain after spinal cord injury: Mechanisms, animal models and pain assessments","authors":"Zean Tao ,&nbsp;Xiaoling Zhou ,&nbsp;Lixia Jin ,&nbsp;Nixi Xu ,&nbsp;Yuanwu Cao ,&nbsp;Zhaoyi Wu ,&nbsp;Chang Jiang ,&nbsp;Zixian Chen","doi":"10.1016/j.expneurol.2026.115678","DOIUrl":"10.1016/j.expneurol.2026.115678","url":null,"abstract":"<div><div>Neuropathic pain after spinal cord injury (SCI-NP) often has lifelong and significant negative effects. Therefore, understanding its underlying mechanisms is a current research priority.</div><div>SCI-NP involves central sensitization, neuroinflammation and functional remodeling in the brain, hyperexcitability of primary sensory neurons, and peripheral–central interactions. The mechanism of SCI-NP at the spinal cord level is an important one to study. Glial cell activation and proinflammatory pathways in the spinal cord are the key drivers that lead to central sensitization at the spinal cord level, and they constitute the main mechanisms of current research. However, the mechanism of SCI-NP remains unclear, mainly because of the lack of standardized and uniform animal models in preclinical studies.</div><div>Animal models provide a basis for the mechanistic study of SCI-NP, but the stability and repeatability of these models pose problems. Behavioral evaluation of animal models of SCI-NP has focused on mechanical and heat-induced pain thresholds, but this phenotype is different from the clinical diagnostic criteria of SCI-NP in patients, which includes at least four positive signs according to the DN4 scale. Electrophysiological recordings, especially from spinal dorsal horn neurons and dorsal root ganglia neurons, provide important support for <span>SCI</span>-NP research.</div><div>In summary, the development of SCI-NP involves a complex pathological process, and its mechanisms remain incompletely understood. Existing models and detection methods require refinement. This review focuses on the research progress in this field and looks forward to future research directions.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"399 ","pages":"Article 115678"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131738","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}

{"title":"Ectopically overexpressed glycine transporter 2 contributes to epileptogenesis in DEPDC5-related epilepsy","authors":"Tao Yang ,&nbsp;Rajat Banerjee ,&nbsp;Mirte Scheper ,&nbsp;Mi Jiang ,&nbsp;Steven Dai ,&nbsp;Eleonora Aronica ,&nbsp;Yu Wang","doi":"10.1016/j.expneurol.2026.115668","DOIUrl":"10.1016/j.expneurol.2026.115668","url":null,"abstract":"<div><div>Loss-of-function mutations in DEPDC5 (DEP domain-containing protein 5), a critical negative regulator of mTORC1 (mechanistic Target of Rapamycin Complex 1), are often identified in patients with refractory epilepsy. To understand its underlying pathogenesis and develop novel therapeutics, we used a highly clinically relevant rat model of DEPDC5-related epilepsy and resected human patient tissues to profile the molecular architecture in the dysplastic cortex. We report here that <em>Slc6a5</em> (solute carrier family 6 member 5 gene), a marker gene for glycinergic inhibitory neurons, is ectopically overexpressed in mutant excitatory neurons in both experimental animal and human tissues. Using CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) in utero electroporation (IUE) to simultaneously knock out <em>Depdc5</em> and <em>Slc6a5</em> in forebrain excitatory neurons reduces seizure frequency and duration. These data suggest that <em>SLC6A5</em> plays an important role in the epileptogenesis of DEPDC5-related epilepsy, although the underlying mechanisms remain unclear.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"399 ","pages":"Article 115668"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146050958","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}

{"title":"β-1, 3-galactosyltransferase 2 promotes cerebral angiogenesis and neurological recovery during the ischemic repair phase through glycosylation modification of TGF-βR(II)/ALK1","authors":"Chang Liu ,&nbsp;Yao Ma ,&nbsp;Jiachen Li ,&nbsp;Yunhao Xu ,&nbsp;Meixuan Li ,&nbsp;Hong Li ,&nbsp;Zongze Li ,&nbsp;Zhanyou Wang ,&nbsp;Jia Liang ,&nbsp;Peng Wang","doi":"10.1016/j.expneurol.2026.115651","DOIUrl":"10.1016/j.expneurol.2026.115651","url":null,"abstract":"<div><div>β-1,3-galactosyltransferase 2 (B3galt2) has been increasingly recognized as an essential mediator in the pathogenesis of ischemic stroke (IS); nonetheless, its exact functional role has not been fully elucidated. This research aimed to clarify the regulatory mechanisms by which B3galt2 influences cerebral angiogenesis during the repair phase following ischemic injury. A mouse model of cerebral ischemia/reperfusion (I/R) injury was generated by subjecting animals to 1-h middle cerebral artery occlusion (MCAO), succeeded by reperfusion for varying time intervals. Recombinant human B3galt2 (rh-B3galt2) was administered intranasally beginning on day one post-injury and continued until tissue collection. Experimental outcomes revealed that rh-B3galt2 substantially diminished brain atrophy and enhanced neurological recovery during the repair phase of ischemia. Furthermore, rh-B3galt2 facilitated angiogenesis through increased expression of vascular endothelial growth factor A (VEGFA) and the tight junction proteins, occludin and claudin 5. Moreover, rh-B3galt2 activated the TGF-βR(II)/ALK1/Smad1/5 pathway. The galactosylation levels of TGF-βR(II) and ALK1 were increased after rh-B3galt2 treatment, suggesting that B3galt2 may regulate TGF-βR(II) and ALK1 through glycosylation modification. Moreover, the advantageous impacts of rh-B3galt2 on reducing brain atrophy and alleviating neurological deficits were reversed upon treatment with the ALK1 inhibitor, ML347. ML347 also counteracted the angiogenic promotion induced by rh-B3galt2, demonstrating that inhibition of ALK1 abolishes the protective benefits mediated by rh-B3galt2. Collectively, the results indicated that rh-B3galt2 significantly promotes angiogenesis and neurological function recovery during the cerebral ischemic repair stage, likely by regulating TGF-βR(II)/ALK1/Smad1/5 signaling pathway through glycosylation modification.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"399 ","pages":"Article 115651"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146006504","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}

{"title":"DLK inhibition has sex-specific effects on neuroprotection and locomotor recovery after spinal cord injury","authors":"John C. Aldrich ,&nbsp;Samantha M. Alman ,&nbsp;Sydney E. Lee ,&nbsp;Ashley R. Scheinfeld ,&nbsp;Chelsea C. Zhang ,&nbsp;Averi L. Pike ,&nbsp;Fiona C. Bremner ,&nbsp;Olivia Calderon ,&nbsp;Sunil Goodwani ,&nbsp;William J. Ray ,&nbsp;Andrew D. Gaudet","doi":"10.1016/j.expneurol.2026.115681","DOIUrl":"10.1016/j.expneurol.2026.115681","url":null,"abstract":"<div><div>Spinal cord injury (SCI) causes devastating functional deficits, in part due to neuroinflammation, oxidative stress, and excitotoxicity that drive death of lesion-adjacent viable neurons. Dual leucine zipper kinase (DLK) is a neuron-enriched kinase that responds to cellular stress by activating the c-Jun N-terminal kinase (JNK) pathway, driving both stress-responsive gene expression and neuronal apoptosis. We hypothesized that SCI would robustly activate DLK signaling and that acute pharmacological inhibition of DLK would suppress JNK pathway activation, thereby enhancing neuroprotection and locomotor recovery in our mouse model of moderate contusion SCI. Using western blotting, we observed that SCI induced strong and sustained activation of the JNK pathway in the injured spinal cord starting at 4 h post-injury through 7 days. Complementary analysis of single-nucleus RNA-seq revealed that DLK expression is highly enriched in neurons across all injury phases. Following SCI, neurons exhibited robust, time-dependent upregulation of multiple DLK-responsive transcripts, consistent with sustained pathway activation during the acute and subacute periods. Systemic treatment with the selective DLK inhibitor IACS-52825 effectively suppressed intraspinal JUN activation in a dose-dependent manner. However, unexpectedly, treatment delayed functional recovery and expanded lesion volume by 71% in male mice with no significant effect in females. These findings highlight the complex roles of DLK signaling after SCI, revealing a need to understand the sex-specific molecular mechanisms that modulate injury outcomes. Future studies should further optimize timing, location, and cellular targeting of DLK therapeutic strategies to improve neuroprotection and neurologic recovery after SCI.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"399 ","pages":"Article 115681"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146156546","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}

{"title":"Exosomes-mediated delivery of miR-27a-3p antagomir alleviates white matter injury by regulating PPARγ/PRDX1/JNK pathway after subarachnoid hemorrhage in rats","authors":"Zhaosi Zhang ,&nbsp;Fuming Liang ,&nbsp;Daochen Wen ,&nbsp;Hong Chen ,&nbsp;Nina Gu ,&nbsp;Zhao Li ,&nbsp;Lin Wang ,&nbsp;Yingwen Wang ,&nbsp;Qiuling Pan ,&nbsp;Yajun Zhu ,&nbsp;Dan Xu ,&nbsp;Xiaochuan Sun ,&nbsp;Chongjie Cheng ,&nbsp;Jin Yan","doi":"10.1016/j.expneurol.2026.115667","DOIUrl":"10.1016/j.expneurol.2026.115667","url":null,"abstract":"<div><div>White matter injury (WMI) is a critical factor contributing to poor neurological outcomes following subarachnoid hemorrhage (SAH). MicroRNAs (miRNAs) are key regulators of WMI-related pathology and can be delivered via exosomes, yet their mechanisms and therapeutic potential remain largely unexplored. In this study, miRNA sequencing revealed a significant upregulation of miR-27a-3p in peripheral blood exosomes after SAH, which was further confirmed in white matter tissue. BV2 cell–derived exosomes loaded with miR-27a-3p antagomir were administered intranasally and effectively targeted oligodendrocytes. Treatment with these exosomes alleviated WMI by reducing oligodendrocyte apoptosis and promoting the proliferation and differentiation of oligodendrocyte precursor cells, leading to improved neurological and electrophysiological recovery. Mechanistically, miR-27a-3p inhibited PPARγ, resulting in downregulation of PRDX1 and activation of the JNK pathway, which triggered oligodendrocyte apoptosis. These findings demonstrate that exosome-mediated delivery of miR-27a-3p antagomir mitigates SAH-induced WMI through modulation of the PPARγ/PRDX1/JNK axis, providing a promising noninvasive therapeutic approach for enhancing white matter repair and functional recovery after SAH.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"399 ","pages":"Article 115667"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146046363","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}

{"title":"B7-H3 upregulation in ischemic stroke: friend or foe?","authors":"Siva Reddy Challa ,&nbsp;Isidra M. Baker ,&nbsp;Casimir A. Fornal ,&nbsp;Sahil Reddy Mada ,&nbsp;Nabeeha Khan ,&nbsp;Samantha N. Jackson ,&nbsp;Erick Saldes ,&nbsp;Jeffrey D. Klopfenstein ,&nbsp;Swapna Asuthkar ,&nbsp;Krishna Kumar Veeravalli","doi":"10.1016/j.expneurol.2026.115675","DOIUrl":"10.1016/j.expneurol.2026.115675","url":null,"abstract":"<div><div>B7-H3 (CD276) is an immune checkpoint co-signaling molecule expressed on immune and non-immune cells. It is best known for suppressing T-cell responses but can also promote inflammation depending on the microenvironment. In neuroinflammatory models such as experimental autoimmune encephalomyelitis, B7-H3 expression increases concomitantly with the inflammatory response, and its inhibition is associated with reduced disease progression. Although its role in ischemic stroke remains unclear, we hypothesized that cerebral ischemia/reperfusion (I/R) would upregulate B7-H3 expression in the ischemic brain and that increased B7-H3 expression would positively correlate with pro-inflammatory cytokine expression. Young and aged male and female rodents, including normotensive and spontaneously hypertensive rats to model comorbid hypertension, underwent transient middle cerebral artery occlusion (MCAO) followed by reperfusion. Brain tissue was collected on post-MCAO days 1, 3, 5, or 7. B7-H3 mRNA was analyzed by real-time PCR, whereas protein expression was assessed by Western blotting and immunohistochemistry at selected time points. B7-H3 expression was significantly upregulated in the ischemic brain across sexes, age groups, and species. The extent of B7-H3 degradation was influenced by species, sex, age, and time after cerebral I/R. Upregulation of B7-H3 was observed at both the mRNA and protein levels and was localized primarily to the somatosensory cortex and caudate putamen in the ipsilateral (ischemic) hemisphere, the main regions affected in this MCAO model. Elevated B7-H3 expression in the ischemic brain positively correlated with the pro-inflammatory mediator TNFα. In rats, the temporal profile of B7-H3 expression paralleled the early inflammatory phase associated with secondary tissue damage after ischemic stroke. These findings identify B7-H3 as an ischemia-induced immune checkpoint molecule in the brain that may modulate post-stroke immune responses and support further investigation into its beneficial versus detrimental roles in neuroinflammation and its potential as a therapeutic target following cerebral I/R.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"399 ","pages":"Article 115675"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146097044","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}

{"title":"Unveiling distinct neuroimmune responses in mouse models of cervical spinal cord injury: Hemisection versus hemicontusion","authors":"Wei Chen ,&nbsp;Lucille Adam ,&nbsp;Michel-Flutot Pauline ,&nbsp;Arnaud Mansart ,&nbsp;Stéphane Vinit ,&nbsp;Isabelle Vivodtzev","doi":"10.1016/j.expneurol.2026.115661","DOIUrl":"10.1016/j.expneurol.2026.115661","url":null,"abstract":"<div><div>Traumatic cervical spinal cord injury (cSCI) causes severe neurological deficits and long-term disability. Preclinical models such as cervical vertebrate level 2 (C2) hemisection (C2HS), which disrupts communication between respiratory centers and the phrenic motoneurons pool, have been used for decades to study respiratory dysfunction and neuroinflammation after cSCI. Recently, contusive injuries such as cervical vertebrate level 3 hemicontusion (C3HC) have been increasingly employed, as they induce phrenic motoneuron damage and offer a more clinically relevant model of SCI. However, these two different models may engage distinct pathophysiological cascades, raising concerns about the generalizability of findings across injury paradigms. In this study, we compared neuroimmune responses following C2HS or C3HC in mice. Animals underwent either lesion, and spinal cord segments (C1-C8) were collected seven days post-injury for immuno-histological analyses around the lesion level and flow cytometry analyses at the lesion level. We observed that C2HS preserved more neurons accompanied by an upregulation of CD86 and F4/80 in macroglia, markers of activated macrophages, suggesting a response oriented toward phagocytic and reparative functions. This phenotype was associated with limited pro-inflammatory cell infiltration and normalized level of systemic IL-6 level. Conversely, C3HC induced more extensive tissue damage, heightened microglial activation, a trend toward increased astrocytic reactivity, and significantly elevated CSPG levels on the contralateral side. Moreover, a persistent NK cell, neutrophil, and CD43⁺ infiltrating cells, along with sustained elevation of circulating IL-6 These findings demonstrate distinct neuroinflammatory signatures and repairing mechanisms between models. This study underscores, for the first time, how injury type shapes neuroimmune mechanisms, reinforcing the need for lesion-specific therapeutic strategies in cervical spinal cord injury.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"399 ","pages":"Article 115661"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146040591","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}

{"title":"Long-term dietary interventions fail to mitigate functional connectivity loss and cognitive decline in the TgF344-AD rat model of Alzheimer's disease","authors":"Judith R.A. van Rooij ,&nbsp;Monica van den Berg ,&nbsp;Manoy Van Vosselen ,&nbsp;Elke Calus ,&nbsp;Tamara Vasilkovska ,&nbsp;Lauren Kosten ,&nbsp;Ignace Van Spilbeeck ,&nbsp;Johan Van Audekerke ,&nbsp;Debby Van Dam ,&nbsp;Daniele Bertoglio ,&nbsp;Mohit H. Adhikari ,&nbsp;Marleen Verhoye","doi":"10.1016/j.expneurol.2026.115647","DOIUrl":"10.1016/j.expneurol.2026.115647","url":null,"abstract":"<div><div>Short-term caloric restriction (CR) and resveratrol (Rsv) supplementation have shown potential in preserving brain function in aging and neurodegenerative diseases such as AD. However, there is a lack of knowledge regarding the potential benefits of long-term CR or Rsv on brain health in context of AD. Therefore, we aimed to assess the effects of short-term (1 month) CR and Rsv administration on resting-state functional connectivity (rs-FC), as well as the effect of long-term (8 months) CR or Rsv supplementation on rs-FC, spatial memory, amyloid burden, and neuroinflammation in male and female TgF344-AD (Tg) and wild-type (WT) rats. In Tg rats, short-term CR decreased rs-FC in female rats, while long-term CR decreased rs-FC and modestly improved spatial memory in male rats. Long-term CR and Rsv altered regional amyloid burden, and CR decreased IBA-1 in males without affecting GFAP. Overall, long-term CR and Rsv failed to mitigate FC loss and cognition, underscoring the potentially limited impact of these dietary interventions in AD.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"398 ","pages":"Article 115647"},"PeriodicalIF":4.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145973428","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}