Neurochemical Research最新文献

{"title":"Pharmacological Evaluation and In-Silico Study of Sabinene as a Potential Anti-Alzheimer’s Drug in AlCl3-Induced Rat Model via BACE-1 and GSK3β Modulation","authors":"Pankti Parmar,&nbsp;Heena Chauhan,&nbsp;Palmi Modi,&nbsp;Dipa Israni","doi":"10.1007/s11064-025-04523-7","DOIUrl":"10.1007/s11064-025-04523-7","url":null,"abstract":"<div><p>Alzheimer’s disease (AD) is a progressive and debilitating neurodegenerative disorder. β-site amyloid precursor protein cleaving enzyme 1 (BACE1) and glycogen synthase kinase-3β (GSK3β) contribute to Aβ plaque development, tau hyperphosphorylation, neurofibrillary tangles, and neuronal dysfunction in AD pathogenesis. This study aimed to investigate the neuroprotective potential of sabinene in an Aluminum chloride (AlCl₃)-induced model of AD in male Wistar rats. Thirty male Wistar rats were randomly divided into six groups (<i>n</i> = 6 per group). Group I (control) received normal saline for 30 days. Groups II–V were administered only AlCl₃ (100 mg/kg, orally) for 20 consecutive days to induce AD-like pathology, which was confirmed through behavioral assessments. Following induction, Group II (AD control) received 1% Tween 80; Group III (standard treatment) was administered rivastigmine (2.5 mg/kg); while Groups IV–VI received sabinene at doses of 5, 10, and 20 mg/kg, respectively, for 10 days 1 h prior to AlCl₃. Behavioral evaluations were conducted on days 0, 20, and 31. On the 31st day, animals were sacrificed for biochemical and molecular analyses. In silico molecular docking studies revealed that sabinene exhibited a higher binding affinity towards AD-related targets (BACE1, GSK-3β, TACE, and AChE) compared to rivastigmine. In vivo, sabinene treatment significantly mitigated oxidative stress, restored antioxidant enzyme activities, reduced pro-inflammatory cytokine levels, AChE, BACE1, and GSK3β expression, and ameliorated histopathological alterations in the rat brain. Thus, sabinene exerts potent neuroprotective and disease-modifying effects in AlCl₃-induced AD via AchE, BACE-1, and GSK3β Modulation.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144894002","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}

{"title":"Coapplication of Adenine with Inosine or Guanosine Supports Rapid ATP Restoration by ATP-deprived Cultured Primary Astrocytes","authors":"Gabriele Karger,&nbsp;Ralf Dringen","doi":"10.1007/s11064-025-04511-x","DOIUrl":"10.1007/s11064-025-04511-x","url":null,"abstract":"<div><p>Astrocytes contain a high concentration of adenosine triphosphate (ATP) that enables these cells to perform their physiological functions in brain. To investigate the mechanisms involved in astrocytic ATP restoration, the ATP content of cultured primary rat astrocytes was first depleted by a preincubation with the mitochondrial uncoupler BAM15 before extracellular substrates and their combinations were applied to foster ATP restoration. To test for the contribution of the purine salvage pathway to synthesize new adenosine monophosphate (AMP) for ATP restoration, several purine nucleosides and purine bases as well as their combinations were applied. In the absence of glucose, partial ATP restoration was found for incubations with inosine and guanosine that was lowered by forodesine, an inhibitor of purine nucleoside phosphorylase. In glucose-fed cells, the coapplication of micromolar concentrations of adenine with inosine or guanosine, but not with ribose, accelerated ATP restoration in a concentration-dependent manner. By such treatments, 80% of the initial ATP content were restored within 40 min. The supporting effects of inosine and guanosine on ATP restoration were prevented by the presence of forodesine, demonstrating the contribution of purine nucleoside phosphorylase in the ATP restoration observed. These data demonstrate that ATP-deprived astrocytes need for rapid ATP restoration - in addition to glucose as energy substrate - an adenine source and inosine or guanosine as precursor for the ribose phosphate moiety of ATP.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11064-025-04511-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144892447","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}

{"title":"Recent Insights on Supraspinal Astrocytes in Chronic Pain","authors":"Alessandro Di Spiezio,&nbsp;Marta Gómez-Gonzalo,&nbsp;Angela Chiavegato,&nbsp;Micaela Zonta","doi":"10.1007/s11064-025-04503-x","DOIUrl":"10.1007/s11064-025-04503-x","url":null,"abstract":"<div><p>Chronic pain is a debilitating, life-altering condition that affects a significant portion of the global population, impacting approximately one fifth of people in Europe and one third of people worldwide. Clinical and experimental efforts are increasingly converging to deepen our comprehension of the molecular, cellular and circuit-level mechanisms underlying persistent pain. While most studies have traditionally focused on alterations of nociceptive pathways in neurons, growing evidence highlights the critical role of astrocytes in modulating these pathways and contributing to the development of the central sensitization that characterizes chronic pain. Moreover, astrocytes are also implicated in pain-associated maladaptive behaviours and cognitive impairments. In this context, we review the latest findings on astrocyte involvement in chronic pain and its related mood and cognitive comorbidities.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div><div><p>Created in BioRender. Chiavegato, A. (2025). https://BioRender.com/42hblyi</p></div></div></figure></div></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11064-025-04503-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144892448","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}

{"title":"Synbiotics as Modulators of Developing Brain for Reproductive Development Via Estrogen Receptors in Male Coturnix Coturnix Japonica","authors":"Aamir Khan,&nbsp;Malabika Sikdar,&nbsp;Naveen Kango,&nbsp;Rashmi Srivastava","doi":"10.1007/s11064-025-04528-2","DOIUrl":"10.1007/s11064-025-04528-2","url":null,"abstract":"<div><p>The brain-gut–microbiome axis represents a bidirectional communication linking the gastrointestinal microbiome with immunity, digestion, reproduction and nervous system. Dietary supplementation of <i>Lactobacillus rhamnosus</i>, <i>Bifidobacterium longum</i> and mannan-oligosaccharides may modulate the brain-gut-axis and also have an effect on male reproductive physiology. Therefore, the study aims to explore the reproductive and neuronal physiology potentials of synbiotics in immature male Japanese quails. To achieve this, two weeks old quails were supplemented with 1% <i>Lactobacillus rhamnosus</i> (L), <i>Bifidobacterium longum</i> (B) and mannan-oligosaccharides (M) in their diet, individually as well as in combinations (LB and LBM) for 28days. The oxidative stress markers including malondialdehyde (MDA), hydrogen peroxide (H₂O₂), advanced oxygen protein products (AOPPs); antioxidant enzymes {Superoxide Dismutase (SOD), Catalase} and coenzyme Glutathione (GSH); monoamine oxidase (MAO) and acetylcholinesterase (AchE) activity were estimated in the brain. Inflammatory biomarkers (IL-10, IL-1β and NF-κB), apoptotic biomarkers (caspase-3 and caspase-7) and for reproductive aspect viz. gonadotropin releasing hormone (GnRH) and estrogen receptors (ER-α and ER-β) were analyzed by immunofluorescence in the brain. The results revealed that dietary supplementation with 1% LBM or synbiotics significantly enhances the number of neurons in the hippocampal area, antioxidant enzymes (SOD and Catalase) while it reduces MDA, H₂O₂ and AOPP. Synbiotics increases IL-10 expression and a substantial reduction in IL-1β and NF-κB which limits inflammation as well as apoptosis (Caspase-3 &amp; Caspase-7) with increased AchE, MAO activity in the developing brain. Our findings indicate that synbiotics interfere and enhance neuronal development processes and are associated with fertility manifested by upregulated expression of GnRH, ER-α, ER-β in brain. Overall, combined use of pro, pre, synbiotics have a synergistic effect and serve as modulators in neuro-immune processes and fertility in developing brain of quail.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144880809","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}

{"title":"Role of Glial Trace Amine Associated Receptor 1 (TAAR1) and Microbiota in Schizophrenia","authors":"Vassiliy Tsytsarev,&nbsp;Anastasia N. Vaganova,&nbsp;Anna Volnova,&nbsp;Zoia Fesenko,&nbsp;Bruk Getachew,&nbsp;Raul R. Gainetdinov,&nbsp;Yousef Tizabi","doi":"10.1007/s11064-025-04525-5","DOIUrl":"10.1007/s11064-025-04525-5","url":null,"abstract":"<div><p>Trace amine-associated receptors (TAARs) are a class of G protein-coupled receptors that respond to metabolic derivatives of the amino acids such as phenylalanine, tyrosine, and tryptophan. Trace amines derive their name from the fact that their concentration in the periphery as well as in the central nervous system (CNS) is in trace amounts compared to the parent compound or other monoamine neurotransmitters such as dopamine, norepinephrine, or serotonin. Genetic, pharmacological and neurobiological studies have linked TAAR1, the most studied receptor of the TAARs to the pathophysiology of schizophrenia (SCZ), the current treatments of which are limited. Recent developments in the field implicate glial-microbiota interactions in SCZ pathophysiology. TAAR1 interactions with the glial cells and the gut microbiota (GM) makes it a suitable candidate as a novel target in SCZ. In this review, following brief descriptions of the known neurobiological substrates of SCZ, we delve into the specific roles of glial cells, including analysis of the public transcriptomic data, their interaction with GM and the potential integrator role of TAAR1 in glial-GM signaling relevant to SCZ. Finally, we suggest how TAAR1 manipulation may be exploited in this devastating neuropsychiatric disorder.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144880805","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}

{"title":"Diminazene Alleviates Neuroinflammation in Ischemic Stroke by Inhibiting Astrocytic Endoplasmic Reticulum Stress and Oxidative Stress","authors":"Caidong Liu,&nbsp;Qiang Peng,&nbsp;Shiyao Wang,&nbsp;Zhaohan Xu,&nbsp;Ye Hong,&nbsp;Lin Zhu,&nbsp;Mengmeng Gu,&nbsp;Jinfeng Lyu,&nbsp;Yingdong Zhang,&nbsp;Rui Duan","doi":"10.1007/s11064-025-04530-8","DOIUrl":"10.1007/s11064-025-04530-8","url":null,"abstract":"<div><p>Acute ischemic stroke (AIS) is a common medical emergency worldwide, and reducing cerebral ischemia/reperfusion injury (CI/RI) is a crucial strategy for AIS treatment. Diminazene aceturate (DIZE) has demonstrated therapeutic potential in alleviating neurodegenerative diseases, but its specific functions in AIS remain a puzzle. This research aims to investigate the role and mechanisms of DIZE in CI/RI. C57BL/6J mice were treated with DIZE via intracerebroventricular injection for a week and middle cerebral artery occlusion/reperfusion (MCAO/R) models were established. Neurobehavioral tests, TTC staining and HE staining were adapted to detect neuroprotective effect of DIZE on MCAO/R mice. Primary cultures of astrocytes were prepared and exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) to simulate in vitro ischemia/reperfusion. The IL-1β, IL-6 and TNF-α levels were detected by qRT-PCR and ELISA. Oxidative stress and lipid peroxidation indicators were measured using commercial assay kits. Western blot and immunofluorescence staining were used to measure the related protein levels. We found that DIZE alleviated neuronal injury and suppressed both neuroinflammation and astrocyte reactive changes in MCAO/R mice. In vitro, DIZE inhibited the release of inflammatory factors in primary cultures of astrocytes subjected to OGD/R. Furthermore, DIZE inhibited endoplasmic reticulum stress-mediated IRE1α-NF-κB pathway, increased NRF2 levels and suppressed oxidative stress, which was consistently observed in vivo and in vitro. Our study indicated that DIZE exerts a protective effect on CI/RI, and this effect may be achieved by DIZE inhibiting endoplasmic reticulum stress and oxidative stress in astrocytes, thereby suppressing astrocyte-mediated neuroinflammation.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144880807","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}

{"title":"Elucidating the Neuroprotective Mechanism of 5,7-Dimethoxyflavone and 5,7’,4’-Trimethoxyflavone Through In Silico Target Prediction and in Memory-Impaired Mice","authors":"Nur Intan Saidaah Mohamed Yusof,&nbsp;Kalavathy Ramasamy,&nbsp;Fazlin Mohd Fauzi","doi":"10.1007/s11064-025-04524-6","DOIUrl":"10.1007/s11064-025-04524-6","url":null,"abstract":"<div><p>5,7-dimethoxyflavone (DMF) and 5,7,4’-trimethoxyflavone (TMF) are natural methoxyflavones known for their potential neuroprotective properties. This study investigates their mechanisms of action through in silico target predictions and memory-impaired mice. Ligand-based and proteochemometric models were used to predict potential protein targets, followed by molecular docking using PyRx and Discovery Video Visualiser. To validate these findings, DMF and TMF (10/20/40 mg/kg) were administered to LPS-induced mice for 21 days. Morris Water Maze (MWM) and Open Field Test (OFT) were conducted to assess cognitive functions. Expression levels of predicted targets were determined by RT-PCR, and enzyme-linked immunosorbent assay was conducted to measure BDNF, Aβ, and pro-inflammatory markers. GABRA1, GABRG2, 5-HT_2A, IGF1R, and 5-HT_2C were predicted for DMF. Meanwhile, GABRG2, 5-HT_2A, 5-HT_2B, and 5-HT_2C were predicted for TMF. Molecular docking showed DMF formed strong binding interactions with GABRA1 and GABRG2 (9.40 kcal/mol), interacting with His102 and Tyr160. Meanwhile, TMF formed strong binding interactions with 5-HT_2A (− 9.30 kcal/mol) interacting with Ser242 and Ser159. TMF enhanced spatial memory in MWM, while both compounds reduced anxiety-related measures in OFT. DMF significantly upregulated hippocampal mRNA of GABRA1, 5-HT_2A, and 5-HT_2C, while TMF increased GABRG2, 5-HT_2B, and 5-HT_2C expression. Additionally, both compounds significantly reduced Aβ, IL-1β, IL-6, and TNF-α levels, while DMF-treated groups significantly increased BDNF level. These findings suggest that DMF and TMF exert neuroprotective effects when administered prophylactically, acting through distinct molecular targets involved in neurotransmission and inflammation. Their multi-target activity makes them promising candidates for early intervention in Alzheimer’s disease.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11064-025-04524-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144880804","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}

{"title":"Salidroside Attenuates Epilepsy and Cognitive Dysfunction in Rats by Downregulating Complement C3-C3aR Pathway-Mediated Activation of Microglia and Astrocytes","authors":"Manqian Huang,&nbsp;Meiling Tang,&nbsp;Lu Liu","doi":"10.1007/s11064-025-04514-8","DOIUrl":"10.1007/s11064-025-04514-8","url":null,"abstract":"<div><p>Epilepsy is a chronic neurological disorder featured by abnormal neural discharges that can lead to cognitive impairment. Salidroside (Sal), a biologically active component, protects neurons against various insults. The current study aims to explore the therapeutic potential of Sal in epilepsy and elucidate the mechanisms underlying its effects. We established a rat model of status epilepticus (SE) using pentylenetetrazol-kindling. SE rats were treated with Sal. Assessment of seizure latency and epileptic stage scores were performed. Cognitive function of rats was evaluated using a novel object recognition test and a Morris water maze test. Neuronal damage and hippocampal pathology were examined, alongside microglial and astrocyte activation, complement C3-C3a receptor (C3-C3aR) pathway involvement, and inflammatory factor levels. Sal prolonged seizure latency, decreased epilepsy stage scores, and improved cognitive performance compared to untreated SE rats. Furthermore, Sal suppressed the activation of C3-C3ar, microglia, and astrocytes, while decreasing the levels of inflammatory factors, which ameliorated hippocampal damage and neuronal loss. Sal may attenuate epilepsy and cognitive dysfunction by downregulating complement C3-C3aR pathway-mediated activation of microglia and astrocytes.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144880808","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}

{"title":"Jiao-Tai-Wan Improves Cognitive Impairment by Regulating Nrf2/ARE/HO-1 Signaling Pathway in APP/PS1 Mice","authors":"Xin-Chen Wang,&nbsp;Guang-Liang Wu,&nbsp;Hai-Yan Cai,&nbsp;Chen-Liang Chu,&nbsp;Yan-Lu Liu,&nbsp;Han-Cheng Li,&nbsp;Jing Zheng,&nbsp;Huangbao Chen,&nbsp;Hao Lin,&nbsp;Shi-Yong Li,&nbsp;Xin Chen","doi":"10.1007/s11064-025-04515-7","DOIUrl":"10.1007/s11064-025-04515-7","url":null,"abstract":"<div><p>Alzheimer’s disease (AD) is a chronic, progressive, and destructive neurodegenerative disorder that severely affects human memory, intelligence, and behavioral abilities. Jiao Tai Wan (JTW) is a classic formula composed of two traditional Chinese medicines, coptis chinensis (CC) and cinnamon (CIN), the ratio of CC and CIN is 10:1. JTW has the effects of promoting cognitive function, and improving learning and memory function. But the specific mechanism has not been systematically studied. We conducted Morris water maze and Y-maze behavioral tests, polymerase chain reaction (PCR), assay kit and ELISA, nissl’s staining, and western blotting to verified the improvement of cognitive function of JTW on APP/PS1 mice. Through behavioral experiments, JTW can improved the learning and spatial exploration abilities of APP/PS1 mice. Nissl’s staining and PCR detection of BDNF, NGF, and SYP showed that JTW can improved neurodegenerative lesions in APP/PS1 mice. By detecting the activities of A β 1–40, A β 1–42, α - secretase, β - secretase, and γ - secretase, as well as cholinergic labeling enzymes of Ach, AchE, and ChAT activities showed that JTW improved cerebral amyloidosis and cholinergic nervous system in APP/PS1 model mice. The detection of inflammatory factors and oxidative stress indicators revealed that JTW can inhibited the activity of inflammatory factors and oxidative stress. Western Blotting was used to detect the Nrf2/ARE/HO-1 pathway, and the result showed that JTW can regulate the Nrf2/ARE/HO-1 pathway to improving cognitive function of APP/PS1 mice. JTW enhanced the activity of Nrf2, regulated the Nrf2/ARE/HO-1 pathway, increased the activity of nerve growth factors, improved the cholinergic nervous system, inhibited inflammatory factors and oxidative stress, and ameliorated cognitive dysfunction in APP/PS1 mice.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861393","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}

{"title":"Progressive Blood–Brain Barrier Disruption in Sleep-Restricted Young Mice: Cellular Senescence and Neuroinflammation Crosstalk","authors":"Jessica J. Avilez-Avilez,&nbsp;Jesús Enrique García-Aviles,&nbsp;Ricardo Jair Ramírez-Carreto,&nbsp;Verónica Salas-Venegas,&nbsp;Mara A. Guzmán-Ruiz,&nbsp;Fernanda Medina-Flores,&nbsp;Mina Königsberg,&nbsp;Anahí Chavarría,&nbsp;Beatriz Gómez-González","doi":"10.1007/s11064-025-04510-y","DOIUrl":"10.1007/s11064-025-04510-y","url":null,"abstract":"<div><p>Sleep loss promotes a chronic low-grade inflammatory status with increased levels of inflammatory cytokines. Sleep loss also induces low-grade neuroinflammation characterized by glial reactivity and blood–brain barrier (BBB) dysfunction, as evidenced by BBB hyperpermeability and tight junction disassembly. Additionally, it raises molecules related to the senescence-associated secretory phenotype (SASP) in aged subjects, suggesting an increase in senescent cells. Here, we assessed the impact of sleep restriction on cellular senescence, neuroinflammation, and BBB function in the cerebral cortex and hippocampus of young male C57BL/6 mice. Sleep restriction induced a progressive increase in BBB permeability after 3, 5, and 10 days, along with a higher expression of the astroglial marker, the glial fibrillary acidic protein (GFAP), and the expression of the C3 complement component. The pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) increased in a region-dependent form. Furthermore, the progressive increase of the senescence markers β-galactosidase and p21 observed in both brain regions was accompanied by a neurotoxic astroglial response. Our data suggest that sleep restriction promotes cellular senescence in the cerebral cortex and hippocampus of young mice.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11064-025-04510-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861396","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}