Neuroscience最新文献

{"title":"Chenodeoxycholic Acid-Mediated neuroprotection via α-synuclein and BDNF Modulation in MPTP-Induced mouse model of Parkinson’s disease","authors":"Mehwish Mehreen ,&nbsp;Mehak Ali ,&nbsp;Huraira Tariq ,&nbsp;Aneeqa Noor ,&nbsp;Sara Mumtaz ,&nbsp;Saima Zafar","doi":"10.1016/j.neuroscience.2025.03.050","DOIUrl":"10.1016/j.neuroscience.2025.03.050","url":null,"abstract":"<div><div>Parkinson’s disease (PD) remains a major challenge in the field of neurodegenerative diseases and requires innovative therapeutic approaches. In this study, we investigated the therapeutic potential of chenodeoxycholic acid (CDCA) in PD using a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model. CDCA, a naturally occurring bile acid, has previously shown promise in various neurological disorders by reducing neuronal degeneration and promoting neuronal health, however its utility in PD has not been studied. We divided mice into a control group, an MPTP-induced PD model and a treatment group injected with CDCA. CDCA reduced motor impairment and ameliorated anxiety-like behavior as assessed through the pole and open field test, demonstrated antidepressant effects in the forced swim and tail suspension test, and results of the Y-maze test showed improved cognitive performance. Furthermore, the effective defense against MPTP-induced dopaminergic degeneration was provided by CDCA by improving the morphological and histological features of neurons in the midbrain, hippocampus, cortex and cerebellum. Analysis via RT-PCR revealed that CDCA significantly mitigated MPP + -induced elevations in α-synuclein levels, indicating its potential to preserve neuronal function by modulating synaptic integrity. Additionally, CDCA effectively reduced the associated toxicity by enhancing the low levels of brain-derived neurotrophic factor. Conclusively, given the increasing prevalence of PD and the urgent need for effective neuroprotective strategies, our findings suggest that CDCA exerts neuroprotective effects in an MPTP-induced PD model. These results highlight CDCA as a promising candidate for further investigation in PD therapy and provide a basis for further research into bile acid-based treatments in neurodegenerative diseases.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"573 ","pages":"Pages 442-450"},"PeriodicalIF":2.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143784018","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":"Identifying blood mitochondrial DNA copy number as a biomarker for development of neurodegenerative diseases: Evidence from Mendelian randomization analysis","authors":"Shizhen Lei ,&nbsp;Yani Liu","doi":"10.1016/j.neuroscience.2025.04.003","DOIUrl":"10.1016/j.neuroscience.2025.04.003","url":null,"abstract":"<div><div>Mitochondrial dysfunction has been associated with neurodegenerative diseases (NDDs). This study aimed to explore the association between blood mitochondrial DNA copy number (mtDNA-CN) and development of NDDs. This study was based on two-sample Mendelian randomization (MR) analysis. The genome wide association study (GWAS) data of NDDs including Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), age-related macular degeneration (AMD), multiple sclerosis (MS), Parkinson’s disease (PD), primary open-angle glaucoma (POAG), and vascular dementia (VD) was obtained from FinnGen consortium. Inverse-variance weighted (IVW) was applied as the primary approach for MR estimation. MR results revealed that blood mtDNA-CN exhibited a significant relationship with the incidence of AD (IVW-P = 0.011, odds ratio [OR] = 0.65) and AMD (IVW-P = 0.038, OR = 0.64). However, there was no significant association observed between blood mtDNA-CN and other NDDs (IVW-P &gt; 0.05). Our findings supported the relationship between mitochondrial dysfunction and development of AD and AMD, and that blood mtDNA-CN may serve as a potential biomarker for the incidence of these two NDDs.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"573 ","pages":"Pages 421-429"},"PeriodicalIF":2.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143784010","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":"Unraveling the cGAS-STING pathway in Alzheimer’s disease: A new Frontier in neuroinflammation and therapeutic strategies","authors":"Arshdeep Kaur ,&nbsp;Khadga Raj Aran","doi":"10.1016/j.neuroscience.2025.04.001","DOIUrl":"10.1016/j.neuroscience.2025.04.001","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) is the most prevalent type of neurological disorder characterized by cognitive decline and memory loss, marked by the accumulation of amyloid beta (Aβ) plaques and hyperphosphorylated tau protein, causing extensive neuronal death and neuroinflammation. There is growing evidence that AD development extends beyond the neuronal compartment and has a major impact on the immunological functions of the brain. The cyclic GMP-AMP synthase (cGAS) detects cytosolic DNA, including pathogenic foreign DNA and self-DNA from cellular injury, triggering a type I interferon (IFN-I) response through activation of the stimulator of interferon genes (STING). The activation of the cGAS-STING pathway in response to mitochondrial dysfunction drives neuroinflammation in AD, which is mediated by the release of IFN-I cytokines. Furthermore, the release of oxidized mtDNA is necessary for the stimulation of the nucleotide-binding domain, leucine-rich–containing family, pyrin domain–containing-3 (NLRP3) inflammasome, which is a family of protein complexes that macrophages can produce to induce inflammation. AD becomes severe by the stimulation of the cGAS-STING pathway, which results in sterile inflammation and microglial dysfunction. This review aims to explore the potential impact of the cGAS-STING signaling pathway in the pathogenesis and progression of AD. Additionally; after overviewing recent findings, this article highlights the molecular mechanism involved in the onset of disease and its modulation regarding the therapeutic approach of AD. Finally, deliberated a deep insight, the cGAS-STING axis could provide novel therapeutic avenues for slowing or halting the progression of AD, thereby offering new prospects for treatment development.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"573 ","pages":"Pages 430-441"},"PeriodicalIF":2.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143784009","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":"Disentangling the Gordian Knot of parasympathetic innervations in arthritic joint","authors":"Sharon Mathew ,&nbsp;Stergios Boussios ,&nbsp;Saak V. Ovsepian","doi":"10.1016/j.neuroscience.2025.03.061","DOIUrl":"10.1016/j.neuroscience.2025.03.061","url":null,"abstract":"<div><div>Healthy synovial joints receive innervations exclusively from sensory and sympathetic axons. In arthritis, however, they acquire cholinergic innervations with parasympathetic effects. The origin of cholinergic fibres in inflamed joints remains elusive. Based on clinical and preclinical evidence, we propose two models explaining their rise: (1) through sprouting and invasion of cholinergic sympathetic or parasympathetic axons from the periosteum of juxta-articular bones and (2) via phenotypic switch of intrinsic sympathetic (norepinephrinergic) fibres of synovial joints to cholinergic. The widely acknowledged anti-inflammatory and immunosuppressants effects of parasympathetic drive suggests a protective role of the newly aquired cholinergic innervations in arthritic joints.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"573 ","pages":"Pages 518-520"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780718","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":"Spermidine attenuates microglial activation, neuroinflammation, and neuronal injury in rat model of vascular dementia","authors":"Xinyuan Zhao ,&nbsp;Dan Li ,&nbsp;Zirui Zhu ,&nbsp;Suzhen Li ,&nbsp;Yaze Qin ,&nbsp;Yi Yang","doi":"10.1016/j.neuroscience.2025.03.054","DOIUrl":"10.1016/j.neuroscience.2025.03.054","url":null,"abstract":"<div><div>Spermidine has been implicated to provide beneficial effects on cognitive function in several model organisms as well as older adults with mild and moderate dementia. Nevertheless, the potential impact of spermidine on learning and memory deficits in vascular dementia (VaD) remains largely unknown. Here, bilateral common carotid artery occlusion (BCCAo) was applied to induce chronic cerebral hypoperfusion in rats. We demonstrated that spermidine therapy improved the spatial learning performance in model animals, accompanied with decreased cerebral histopathologic injury and increased restored myelin basic protein (MBP) expression. Moreover, spermidine suppressed abnormal microglia activation, inhibited the excessive generation of proinflammatory mediators, such as tumor necrosis factor (TNF)α and inducible nitric oxide synthase (iNOS), and increased the anti-inflammatory cytokine transforming growth factor (TGF)β expression in rodent brain following hypoperfusion. Our findings indicated that spermidine alleviated cognitive impairments of rats after VaD-like injury possibly <em>via</em> suppressing microglia-modulated neuroinflammation and neuronal injury. These data may shed light on understanding the pathogenesis of VaD and point to the promising value of spermidine supplementation for cognition improvement.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"573 ","pages":"Pages 355-363"},"PeriodicalIF":2.9,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143746353","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":"Electroacupuncture ameliorates cognitive impairment and white matter injury in vascular dementia rats via activating HIF-1α/VEGF/VEGFR2 pathway","authors":"Yihan Yang ,&nbsp;Ting Rao ,&nbsp;Yijing Jiang ,&nbsp;Ying Zhan ,&nbsp;Jing Cheng ,&nbsp;Zihan Yin ,&nbsp;Ke Ma ,&nbsp;Xiaoling Zhong ,&nbsp;Xinran Guo ,&nbsp;Shanli Yang","doi":"10.1016/j.neuroscience.2025.03.063","DOIUrl":"10.1016/j.neuroscience.2025.03.063","url":null,"abstract":"<div><div>Vascular dementia (VaD) significantly impairs patients’ quality of life and imposes a major social and economic burden. Electroacupuncture (EA), a contemporary modification of traditional acupuncture, has demonstrated potential in improving cognitive function in VaD, particularly when applied at the Shenting and Baihui. However, the underlying mechanisms remain inadequately understood. Elucidating how EA ameliorates cognitive deficits is critical for validating its clinical application and advancing non-pharmacological interventions for neurodegenerative disorders. This study aimed to investigate the neuroprotective mechanisms of electroacupuncture at these acupoints on cognitive function in VaD rats. VaD was induced in male Sprague-Dawley rats through bilateral common carotid artery occlusion (BCAO), with sham rats serving as controls. Rats were subsequently divided into three groups: BCAO, BCAO + EA and BCAO + EA + YC-1 (a HIF-1α inhibitor). Electroacupuncture was applied to the Shenting and Baihui. Cerebral blood flow (CBF) was measured using dynamic susceptibility contrast functional MRI, and cognitive recovery was evaluated through the Morris water maze. Immunohistochemical analysis quantified myelin repair and angiogenesis, while expression of HIF-1α, VEGF and VEGFR2 in white matter was quantified using PCR and Western blot. The results indicated that electroacupuncture improved learning and memory, increased CBF, enhanced myelin recovery and promoted angiogenesis in VaD rats. The expression of HIF-1α, VEGF and VEGFR2 in the white matter was significantly elevated in VaD rats. Electroacupuncture at Shenting and Baihui activates the HIF-1α/VEGF/VEGFR2 pathway, enhances angiogenesis, white matter perfusion and myelin repair, thereby restoring cognitive function in VaD rats.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"573 ","pages":"Pages 364-380"},"PeriodicalIF":2.9,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143746354","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":"A review: From old drugs to new solutions: The role of repositioning in alzheimer’s disease treatment","authors":"Fawad Ali Shah ,&nbsp;Halima Qadir ,&nbsp;Jehan Zeb Khan ,&nbsp;Muhammad Faheem","doi":"10.1016/j.neuroscience.2025.03.064","DOIUrl":"10.1016/j.neuroscience.2025.03.064","url":null,"abstract":"<div><div>Drug repositioning or drug reprofiling, involves identifying novel indications for approved and previously abandoned drugs in the treatment of other diseases. The traditional drug discovery process is tedious, time-consuming, risky, and challenging. Fortunately, the inception of the drug repositioning concept has expedited the process by using compounds with established safety profiles in humans, and thereby significantly reducing costs. Alzheimer’s disease (AD) is a severe neurological disorder characterized by progressive degeneration of the brain with limited and less effective therapeutic interventions. Researchers have attempted to identify potential treatment of AD from existing drug however, the success of drug repositioning strategy in AD remains uncertain. This article briefly discusses the importance and effectiveness of drug repositioning strategies, the major obstacles in the development of drugs for AD, approaches to address these challenges, and the role of machine learning in identifying early markers of AD for improved management.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"576 ","pages":"Pages 167-181"},"PeriodicalIF":2.9,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753636","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":"Paroxetine ameliorates corticosterone-induced myelin damage by promoting the proliferation and differentiation of oligodendrocyte precursor cells","authors":"Jingjing Bu ,&nbsp;Yuan Liu ,&nbsp;Yufang Zhao ,&nbsp;Liming Liu ,&nbsp;Jiduo Shen ,&nbsp;Yucheng Li","doi":"10.1016/j.neuroscience.2025.03.065","DOIUrl":"10.1016/j.neuroscience.2025.03.065","url":null,"abstract":"<div><div>Depression is frequently associated with demyelination in the prefrontal cortex (PFC), and promoting remyelination can improve neuronal signaling and alleviate depressive symptoms. Paroxetine, a classic selective serotonin reuptake inhibitor (SSRI), is known to exert its antidepressant effects by increasing serotonin levels. However, its potential to alleviate myelin damage in depression remains unclear. A corticosterone (CORT)-induced mouse model of depression was used in this study. Myelin staining and transmission electron microscopy (TEM) were employed to assess myelin damage in the PFC, while immunofluorescence and western blot were performed to evaluate the expression of myelin-associated proteins. The primary oligodendrocyte precursor cells (OPCs) were cultured in vitro. The results demonstrated that paroxetine significantly alleviated CORT-induced depressive-like behaviors, including increased sucrose preference and spontaneous activity in the open field, while reduced immobility time in the tail suspension and forced swimming tests. Paroxetine also increased myelin thickness and restoring myelin integrity in the PFC. Moreover, paroxetine upregulated the expression of MBP, MAG, and neurofilament light chain protein (NFEL). Immunofluorescence analysis that paroxetine significantly increased the number of OPC (Olig2⁺/NG2⁺) and promoted OL differentiation (Olig2⁺/CC-1⁺), as well as upregulating the expression of PDGFRα. BrdU assays further confirmed that paroxetine enhanced OPC proliferation. In vitro, paroxetine significantly increased the viability of primary OPCs and promoted their proliferation and differentiation, with the most potent effect observed at 20 nM. These findings suggest that paroxetine alleviates CORT-induced myelin damage and improves depressive-like behaviors by promoting OPC proliferation and differentiation, providing new insights into its antidepressant mechanisms.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"573 ","pages":"Pages 344-354"},"PeriodicalIF":2.9,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143746352","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":"Comment on the Silverstein’s critiques of Lee’s TELC theory as a membrane potential generation mechanism","authors":"Hirohisa Tamagawa","doi":"10.1016/j.neuroscience.2025.03.049","DOIUrl":"10.1016/j.neuroscience.2025.03.049","url":null,"abstract":"","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"573 ","pages":"Page 381"},"PeriodicalIF":2.9,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143746355","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":"Neural basis of aggressive behavior toward newborns in Mice: Advances and future Challenges","authors":"Daniel E. Olazábal,&nbsp;Marcela Alsina-Llanes","doi":"10.1016/j.neuroscience.2025.03.062","DOIUrl":"10.1016/j.neuroscience.2025.03.062","url":null,"abstract":"<div><div>Infanticidal or pup-directed aggressive behavior is present in most species, including humans. It occurs in both reproductive and non-reproductive contexts and its incidence and biological basis may vary among species, strains, sex, and individual experiences. This review has two objectives: 1) to describe the most likely neural circuit that mediates aggressive behavior towards pups in mice, including hormonal, neuroendocrine and neurochemical changes that may increase the probability of attacking pups; and 2) to discuss whether aggressive behavior toward pups in mice is rewarding, an impulsive or predatory response, or a form of maltreatment or adaptive behavior. We propose a neural model to explain aggressive behavior towards pups and discuss evidence suggesting that infanticidal and pup-directed aggressive behavior, although hard-wired in the brain, can be blocked or inhibited by changing the experiences of the subject prior to the access to pups.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"574 ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753637","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}