Neuroscience Research最新文献_第5页

Causal role of persistent neural activity in the mouse medial prefrontal cortex in promotion of wakefulness 小鼠内侧前额叶皮层持续神经活动在促进清醒中的因果作用。

IF 2.3 4区医学

Neuroscience Research Pub Date : 2025-12-01 Epub Date: 2025-10-16 DOI: 10.1016/j.neures.2025.104969

Sakiko Honjoh , Ayako Imamura , Saiko Akahira , Yoan Cherasse , Akiko Ihara , Takeshi Sakurai , Koichi Miyatake

{"title":"Causal role of persistent neural activity in the mouse medial prefrontal cortex in promotion of wakefulness","authors":"Sakiko Honjoh , Ayako Imamura , Saiko Akahira , Yoan Cherasse , Akiko Ihara , Takeshi Sakurai , Koichi Miyatake","doi":"10.1016/j.neures.2025.104969","DOIUrl":"10.1016/j.neures.2025.104969","url":null,"abstract":"<div><div>During wakefulness, cortical neurons fire tonically and asynchronously to constantly support ongoing cognitive functions, whereas they show synchronized cessation of firing, so called ‘OFF periods’, during NREM sleep. Previous studies reported that cortical neurons start showing local OFF periods even in awake animals as sleep pressure builds up during the course of sleep deprivation. However, spatio-temporal dynamics of OFF periods across the cerebral cortex during prolonged wakefulness remained unknown. In this study, our extracellular recording in free-behaving mice showed that prolonged wakefulness causes neuronal firing lapses in the medial prefrontal cortex (mPFC) but not in motor cortex, suggesting the importance of mPFC in maintaining cognition during wakefulness. We next examined cortical area-specific effects of sustained neural activation on vigilance states. Chemogenetic activation of excitatory neurons in mPFC, but not in motor or sensory cortex, promoted wakefulness. Additionally, chemogenetic inhibition of mPFC reduced time spent in wakefulness, further supporting the causal role of mPFC in wakefulness.</div></div>","PeriodicalId":19146,"journal":{"name":"Neuroscience Research","volume":"221 ","pages":"Article 104969"},"PeriodicalIF":2.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145318603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Traumatic brain injury and Alzheimer’s disease related neurodegenerative diseases: Insights from animal models 创伤性脑损伤和阿尔茨海默病相关的神经退行性疾病：来自动物模型的见解。

IF 2.3 4区医学

Neuroscience Research Pub Date : 2025-12-01 Epub Date: 2025-11-01 DOI: 10.1016/j.neures.2025.104979

Xinyi Zhao , Zhuohao He

{"title":"Traumatic brain injury and Alzheimer’s disease related neurodegenerative diseases: Insights from animal models","authors":"Xinyi Zhao , Zhuohao He","doi":"10.1016/j.neures.2025.104979","DOIUrl":"10.1016/j.neures.2025.104979","url":null,"abstract":"<div><div>Alzheimer’s disease and related neurodegenerative diseases (ADRD) represent a major global public health challenge, with their disease mechanisms remain largely unknown, and few treatments are available. Increasing epidemiological evidence underscores the critical role of traumatic brain injury (TBI) in the initiation and progression of ADRD, suggesting shared pathogenic mechanisms between these conditions. While there are still lack of perfect AD models in the field, TBI models may serve as useful and alternative platforms for investigating ADRD. In this review we delineate the definition and epidemiological characteristics of TBI. We further briefly compare the major experimental TBI animal models, outlining their respective strengths and limitations in replicating human neuropathology. Finally, we provide our perspective on potential mechanistic links between TBI and ND, including axonal injury, calcium homeostasis dysregulation, mitochondrial dysfunction, chronic neuroinflammation, blood-brain barrier disruption, and genetic susceptibility. We believe advancing preclinical and translational research on TBI not only enhances our understanding of the pathogenesis in ADRD but also holds promise for developing interventions to mitigate long-term consequences and improving clinical outcomes for many neurodegenerative diseases.</div></div>","PeriodicalId":19146,"journal":{"name":"Neuroscience Research","volume":"221 ","pages":"Article 104979"},"PeriodicalIF":2.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145438428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Diurnal modulation of optogenetically evoked neural signals 光遗传诱发的神经信号的昼夜调节。

IF 2.3 4区医学

Neuroscience Research Pub Date : 2025-12-01 Epub Date: 2025-10-31 DOI: 10.1016/j.neures.2025.104981

Yuki Donen , Yoko Ikoma , Ko Matsui

{"title":"Diurnal modulation of optogenetically evoked neural signals","authors":"Yuki Donen , Yoko Ikoma , Ko Matsui","doi":"10.1016/j.neures.2025.104981","DOIUrl":"10.1016/j.neures.2025.104981","url":null,"abstract":"<div><div>Neural signal processing in the cerebral cortex is often regarded as robust and stereotyped; however, the brain’s internal environment undergoes dynamic fluctuations across the day. Whether these diurnal rhythms modulate cortical responsiveness and plasticity remains unclear. Here, we examined diurnal modulation of neural responsiveness and plasticity in the primary visual cortex (V1). Using transgenic rats expressing channelrhodopsin-2 (ChR2), we optically stimulated V1 neurons with brief light pulses and recorded local field potentials (LFPs) over several days. V1 responses to single-pulse stimulation showed clear diurnal variation, with delta- and gamma-band activity modulated in a time-of-day–dependent manner. Administration of the adenosine A1 receptor antagonist DPCPX enhanced neural responses at Zeitgeber time (ZT) 0 (Sunrise) but not at ZT 12 (Sunset). LTP-like potentiation was observed only when train stimulation was applied at Sunrise, indicating that plasticity is also gated by diurnal phase. These findings demonstrate that both excitability and plasticity of V1 circuits are regulated by diurnal factors. Although it remains unclear whether these effects are driven by intrinsic circadian rhythms or light/dark-triggered mechanisms, our results highlight that cortical processing is dynamically modulated across the day, with implications for sensory function, learning, and neuromodulatory regulation.</div></div>","PeriodicalId":19146,"journal":{"name":"Neuroscience Research","volume":"221 ","pages":"Article 104981"},"PeriodicalIF":2.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145431831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Fluoxetine enhances the treatment of depression linked to opioid-induced constipation in mice by influencing the metabolomic profile 氟西汀通过影响代谢组学特征来增强与阿片类药物引起的便秘相关的小鼠抑郁症的治疗。

IF 2.3 4区医学

Neuroscience Research Pub Date : 2025-12-01 Epub Date: 2025-11-08 DOI: 10.1016/j.neures.2025.104983

Chun Wang , Shiqin Yao , Bowen Tian , Zhifeng Zhao , Yanrong Wang , Xiaoliang Li , Xuzhao Li , Qinxian Huang

{"title":"Fluoxetine enhances the treatment of depression linked to opioid-induced constipation in mice by influencing the metabolomic profile","authors":"Chun Wang , Shiqin Yao , Bowen Tian , Zhifeng Zhao , Yanrong Wang , Xiaoliang Li , Xuzhao Li , Qinxian Huang","doi":"10.1016/j.neures.2025.104983","DOIUrl":"10.1016/j.neures.2025.104983","url":null,"abstract":"<div><div>This study was intended to verify the potential role of Fluoxetine (Flx) in treating depression associated with opioid-induced constipation (OIC). We established a mouse model of chronic unpredictable mild stress (CUMS) and used loperamide to induce constipation based on the CUMS mice, generating a mouse model of depression associated with OIC (CUMS+OIC). The depressive behavior was evaluated via the open field and sucrose preference tests, while constipation was evaluated using defecation frequency and fecal water content. Liquid chromatography-mass spectrometry (LC-MS)-based metabolomics and bioinformatics analyses were performed. Treatment with Flx alleviated the depressive behavior of mice and inhibited OIC. We identified 153 differential metabolites between the control and the CUMS+OIC groups, among which 51 were downregulated while the other 102 were upregulated. These metabolites were involved in metabolic pathways such as pyrimidine metabolism, purine metabolism, and beta-alanine metabolism. Moreover, 64 differential metabolites between the Flx and the CUMS+OIC groups were involved in nicotinate and nicotinamide metabolism, and prion disease metabolism metabolic pathways. Through cluster analysis, we identified metabolites deregulated by CUMS+OIC and restored by Flx. Conclusively, Flx can improve the behavior and metabolic profile changes of CUMS associated with OIC, providing a basis for treating depression-related constipation.</div></div>","PeriodicalId":19146,"journal":{"name":"Neuroscience Research","volume":"221 ","pages":"Article 104983"},"PeriodicalIF":2.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145489284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Advances in non-human primate models for Alzheimer's disease research 非人类灵长类动物阿尔茨海默病研究的进展。

IF 2.3 4区医学

Neuroscience Research Pub Date : 2025-12-01 Epub Date: 2025-11-08 DOI: 10.1016/j.neures.2025.104984

Daisuke Joho , Kenya Sato , Wakako Kumita , Takaomi C. Saido , Erika Sasaki , Hiroki Sasaguri

{"title":"Advances in non-human primate models for Alzheimer's disease research","authors":"Daisuke Joho , Kenya Sato , Wakako Kumita , Takaomi C. Saido , Erika Sasaki , Hiroki Sasaguri","doi":"10.1016/j.neures.2025.104984","DOIUrl":"10.1016/j.neures.2025.104984","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) is the most common progressive neurodegenerative disease. It is characterized by cognitive decline and brain pathology, including amyloid-β (Aβ) plaques, neurofibrillary tangles, and neuroinflammation. While rodent models have contributed to our understanding of a multiplicity of disease mechanisms, their limitations in replicating human age-related neurodegenerative diseases pose challenges for translating research findings to the clinical setting. The common marmoset (<em>Callithrix jacchus</em>), a small non-human primate, has emerged as a promising model for neuroscience and aging research. Age-related Aβ and tau pathologies develop naturally in the marmoset, which also possess a brain network organization, including a default mode network, that closely resembles that of humans. AD-related pathologies have also been experimentally induced in marmosets through injection of materials extracted from post-mortem brain tissue of AD patients. Recent advances in genome-editing technologies have enabled the development of marmoset models carrying familial AD mutations. These models offer new opportunities to investigate early pathological changes in the disease and to evaluate potential therapeutic agents. Taken together, these findings highlight the value of the marmoset as a translational model bridging the gap between rodent studies and human AD research.</div></div>","PeriodicalId":19146,"journal":{"name":"Neuroscience Research","volume":"221 ","pages":"Article 104984"},"PeriodicalIF":2.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145489271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Axonal sprouting from adjacent dorsal root ganglia following cervical dorsal root avulsion in mice 小鼠颈背根撕脱后邻近背根神经节轴突萌发。

IF 2.3 4区医学

Neuroscience Research Pub Date : 2025-11-01 Epub Date: 2025-10-16 DOI: 10.1016/j.neures.2025.104971

Gaku Kanemoto , Takahide Itokazu , Toru Nakanishi , Takeru Furumiya , Seiji Okada , Toshihide Yamashita

{"title":"Axonal sprouting from adjacent dorsal root ganglia following cervical dorsal root avulsion in mice","authors":"Gaku Kanemoto , Takahide Itokazu , Toru Nakanishi , Takeru Furumiya , Seiji Okada , Toshihide Yamashita","doi":"10.1016/j.neures.2025.104971","DOIUrl":"10.1016/j.neures.2025.104971","url":null,"abstract":"<div><div>Brachial plexus injury is a neurological injury caused by trauma, and effective treatments remain limited. Understanding its pathology is necessary to develop new therapeutic strategies. In this study, we used a dorsal root avulsion mouse model to determine whether injury-induced alterations in feedback circuitry from the dorsal root ganglion (DRG) to motor neurons contribute to functional recovery. We visualized axons originating from DRG neurons by directly injecting adeno-associated virus encoding green fluorescent protein (AAV-GFP) into the DRG adjacent to the injury site and analyzed the total length of axons on the lateral side of the ventral horn in the spinal cord. Following injury, the fine motor function of the affected forepaw was immediately impaired and then gradually recovered. In parallel, axons originating from an adjacent, uninjured DRG extended into the deafferented spinal segments, possibly contributing to the reinnervation of motor neurons that had lost their original sensory input. Indeed, after spontaneous motor recovery, when we performed an additional dorsal root avulsion originating from the adjacent DRG, functional impairment of the forepaw re-emerged. Our results demonstrate that the plasticity of the adjacent DRG may facilitate the recovery of fine motor function after dorsal root injury.</div></div>","PeriodicalId":19146,"journal":{"name":"Neuroscience Research","volume":"220 ","pages":"Article 104971"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145318602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Hindering tau fibrillization by disrupting transient precursor clusters 干扰瞬态前体簇阻碍Tau纤化。

IF 2.3 4区医学

Neuroscience Research Pub Date : 2025-11-01 Epub Date: 2025-10-01 DOI: 10.1016/j.neures.2025.104968

Tomomi Takahashi , Takashi Nonaka , Reiko Ohtani , Masato Hasegawa , Yukiko Hori , Taisuke Tomita , Rei Kurita

{"title":"Hindering tau fibrillization by disrupting transient precursor clusters","authors":"Tomomi Takahashi , Takashi Nonaka , Reiko Ohtani , Masato Hasegawa , Yukiko Hori , Taisuke Tomita , Rei Kurita","doi":"10.1016/j.neures.2025.104968","DOIUrl":"10.1016/j.neures.2025.104968","url":null,"abstract":"<div><div>Tau protein, a central player in Alzheimer’s disease (AD), exhibits cytotoxicity upon ﬁbril formation. Understanding the early stages of tau ﬁbrillization is therefore critical for the development of eﬀective therapeutics. Previous work [Rasmussen. et. al, J. Mol. Biol., 2023] reported the rapid formation of Thioﬂavin T (ThT)-inactive clusters upon mixing tau with anionic polymers, yet the functional role of these clusters remained unclear. Here, we demonstrate that these transient clusters act as obligatory precursors in the ﬁbrillization pathway. Using small-angle X-ray scattering (SAXS) and ThT ﬂuorescence, we show that disrupting the clusters via NaCl addition hinders ﬁbril formation, highlighting their reversible and targetable nature. This behavior is analogous to polymer crystallization, in which disordered chains undergo structural ordering through intermediate precursor states. We propose that similar physical principles underlie the aggregation of other intrinsically disordered proteins such as <em>α</em>-synuclein.</div></div>","PeriodicalId":19146,"journal":{"name":"Neuroscience Research","volume":"220 ","pages":"Article 104968"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

The modified spatial context memory test for assessing cognitive aging in middle-aged and older adults 改进空间情境记忆测验评估中老年人认知老化。

IF 2.3 4区医学

Neuroscience Research Pub Date : 2025-11-01 Epub Date: 2025-09-10 DOI: 10.1016/j.neures.2025.104956

Hsuan-Min Wang , Yo-Ping Huang , Hsun-Yu Kuo , Hung-Chou Kuo

{"title":"The modified spatial context memory test for assessing cognitive aging in middle-aged and older adults","authors":"Hsuan-Min Wang , Yo-Ping Huang , Hsun-Yu Kuo , Hung-Chou Kuo","doi":"10.1016/j.neures.2025.104956","DOIUrl":"10.1016/j.neures.2025.104956","url":null,"abstract":"<div><div>Deficits in spatial-context memory may be risk factors for Alzheimer disease (AD). This study aimed to investigate spatial-context memory and spatial navigation in middle-aged and older adults using a modified spatial-context memory test (SCMT). This prospective study recruited adults aged 55–75 years from our outpatient department. Non-dementia cases were confirmed by neurologists and assessed by psychologists. Age and education were analyzed as continuous variables using regression models to examine their associations with SCMT performance. A modified SCMT was established, consisting of a computer program that performed in cooperation with a spatial memory paradigm using real-world simulation. Subtests of navigation, scene-event associations and people-object associations were included. Of 147 participants, 108 met the selection criteria and were included in the analysis. Older age was linked to more errors and longer retrieval times, whereas higher education was related to shorter completion times in some SCMT-I tasks. In conclusion, SCMT-I performance was primarily influenced by age, with older participants showing increased errors and longer retrieval times across subtests. These findings suggest that age-related changes in spatial-context memory can be detected even among cognitively normal adults, and that SCMT-I may provide a sensitive tool for assessing cognitive aging independent of educational background.</div></div>","PeriodicalId":19146,"journal":{"name":"Neuroscience Research","volume":"220 ","pages":"Article 104956"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145054864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Abnormalities in the functional activity of neural networks in a human iPSC model of Dravet syndrome Dravet综合征人类iPSC模型中神经网络功能活动异常。

IF 2.3 4区医学

Neuroscience Research Pub Date : 2025-11-01 Epub Date: 2025-09-19 DOI: 10.1016/j.neures.2025.104958

Ropafadzo Mzezewa , Tanja Hyvärinen , Oskari Kulta , Andrey Vinogradov , Emma Pesu , Lotta Isosaari , Valtteri Vuolanto , Fikret Emre Kapucu , Jens Schuster , Niklas Dahl , Susanna Narkilahti

{"title":"Abnormalities in the functional activity of neural networks in a human iPSC model of Dravet syndrome","authors":"Ropafadzo Mzezewa , Tanja Hyvärinen , Oskari Kulta , Andrey Vinogradov , Emma Pesu , Lotta Isosaari , Valtteri Vuolanto , Fikret Emre Kapucu , Jens Schuster , Niklas Dahl , Susanna Narkilahti","doi":"10.1016/j.neures.2025.104958","DOIUrl":"10.1016/j.neures.2025.104958","url":null,"abstract":"<div><div>Dravet syndrome (DS) is a severe pediatric epilepsy primarily caused by <em>de novo</em> mutation in the <em>SCN1A</em> gene encoding the alpha subunit of the voltage-gated sodium channel. While early <em>in vivo</em> studies linked DS pathology to GABAergic disinhibition, recent studies report altered sodium currents in both inhibitory and excitatory neurons. <em>In vitro</em> models containing both neuronal subtypes may offer deeper insights into functionality of neuronal networks. This study examined the effects of two different <em>SCN1A</em> pathogenic variants on the functional phenotype of human induced pluripotent stem cell -derived enriched GABAergic cultures and heterogeneous GABA- and glutamatergic cultures using microelectrode arrays. We observed functional differences evident as increased network bursts in one DS patient line compared to controls and to another DS patient line in GABAergic and heterogenous cultures. Importantly, heterogeneous cultures revealed lower spiking and bursting frequency in both DS patient lines. Principal component analysis confirmed distinct clustering of the functional profiles of the DS patient and control networks in heterogeneous cultures. The magnitude of the altered functional activity reflected the clinical severity of the disease. Thus, functional alterations caused by <em>SCN1A</em> variants are apparent in heterogenous cultures indicating their competence for characterizing disease phenotypes in DS.</div></div>","PeriodicalId":19146,"journal":{"name":"Neuroscience Research","volume":"220 ","pages":"Article 104958"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

A decade progress in the phenotyping of AppNL-G-F knock-in mouse model of Alzheimer’s disease apnl - g - f敲入小鼠阿尔茨海默病模型的表型研究进展

IF 2.3 4区医学

Neuroscience Research Pub Date : 2025-11-01 Epub Date: 2025-09-23 DOI: 10.1016/j.neures.2025.104959

Tatsuya Manabe , Takashi Saito

引用次数: 0