Neuroscience Research最新文献

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 : 2025-10-01 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":"2025-10-01","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

Modeling natural neural networks of decision making with artificial neural networks 用人工神经网络建模自然神经网络的决策。

IF 2.3 4区医学

Neuroscience Research Pub Date : 2025-09-26 DOI: 10.1016/j.neures.2025.104961

Akihiro Funamizu , Ryo Karakida

{"title":"Modeling natural neural networks of decision making with artificial neural networks","authors":"Akihiro Funamizu , Ryo Karakida","doi":"10.1016/j.neures.2025.104961","DOIUrl":"10.1016/j.neures.2025.104961","url":null,"abstract":"<div><div>One main focus in neuroscience is to understand the relationship between decision making and various brain regions. Researchers use machine learning approaches to model the neural circuits of cerebral cortices, cerebellum, and basal ganglia. This review focuses on artificial neural networks (ANNs), particularly recurrent neural networks (RNNs), to model cortical functions for decision making. We first introduce the basic architecture of RNNs and explain how researchers compare the activity and circuits between artificial and biological networks. We also summarize how RNNs model the prefrontal and posterior parietal cortical in tasks involving short-term memory, perceptual decision making, and value-based decision making. We then show our recent challenges to develop a real-cyber hybrid network, that integrates neuronal activity in mice with RNN-based artificial units to better generate continuous-time body movements, compared to conventional RNNs that only use artificial units. The hybrid network tries to develop RNNs which have similar activity to the brain by using real neurons, rather than developing artificial RNNs and comparing their functions with biological brain. We propose that such integrative approaches in neuroscience and AI will further our understanding of both natural and artificial intelligence in the field of neuro-AI.</div></div>","PeriodicalId":19146,"journal":{"name":"Neuroscience Research","volume":"220 ","pages":"Article 104961"},"PeriodicalIF":2.3,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145186593","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 : 2025-09-23 DOI: 10.1016/j.neures.2025.104959

Tatsuya Manabe , Takashi Saito

引用次数: 0

Animal models of tau propagation in Alzheimer's disease 阿尔茨海默病中tau蛋白繁殖的动物模型。

IF 2.3 4区医学

Neuroscience Research Pub Date : 2025-09-23 DOI: 10.1016/j.neures.2025.104960

Masami Masuda-Suzukake, Shotaro Shimonaka, Takashi Nonaka, Masato Hasegawa

{"title":"Animal models of tau propagation in Alzheimer's disease","authors":"Masami Masuda-Suzukake, Shotaro Shimonaka, Takashi Nonaka, Masato Hasegawa","doi":"10.1016/j.neures.2025.104960","DOIUrl":"10.1016/j.neures.2025.104960","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is characterized by extracellular amyloid plaques composed of amyloid-β and intracellular neurofibrillary tangles composed of aggregated tau protein. In sporadic AD, the distribution of pathological tau progresses in a stereotypical manner and correlates with clinical staging, whereas the distribution of amyloid-β plaques does not. This suggests that the spread of tau pathology is a critical process that plays a key role in neurodegeneration and disease progression. Accurate models of tau propagation are therefore necessary to develop disease-modifying drugs for AD. The prion-like propagation hypothesis is a potential mechanism for the progressive distribution of tau pathology in the brain. In 2009, it was experimentally demonstrated that the intracerebral injection of brain extracts from transgenic mice that overexpress a mutated form of human tau protein into other tau transgenic mice induced the spread of pathological tau <em>in vivo</em>. Since then, this approach has been widely used to model tau propagation. More recently, newer models that more closely replicate the pathology of AD have been developed. This review summarizes the latest developments in animal models of tau propagation in sporadic AD.</div></div>","PeriodicalId":19146,"journal":{"name":"Neuroscience Research","volume":"220 ","pages":"Article 104960"},"PeriodicalIF":2.3,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150137","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 : 2025-09-19 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":"2025-09-19","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

Neurotransmitter receptor gene expression patterns associated with reward-related neural representations 神经递质受体基因表达模式与奖励相关的神经表征。

IF 2.3 4区医学

Neuroscience Research Pub Date : 2025-09-17 DOI: 10.1016/j.neures.2025.104957

Kaosu Matsumori , Kana Matsuyanagi , Kenji Matsumoto

{"title":"Neurotransmitter receptor gene expression patterns associated with reward-related neural representations","authors":"Kaosu Matsumori , Kana Matsuyanagi , Kenji Matsumoto","doi":"10.1016/j.neures.2025.104957","DOIUrl":"10.1016/j.neures.2025.104957","url":null,"abstract":"<div><div>The neural representation of reward is underpinned by neurotransmitter systems; however, current human neuroimaging techniques cannot assess the receptor-specific contributions to reward processing. We investigated the relationships between reward-related neural representations and the expression patterns of 30 neurotransmitter receptor genes by combining meta-analytic functional neuroimaging maps with gene expression data from the Allen Human Brain Atlas. Clustering analysis revealed that serotonin receptor 2 A was co-expressed with other reward-related receptors, whereas the nociceptin (NOP) receptor exhibited a distinct expression pattern. Using elastic net regression with spatial null models, we observed that monetary reward maps showed significant positive spatial correlations with serotonin receptor 2 A expression and negative correlations with NOP receptor expression. Similar positive correlations with serotonin receptor 2 A were observed in the craving maps. Principal component regression provided complementary evidence, with both monetary reward and craving maps showing significant associations with components characterized by NOP receptor loadings. These findings from multiple analytical approaches suggest that reward processing involves both coordinated receptor networks and specialized receptor systems, particularly highlighting the opposing roles of the serotonin receptor 2 A and NOP systems. Our results provide insights into the molecular mechanisms underlying reward processing in the human brain, potentially informing targeted interventions for reward-related disorders.</div></div>","PeriodicalId":19146,"journal":{"name":"Neuroscience Research","volume":"220 ","pages":"Article 104957"},"PeriodicalIF":2.3,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091940","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 : 2025-09-10 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":"2025-09-10","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

Differential representation of motivation and affective judgment by neurons in the primate ventral striatum and ventral pallidum during approach-avoidance decision-making 灵长类动物避近决策过程中腹侧纹状体和腹侧苍白球神经元对动机和情感判断的差异表征。

IF 2.3 4区医学

Neuroscience Research Pub Date : 2025-09-06 DOI: 10.1016/j.neures.2025.104955

Jung-min N. OH , Satoko Amemori , Masahiko Takada , Ken-ichi Amemori

{"title":"Differential representation of motivation and affective judgment by neurons in the primate ventral striatum and ventral pallidum during approach-avoidance decision-making","authors":"Jung-min N. OH , Satoko Amemori , Masahiko Takada , Ken-ichi Amemori","doi":"10.1016/j.neures.2025.104955","DOIUrl":"10.1016/j.neures.2025.104955","url":null,"abstract":"<div><div>Decision-making often involves evaluating trade-offs between potential rewards and aversive outcomes, engaging both motivational drive and affective judgment. The ventral striatum (VS) and ventral pallidum (VP) are key regions involved in these processes. While the VS is associated with reward processing and incentive motivation, the VP encodes hedonic value and mediates motivated behaviors. However, their distinct roles under conditions that involve both appetitive and aversive outcomes remain unclear. In this study, we recorded single-unit activity from the VS and VP in macaques performing alternating approach-approach and approach-avoidance tasks. We focused on two behaviorally derived variables: fixation error frequency (FoE), reflecting motivational engagement, and chosen value (ChV), representing subjective value based on cost-benefit evaluation. Our results revealed a functional dissociation: VS neurons rapidly adjusted cue-period activity in anticipation of aversive contexts, suggesting a role in modulating internal motivational states. By contrast, VP neurons changed more gradually, except for rapid outcome-locked responses to actual air-puff delivery, indicating their involvement in processing actual aversive events. Nonetheless, neurons in both regions consistently encoded FoE and ChV across tasks. These findings highlight the dynamic yet complementary contributions of the VS and VP to the representation of motivation and valuation during decision-making under aversive conditions.</div></div>","PeriodicalId":19146,"journal":{"name":"Neuroscience Research","volume":"219 ","pages":"Article 104955"},"PeriodicalIF":2.3,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145023847","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

Quantitative comparison of uncrossed corticospinal tracts arising from different cortical areas in humans 人类不同皮质区产生的未交叉皮质脊髓束的定量比较。

IF 2.3 4区医学

Neuroscience Research Pub Date : 2025-09-01 DOI: 10.1016/j.neures.2025.104954

Noboru Usuda, Sho K. Sugawara, Toshiki Tazoe, Yukio Nishimura

{"title":"Quantitative comparison of uncrossed corticospinal tracts arising from different cortical areas in humans","authors":"Noboru Usuda, Sho K. Sugawara, Toshiki Tazoe, Yukio Nishimura","doi":"10.1016/j.neures.2025.104954","DOIUrl":"10.1016/j.neures.2025.104954","url":null,"abstract":"<div><div>The uncrossed corticospinal tract (CST) has garnered interest as a potential compensatory neural pathway for recovering motor function after stroke-induced damage to the crossed CST. However, the area of origin of the uncrossed CST in humans remain unclear. This study aimed to identify the area of origin of the uncrossed CST in healthy adults via fibre tractography and diffusion-weighted magnetic resonance imaging. We identified uncrossed corticospinal (CS) streamlines arising from seven cortical areas: the primary motor cortex (M1: mean ± SE = 71.55 ± 2.19 %), primary somatosensory cortex (13.77 ± 2.18 %), supplementary motor area (SMA: 8.02 ± 1.49 %), dorsal (2.51 ± 0.52 %), and ventral (1.39 ± 0.31 %) aspects of the premotor cortex, preSMA (1.50 ± 0.42), and Brodmann area 5 (1.26 ± 0.21 %). Even though there was a fair amount of individual variation (min - max: 17.98–99.73 %), on average, 74.04 % of the CS streamlines passed through the dorsolateral funiculus of the spinal cord. Our findings enhance the anatomical understanding of the uncrossed CST and may inform neurorehabilitation strategies aimed at optimizing motor recovery following neurological injury.</div></div>","PeriodicalId":19146,"journal":{"name":"Neuroscience Research","volume":"219 ","pages":"Article 104954"},"PeriodicalIF":2.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993059","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

Morphologic changes in striatonigral neurons in a rat model of levodopa-induced dyskinesia 左旋多巴诱导运动障碍大鼠纹状体神经元形态学改变

IF 2.3 4区医学

Neuroscience Research Pub Date : 2025-08-28 DOI: 10.1016/j.neures.2025.104953

Masako Fujita , Haruo Nishijima , Tomonori Furukawa , Fumiaki Mori , Aogi Kobayashi , Chieko Suzuki , Koichi Wakabayashi , Masahiko Tomiyama

{"title":"Morphologic changes in striatonigral neurons in a rat model of levodopa-induced dyskinesia","authors":"Masako Fujita , Haruo Nishijima , Tomonori Furukawa , Fumiaki Mori , Aogi Kobayashi , Chieko Suzuki , Koichi Wakabayashi , Masahiko Tomiyama","doi":"10.1016/j.neures.2025.104953","DOIUrl":"10.1016/j.neures.2025.104953","url":null,"abstract":"<div><div>We aimed to elucidate morphological changes in striatonigral projection neurons in a rat model of levodopa-induced dyskinesia (LID). Male Wistar rats underwent unilateral 6-hydroxydopamine lesioning to establish a hemiparkinsonian model. At 8 weeks postoperatively, the rats were allocated to either the levodopa-treated group or the saline-treated control group. Behavioral abnormalities were quantified using the Abnormal Involuntary Movement (AIM) scores. We identified direct pathway neurons projecting to substantia nigra pars reticulata (SNr) by retrograde tracer injection. Dendritic spine morphology and the ultrastructure of synaptic terminals in SNr were assessed. The AIM scores increased along with levodopa treatment. Compared to control rats and the intact side of the LID model, the dendritic spine heads of striatonigral projection neurons were significantly enlarged, while spine density was reduced in the dopamine-denervated side of the LID model. Electron microscopic analysis revealed enlarged axon terminals and an increased number of synaptic vesicles in the dopamine-denervated side of SNr in levodopa-treated rats compared with those of the controls. Repeated levodopa administration induces morphological plasticity in striatonigral neurons, characterized by enlarged dendritic spine heads, reduced spine density, and enlarged synaptic terminals. These structural alterations likely contribute to enhanced GABAergic transmission in SNr and a reduced threshold for dyskinesia.</div></div>","PeriodicalId":19146,"journal":{"name":"Neuroscience Research","volume":"219 ","pages":"Article 104953"},"PeriodicalIF":2.3,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144925662","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