{"title":"Systemic administrations of protamine heal subacute spinal cord injury in mice.","authors":"Tomoya Ozaki , Takahiro Sugie , Yuji Suzuki , Kenji Uchimura , Masumi Suzui , Kazuma Sakamoto , Michiko Shirane , Kenji Kadomatsu","doi":"10.1016/j.neures.2024.12.001","DOIUrl":"10.1016/j.neures.2024.12.001","url":null,"abstract":"<div><div>Spinal cord injury (SCI) results in damage to neural circuits that cause long-term locomotor and sensory disability. The objective of the present study is to evaluate whether a clinical drug, protamine, can be employed as a therapeutic agent for SCI. First, we examined the rescue effect of protamine on dystrophic endballs (DEs) cultured on a chondroitin sulfate (CS) gradient coating. Consequently, axons with DE, which are unable to grow through the CS barrier, resumed growth after protamine treatment and were able to pass through the barrier. In addition, we tested whether protamine resolves the DE phenotype, accumulation of autophagosomes. The results demonstrated that protamine has significantly reduced the density of LC3 in DEs. Subsequently, mice were administered 1 mg/kg protamine via the tail vein one week following a contusion injury to the thoracic spinal cord. The hindlimb movements of the mice were evaluated in order to assess the therapeutic effect of protamine. Eleven venous administrations of protamine improved the symptoms. The current study has demonstrated that protamine cancels the CS inhibitory effect on axonal regrowth. Administrations of protamine were observed to alleviate hindlimb motor dysfunction in SCI mice. Our results suggest an effective therapeutic agent for SCI and a possibility for drug repositioning. It would be of interest to see if protamine also exerts a therapeutic effect in brain injury.</div></div>","PeriodicalId":19146,"journal":{"name":"Neuroscience Research","volume":"212 ","pages":"Pages 11-19"},"PeriodicalIF":2.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Youzhi Ning , Yue Zhang , Tao Jiang , Jianguo Feng , Jian Zhan , Cehua Ou , Lu Wang
{"title":"LRP1-mediated p-tau propagation contributes to cognitive impairment after chronic neuropathic pain in rats","authors":"Youzhi Ning , Yue Zhang , Tao Jiang , Jianguo Feng , Jian Zhan , Cehua Ou , Lu Wang","doi":"10.1016/j.neures.2024.12.005","DOIUrl":"10.1016/j.neures.2024.12.005","url":null,"abstract":"<div><div>Trigeminal neuralgia (TN) is a prevalent chronic neuropathic pain syndrome characterized by severe pain, often accompanied by cognitive dysfunction and cerebral degeneration. However, its mechanisms remain poorly understood. Hyperphosphorylation of tau protein (p-tau) is often seen in neurodegenerative disorders such as Alzheimer's disease (AD). LRP1 expression on brain neurons and microglial cells is believed to facilitate the propagation of p-tau. We established a TN rat model via infraorbital nerve chronic constrictive injury (ION-CCI). Once the model was established, we investigated the association between p-tau and cognitive impairment in TN rats by evaluating behavioral and degenerative markers. During the initial phase, we noted an increase in p-tau level in the prefrontal cortex and hippocampal tissues of TN rats. The accompanied impaired learning and memory abilities suggested cognitive dysfunction. Blocking p-tau synthesis by orally administering a protein phosphatase and by injecting adenoviral vectors targeting LRP1 into the lateral ventricle of rats ameliorated cognitive impairment. This suggests that cognitive decline in TN rats is linked to elevated p-tau levels. Our findings show that LRP1-mediated p-tau propagation may drive cognitive impairment associated with neuropathic pain in TN rats.</div></div>","PeriodicalId":19146,"journal":{"name":"Neuroscience Research","volume":"212 ","pages":"Pages 84-96"},"PeriodicalIF":2.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thomas F. Münte , Annette Marek , Marcus Heldmann , Bernadette M. Jansma
{"title":"An event-related brain potential analysis of the use of temporal connectives in language production","authors":"Thomas F. Münte , Annette Marek , Marcus Heldmann , Bernadette M. Jansma","doi":"10.1016/j.neures.2024.12.007","DOIUrl":"10.1016/j.neures.2024.12.007","url":null,"abstract":"<div><div>This study investigates the cognitive and neural mechanisms involved in the linearization of events during language production, focusing on the processing of temporal conjunctions \"before\" and \"after.\" While natural language typically presents events in chronological order, non-chronological sequences, as required by \"before\" sentences, impose additional cognitive demands. Using an adapted network task, we recorded event-related potentials (ERPs) in 24 healthy German speaking participants to examine the brain activity associated with these demands. Results showed that \"before\" sentences elicited early positivity and later negativity in ERPs, particularly over left temporal and frontocentral regions, suggesting increased working memory requirements for reordering events. These findings align with previous behavioral and neuroimaging studies, indicating that both language production and comprehension of \"before\" sentences necessitate more complex cognitive processing than \"after\" sentences. This research highlights the significant role of working memory during the conceptualization stage of language production exemplified by the brain’s handling of non-chronological sequences.</div></div>","PeriodicalId":19146,"journal":{"name":"Neuroscience Research","volume":"212 ","pages":"Pages 69-74"},"PeriodicalIF":2.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Time-window of offline long-term potentiation in anterior cingulate cortex during memory consolidation and recall","authors":"Junyu Liu , Akihiro Goto , Yasunori Hayashi","doi":"10.1016/j.neures.2024.12.009","DOIUrl":"10.1016/j.neures.2024.12.009","url":null,"abstract":"<div><div>Episodic memories are initially formed in the hippocampus and subsequently transferred to cortical regions for long-term storage. This process, known as memory consolidation, involves plastic changes in synaptic transmission such as long-term potentiation (LTP). However, at what time points and specific locations LTP acts at remains unclear. We previously developed an optogenetic tool, cofilin-SuperNova (CFL-SN), that allows for the selective erasure of LTP within a limited time window. Using CFL-SN, here we show that the erasure of LTP in the anterior cingulate cortex (ACC) during sleep on the subsequent day, but not immediately following task acquisition, impairs recall of memory. However, allowing a single day without perturbation allowed memory to be recalled. Even after 7 days of repeated erasure of LTP, allowing LTP in the ACC on the 8th day restores memory recall. Once the memory is transferred, further LTP in the ACC is not necessary. Our findings indicates that the memory consolidation process completes in one sleep cycle and can occur at any timepoint up to 8th day.</div></div>","PeriodicalId":19146,"journal":{"name":"Neuroscience Research","volume":"212 ","pages":"Pages 75-83"},"PeriodicalIF":2.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143534815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Metformin alleviates auditory cell senescence by mitophagy induction.","authors":"Sung Il Cho, Eu-Ri Jo, Hee Sun Jang","doi":"10.1016/j.neures.2025.02.008","DOIUrl":"https://doi.org/10.1016/j.neures.2025.02.008","url":null,"abstract":"<p><p>Age-related hearing loss is the most common type of hearing loss in older adults. However, its underlying cellular mechanism is still unclear. Impaired mitochondrial function is a hallmark of various age-related pathologies. To maintain mitochondrial function in senescent cells, mitophagy is a crucial process for dysfunctional mitochondria turnover. Metformin has been reported to induce mitophagy. This study aimed to investigate the effect of metformin on preventing senescence in auditory cells. Low-dose H<sub>2</sub>O<sub>2</sub> represented senescence-associated secretory phenotype (SASP) and reduced mitophagy-related molecules in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells and cochlear explants. Metformin significantly decreased the expression of SASP in H<sub>2</sub>O<sub>2</sub>-induced senescent cells. Metformin also decreased the expression of senescence-associated p53 and p21, and increased the expression of mitophagy-related PINK1, Parkin, and BNIP3 in H<sub>2</sub>O<sub>2</sub>-induced senescent cells and cochlear explants. The co-localization of mitophagy dye and lyso dye decreased in H<sub>2</sub>O<sub>2</sub>-induced senescent cells, but metformin pre-treatment significantly increased their colocalization. Metformin significantly decreased the percentage of β-galactosidase-stained senescent cells and increased the expression of OXPHOS complexes in H<sub>2</sub>O<sub>2</sub>-induced senescent cells and cochlear explants. Metformin also significantly increased mitochondrial function in senescent cells. These results indicate that metformin prevented premature senescence in auditory cells by counteracting reduced mitophagy. Therefore, maintaining mitochondrial function using metformin might be a potential strategy for the prevention of age-related hearing loss.</p>","PeriodicalId":19146,"journal":{"name":"Neuroscience Research","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537471","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}
{"title":"Neuronal stress-coping mechanisms in postpartum females.","authors":"Yoshikage Muroi, Toshiaki Ishii","doi":"10.1016/j.neures.2025.02.006","DOIUrl":"10.1016/j.neures.2025.02.006","url":null,"abstract":"<p><p>Animals exhibit a wide range of stress responses aimed at restoring homeostasis and promoting adaptation. In response to stress, they employ coping mechanisms to maintain physiological balance. Dysregulated stress-coping strategies have been associated with mental disorders, including depression, anxiety, and post-traumatic stress disorder. Understanding the neuronal mechanisms that regulate stress-coping is critical for elucidating normal physiological responses and addressing the pathological processes underlying these disorders. Stress responses are influenced by sex and life stage, with notable variability in the prevalence and severity of mental disorders based on these factors. Stress-coping mechanisms are pivotal in determining the vulnerability or resilience of an individual to stress. Thus, identifying differences in stress-coping strategies between sexes and across life stages is essential for advancing prevention and treatment strategies for stress-related mental disorders. This review explores the neuronal mechanisms underlying stress responses, emphasizing the distinct stress-coping strategies utilized by postpartum females. Highlighting these differences underscores the need for targeted prevention and treatment approaches that consider sex- and life stage-specific variations in stress-coping mechanisms.</p>","PeriodicalId":19146,"journal":{"name":"Neuroscience Research","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468687","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}
{"title":"Bridge protein-mediated viral targeting of cells expressing endogenous μ-opioid G protein-coupled receptors in the mouse and monkey brain.","authors":"Riki Kamaguchi, Satoko Amemori, Ken-Ichi Amemori, Fumitaka Osakada","doi":"10.1016/j.neures.2025.02.007","DOIUrl":"10.1016/j.neures.2025.02.007","url":null,"abstract":"<p><p>Targeting specific cell types is essential for understanding their functional roles in the brain. Although genetic approaches enable cell-type-specific targeting in animals, their application to higher mammalian species, such as nonhuman primates, remains challenging. Here, we developed a nontransgenic method using bridge proteins to direct viral vectors to cells endogenously expressing μ-opioid receptors (MORs), a G protein-coupled receptor. The bridge protein comprises the avian viral receptor TVB, the MOR ligand β-endorphin (βed), and an interdomain linker. EnvB-enveloped viruses bind to the TVB component, followed by the interaction of βed with MORs, triggering viral infection in MOR-expressing cells. We optimized the secretion signals, domain arrangements, and interdomain linkers of the bridge proteins to maximize viral targeting efficiency and specificity. Alternative configurations incorporating different ligands and viral receptors also induced viral infection in MOR-expressing cells. The optimized βed-f2-TVB bridge protein with EnvB-pseudotyped lentiviruses induced infection in MOR-expressing cells in the striatum of mice and monkeys. An intersectional approach combining βed-f2-TVB with a neuron-specific promoter refined cell-type specificity. This study establishes the foundation for the rational bridge protein design and the feasibility of targeting G protein-coupled receptors beyond tyrosine kinase receptors, thereby expanding targetable cell types in the brain and throughout the body.</p>","PeriodicalId":19146,"journal":{"name":"Neuroscience Research","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425586","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}
{"title":"Subspace analysis identifies low-dimensional interactions between cortical and subcortical brain regions in social reward computation.","authors":"Hirokazu Tanaka, Masaki Isoda, Atsushi Noritake","doi":"10.1016/j.neures.2025.02.005","DOIUrl":"10.1016/j.neures.2025.02.005","url":null,"abstract":"<p><p>Animals living in social environments evaluate rewards given to themselves and others. We previously showed that single-unit activities in cortical (the medial prefrontal cortex, MPFC) and subcortical (the dopaminergic midbrain nuclei, DA, and the lateral hypothalamus, LH) regions reflect social reward computation. Extending the single-neuron analyses, this study employs matrix and tensor decomposition methods to characterize population activity within single regions and interactions between pairs of regions. First, we determined the dimensionality of population activity and corresponding components in a single brain region. The dimensions of MPFC and LH were comparable, indicating similarities in the population activities of the two regions. In contrast, the dimensions of DA were considerably smaller, indicating that the activities were idiosyncratic. Further, \"subspaces\" shared between MPFC and DA, between MPFC and LH, and between LH and DA were identified. We found that a few components in MPFC and LH explained a large portion of population activities in DA, indicating that the neural computation of social rewards resides in a small subspace. Our findings demonstrate that a limited number of neural components within cortico-subcortical circuits regulate the social monitoring of rewards to oneself and others.</p>","PeriodicalId":19146,"journal":{"name":"Neuroscience Research","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414159","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}
{"title":"Low-speed uphill exercise increases lactate and brain-derived neurotrophic factor in brain regions for memory and learning.","authors":"Masaki Takimoto, Taku Hamada","doi":"10.1016/j.neures.2025.02.004","DOIUrl":"10.1016/j.neures.2025.02.004","url":null,"abstract":"<p><p>We investigated the acute effects of low-speed uphill exercise on lactate levels and brain-derived neurotrophic factor (BDNF) expression in the cortex and hippocampus. Male Sprague Dawley rats were divided into control, flat exercise (flat-EX), and uphill exercise (uphill-EX). EX groups were subjected to treadmill EX at a low speed of 13 m/min for 30 min or 90 min on 0 % (flat-EX) or 40 % (uphill-EX) grades. Lactate levels in the blood and brain increased in the uphill-EX but not in the flat-EX. Despite the slow speed, uphill-EX decreased muscle glycogen, with a predominance of fast-twitch fibers; however, brain glycogen remained unchanged in both EX-groups. Sodium lactate was administered via external jugular catheterization to determine whether the uphill EX-induced brain lactate increase was derived from blood. Changes in blood lactate levels coincided with those in the brain, indicating that an elevation in blood lactate may lead to increased brain lactate levels. Furthermore, although a longer uphill exercise of 90 min increased BDNF protein levels in the cortex and hippocampus, the flat-EX did not cause a change. These results suggest that prolonged low-speed uphill exercise, which recruits fast-twitch muscles, acutely increases lactate and BDNF in the brain regions for memory and learning.</p>","PeriodicalId":19146,"journal":{"name":"Neuroscience Research","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399656","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}
Hao Peng, Qianqian Ge, Tianshuai Xu, Yifang He, Long Xu, Yi Yang, Sijin Wu, Jianghong He, Juanning Si
{"title":"Repetitive transcranial magnetic stimulation frequency influences the hemodynamic responses in patients with disorders of consciousness.","authors":"Hao Peng, Qianqian Ge, Tianshuai Xu, Yifang He, Long Xu, Yi Yang, Sijin Wu, Jianghong He, Juanning Si","doi":"10.1016/j.neures.2025.02.003","DOIUrl":"10.1016/j.neures.2025.02.003","url":null,"abstract":"<p><p>Repetitive transcranial magnetic stimulation (rTMS) emerges as a promising non-invasive neuromodulation technique for the treatment of patients with disorders of consciousness (DOC). The selection of rTMS parameters significantly influences the clinical therapeutic effects. However, the differences in spatiotemporal responsiveness of the brain under different rTMS stimulation frequencies remain unclear. In this pilot study, functional near-infrared spectroscopy (fNIRS) was used to evaluate the spatiotemporal differences in hemodynamic responses elicited by rTMS at different frequencies (1, 5, 10, 15, and 20 Hz) over left dorsolateral prefrontal cortex (F3). The results showed that the distribution patterns of the rTMS-evoked hemodynamic responses varied across different frequencies, indicating that rTMS frequency influences the hemodynamic responses in patients with DOC. Specifically, 10 Hz rTMS evoked strong positive hemodynamic responses over the frontal cortex, particularly in the right dorsolateral prefrontal cortex (R-DLPFC). Additionally, 20 Hz rTMS produced largepositive hemodynamic responses over the motor-related cortex, especially the right premotor cortex (R-PreM) and right primary sensorimotor cortex (PSMC). The current findings suggested that fNIRS can be used as a promising tool for evaluating the effects of rTMS in patients with DOC. Moreover, it provides useful guidance for the personalized design of rTMS parameters in a clinical environment.</p>","PeriodicalId":19146,"journal":{"name":"Neuroscience Research","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374324","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}