Neuroscience Letters最新文献

{"title":"Ventral tegmental area functional connectivity as a marker of resilience to sleep deprivation","authors":"Jungwon Cha,&nbsp;Kathryn E.R. Kennedy,&nbsp;David Negelspach,&nbsp;Alisa Huskey,&nbsp;William D.S. Killgore","doi":"10.1016/j.neulet.2025.138271","DOIUrl":"10.1016/j.neulet.2025.138271","url":null,"abstract":"<div><h3>Objective</h3><div>Sleep deprivation (SD) impairs cognitive functions like attention and reaction speed, though some individuals exhibit a trait-like resilience to these effects. To explore the neurobiological basis of this resilience, we quantified cognitive performance using the Percentage Reaction Speed Change (PRSC) from the psychomotor vigilance test (PVT). We then examined the relationship between PRSC and ventral tegmental area (VTA) functional connectivity during 28 h of SD.</div></div><div><h3>Methods</h3><div>Forty-four healthy adults (21 females; age = 25.4 ± 5.6 years) underwent a resting-state functional MRI (rs-fMRI) to examine whole-brain VTA connectivity. Within the same week, participants completed a 28-hour SD protocol, during which PVT performance was measured. We examined the association between VTA connectivity and PRSC, with a focus on connections to the Primary Visual Cortex (V1) and Supplementary and Cingulate Eye Field (SCEF).</div></div><div><h3>Results</h3><div>Greater VTA connectivity with the V1 and SCEF was associated with higher PRSC, suggesting that stronger VTA connectivity to these visual processing and cognitive control regions supports cognitive resilience to SD.</div></div><div><h3>Conclusion</h3><div>The VTA contributes to cognitive resilience during sleep deprivation through its connectivity with visual and cognitive control regions. These findings provide insight into neural mechanisms that help preserve cognitive performance under SD.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"859 ","pages":"Article 138271"},"PeriodicalIF":2.5,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128299","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":"Changes in gene expression of D2 and D5 receptors in the thalamus and midbrain caused by a persistent painful stimulus in Parkinsonian rats","authors":"José Luis Cortes-Altamirano ,&nbsp;Alfonso Alfaro-Rodríguez ,&nbsp;Abril Morraz-Varela ,&nbsp;Samuel Reyes-Long","doi":"10.1016/j.neulet.2025.138270","DOIUrl":"10.1016/j.neulet.2025.138270","url":null,"abstract":"<div><div>Pain is the most common and underdiagnosed non-motor symptom in Parkinson’s disease. Dopaminergic receptors D2 and D5 have been implicated in pain modulation. In this study, the expression of D2 and D5 receptors in the midbrain and thalamus in response to a painful stimulus was evaluated. The animals were assigned to a 6-OHDA group, a Sham group and a Control group. 6-OHDA was administered to the experimental group and 2 μl of 1 % ascorbic acid to the Sham group in the substantia nigra pars compacta. The midbrain and thalamus were dissected for RT-qPCR. In the formalin test, phase 1 showed significant differences between the Sham, 6-OHDA and Control groups, while in phase 2 the 6-OHDA group presented a greater nociceptive response. In the cylinder test, the 6-OHDA group showed a reduction in the use of the left limb and both limbs. In the open-field test, the 6-OHDA group spent more time in corners and showed less exploration in the periphery and center. An increasing trend for D5 was observed in the midbrain of the 6-OHDA group and in the thalamus of the Sham group. Dopaminergic injury induced by 6-OHDA as part of the parkinsonian model alters motor function, increases anxiety, and increases nociceptive response in the persistent phase of the formalin model. In addition, a non-significant increase in D5 receptor expression in the midbrain and thalamus may suggest an adaptive response of dopaminergic signaling to persistent pain.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"859 ","pages":"Article 138270"},"PeriodicalIF":2.5,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144098530","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":"The leptin/BDNF/TrkB signaling pathway improves corticosteroid combined with chronic restraint stress-induced depressive-like behavior in mice","authors":"Yunqian Ke,&nbsp;Yiming Wang,&nbsp;Yongxue Hu","doi":"10.1016/j.neulet.2025.138268","DOIUrl":"10.1016/j.neulet.2025.138268","url":null,"abstract":"<div><div>This study explored the effect and mechanism of leptin on depressive-like behavior induced by chronic corticosterone injections combined with chronic restraint stress (CORT-CRS) in mice. Differentially expressed genes (DEGs) were extracted using the Gene Expression Omnibus database and Sangerbox tool. Construct protein–protein interaction networks of target DEGs using Cytoscape software, and hub genes brain-derived neurotrophic factor (<em>BDNF</em>) were identified. A mouse model of depression was established using CORT-CRS. Behavioral changes were detected in the mice using the tail suspension, forced swimming, sugar water preference (SPT), and open field tests (OFT). Serum inflammatory factors were measured by Enzyme-linked immunosorbent assay (ELISA). Western blotting was used to detect the protein expression levels of BDNF and tyrosine kinase receptor B (TrkB). Immunofluorescence was used to detect hippocampal neurogenesis in each mouse group. Compared with the control group, mice in the CORT-CRS group presented with marked depression-like behavior and a higher interleukin (IL) -6, IL-1 β, tumor necrosis factor alpha (TNF – α) concentration. Different doses of leptin reversed depressive-like behavior in the CORT-CRS model mice, with significantly increased levels of BDNF, TrkB protein expression (<em>P</em> &lt; 0.01).</div><div>Furthermore, leptin promoted hippocampal neurogenesis in CORT-CRS-treated mice in vivo. Consequently, leptin alleviates CORT-CRS-induced depression-like behavior in mice by stimulating hippocampal neurogenesis. One possible mechanism could be related to the activation of the BDNF/TrkB signaling pathway, which could pave way for novel therapeutic targets that can be explored to prevent and treat depression.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"859 ","pages":"Article 138268"},"PeriodicalIF":2.5,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102073","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":"The expression of connexin 36 and 43 in animal models of trait and state anxiety","authors":"Mohammadreza Alizadeh ,&nbsp;Sahel Motaghi ,&nbsp;Mahya Moradi Sirchi ,&nbsp;Mehdi Abbasnejad ,&nbsp;Saeed Esmaili-Mahani","doi":"10.1016/j.neulet.2025.138269","DOIUrl":"10.1016/j.neulet.2025.138269","url":null,"abstract":"<div><div>Few studies have investigated the role of gap junctions in anxiety. Gap junctions (GJs) are intercellular channels, and their subunit are connexins (CXs). The specific isoforms of connexins for neurons and astrocytes are CX36, and CX43 respectively. Neuronal CX36 and astrocytic CX43 are critical for brain synchrony and homeostasis. Elevated plus maze (EPM) was used for animal models of trait and state anxiety. The gene expression was assessed by Real-time PCR technique in the ventral hippocampus (v Hip), basolateral amygdala (BLA), and medial prefrontal cortex (m PC). The rats were grouped as follows (n = 6): control, trait anxiety, in which the rats were placed in the EPM apparatus, state anxiety, in which the animals were placed in the EPM apparatus after tolerating 120 min of isolation. The data showed that the anxiety of the animals in the state anxiety group was significantly greater than the trait anxiety group (<em>p &lt; 0.05</em>). In the state anxiety animals, the gene expression of CX36 was lower in the m PC and BLA regions than the control and trait anxiety groups (<em>p &lt; 0.01</em>). CX43 expression in the BLA, and v Hip structures was also lower than in the control and trait anxiety groups. These findings suggest that downregulation of CX36 and CX43 contributes to state anxiety pathophysiology, highlighting GJs as potential therapeutic targets.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"859 ","pages":"Article 138269"},"PeriodicalIF":2.5,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102069","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":"Chronic administration of 1,3-di-o-tolylguanidyne induces catalepsy and reduces immobility responses by clamping and grasping in Wistar rat, evaluation in vivo and in silico","authors":"Dulce E. Nicolás-Álvarez ,&nbsp;José Luna-Muñoz ,&nbsp;Vicente Sandoval-Herrera ,&nbsp;Martha A. Estrada-Silva ,&nbsp;Javier Cruz-Rodríguez ,&nbsp;Nabil I. Luna-Viramontes ,&nbsp;Brenda Granados-Rivas ,&nbsp;Gabriela Silva-Luna ,&nbsp;Jimena Natalia Torres-Mendoza ,&nbsp;Hiram Tendilla-Beltrán ,&nbsp;Gonzalo Flores ,&nbsp;Linda Garcés-Ramírez ,&nbsp;Fidel de la Cruz-López","doi":"10.1016/j.neulet.2025.138267","DOIUrl":"10.1016/j.neulet.2025.138267","url":null,"abstract":"<div><div>Catalepsy, used to assess antipsychotic effects in animal models, involves sustained abnormal postures and resistance to displacement through balance reflexes. In contrast, immobility is a passive, stimulus-induced state marked by reduced movement and responsiveness, it can be triggered by a variety of stimuli. We found that a single administration of 1,3-di-o-tolylguanidine (DTG) had no effect on catalepsy, whereas daily administration induced cataleptic behavior by day 21. DTG reduced dorsal (grasping) and clamping immobility from the first day of administration, and this reduction persisted through day 21. Our findings support the potential use of sigma receptors as targets for antipsychotic drug development. Molecular dynamics studies indicate that DTG exhibits high stability and binding affinity for sigma-1 and dopamine D2 receptors, which may underlie its behavioral effects. Given the well-documented cataleptic properties of haloperidol, we compared and discussed both the molecular dynamics and previously reported behavioral effects of DTG in relation to haloperidol.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"859 ","pages":"Article 138267"},"PeriodicalIF":2.5,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144071604","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":"Tyrosol ameliorates depressive-like behavior and hippocampal damage in perimenopausal depression rats by inhibiting oxidative stress and thyroid dysfunction","authors":"Xiaolong Sun ,&nbsp;Meng Zhao ,&nbsp;Xu Wang ,&nbsp;Yinuo Sun ,&nbsp;Jing Li ,&nbsp;Yan Zhang ,&nbsp;Youzhi Zhang ,&nbsp;Xiaoling Feng","doi":"10.1016/j.neulet.2025.138266","DOIUrl":"10.1016/j.neulet.2025.138266","url":null,"abstract":"<div><div>Perimenopausal depression (PMD) is a common condition during the female perimenopausal period. Tyrosol represents a promising neuroprotective agent. This study aims to determine if tyrosol alleviate PMD progression. A rat model of PMD was established using bilateral ovariectomy and chronic unpredictable mild stress. Behavioral tests showed that tyrosol alleviated the depressive-like behavior in PMD rats. Tyrosol increased sucrose preference in SPT and residence time in the central region of OFT, and reduced immobility time in FST of PMD rats. Apoptosis of neurons in the hippocampus of PMD rats was inhibited by tyrosol treatment, as evidenced by an increase in the protein expression of Bcl-2 and a decrease in the expression of Bax and cleaved caspase-3 in hippocampal tissue. Tyrosol treatment effectively reduced thyroid-stimulating hormone levels and elevated the levels of free triiodothyronine and free thyroxine in the serum of PMD rats. The levels of ROS and MDA were decreased, and the levels of GPX and SOD were increased in the hippocampal tissue of PMD rats by tyrosol treatment. In addition, tyrosol treatment promoted the levels of brain-derived neurotrophic factor (BDNF) and monoamine neurotransmitters (5-HT, DA, and NA) in the hippocampal tissue. In summary, tyrosol might ameliorate depression-like behavior in PMD rats by inhibiting hippocampal oxidative stress and damage and promoting monoamine neurotransmitter release, and restoration of thyroid function may also be involved.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"859 ","pages":"Article 138266"},"PeriodicalIF":2.5,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094372","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":"Tripterygium-derived celastrol inhibits 5-HT3A receptors via key residue interactions: A comparative electrophysiological and docking study","authors":"Hye Duck Yeom ,&nbsp;Jihwon Yun ,&nbsp;Chaewon Seo ,&nbsp;Mee-Hyun Lee ,&nbsp;Gihyun Lee ,&nbsp;Junho H Lee","doi":"10.1016/j.neulet.2025.138265","DOIUrl":"10.1016/j.neulet.2025.138265","url":null,"abstract":"<div><div>This study examines the effects of three Tripterygium wilfordii compounds—celastrol, triptolide, and triptonide—on 5-HT3A receptors. Using two-electrode voltage-clamp recordings, we found all three compounds reversibly and concentration-dependently inhibited 5-HT-induced inward currents (I_5-HT), with celastrol showing the strongest inhibition (∼83 % at 100 µM) compared to triptolide (∼40 %) and triptonide (∼30 %) at 300 µM. Their voltage- and use-independent inhibition suggests they are not open-channel blockers. Further molecular docking and mutational analysis revealed celastrol binds to K127 and Y114, with mutations at these sites significantly reducing its inhibitory effect. Overall, celastrol, triptolide, and triptonide may suppress hyperactive gut signaling via 5-HT3A inhibition, with celastrol emerging as a promising therapeutic candidate.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"859 ","pages":"Article 138265"},"PeriodicalIF":2.5,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144071603","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":"Microinjection of brain-derived neurotrophic factor into the dorsal hippocampus alleviates cognitive dysfunction and increases hippocampal cell proliferation in olfactory bulbectomized mice","authors":"Jinichi Isono ,&nbsp;Osamu Nakagawasai ,&nbsp;Kohei Takahashi ,&nbsp;Wataru Nemoto ,&nbsp;Koichi Tan-No","doi":"10.1016/j.neulet.2025.138257","DOIUrl":"10.1016/j.neulet.2025.138257","url":null,"abstract":"<div><div>Patients with depression show cognitive dysfunction and experience decreased motivation, which interfere with their daily lives. However, whether brain-derived neurotrophic factor (BDNF) in the dorsal hippocampus is involved in depression-associated cognitive deficits is unclear. In this study, olfactory bulbectomized mice, used as a model of depression, showed cognitive dysfunction in the Y-maze and passive avoidance tests and reduction of cell proliferation in the hippocampal dentate gyrus. Microinjection of BDNF into the dorsal hippocampus alleviated the cognitive dysfunction induced by the olfactory bulbectomy and increased hippocampal cell proliferation. This study suggests that BDNF injection in the dorsal hippocampus modulates cognitive functions with cell proliferation in the hippocampal dentate gyrus, thus supporting the importance of hippocampal BDNF in cognitive impairment accompanying depression.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"859 ","pages":"Article 138257"},"PeriodicalIF":2.5,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144071605","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":"Ultra-high dilution medicines can modulate dopaminergic molecular targets and ΔFosB in the Nucleus accumbens preventing morphine reacquisition in rats","authors":"Murilo Barboza Fontoura ,&nbsp;Jessica Leandra Oliveira da Rosa ,&nbsp;Domenika Rubert Rossato ,&nbsp;Leana Eduarda Mezzomo de Souza ,&nbsp;Mustafa Munir Mustafa Dahleh ,&nbsp;Marina Prigol ,&nbsp;Gustavo Petri Guerra ,&nbsp;Hecson Jesser Segat ,&nbsp;Marilise Escobar Burger","doi":"10.1016/j.neulet.2025.138256","DOIUrl":"10.1016/j.neulet.2025.138256","url":null,"abstract":"<div><div>Addiction is a recurring disease that constitutes a significant public health issue, particularly evident in the global opioid crisis involving substances like morphine (MORPH). Reestablishing to opioid use poses a major obstacle to successful detoxification treatment, as many individuals return to drug use after withdrawal. Therefore, given that drug addiction involves emotional, social, and physical factors, there is a necessity to explore integrative medicine approaches, including ultra-high dilution medicines such as isotherapic (ISO) and organotherapic (ORG) treatments. This integrative approach holds promising potential in addressing drug addiction, as frequent reinstatement to addictive substances entail comprehensive symptoms. In our study following the MORPH conditioned place preference (CPP) paradigm, rats were treated with ISO or ORG for 14 days during MORPH-CPP extinction and subsequently challenged with the drug to assess MORPH-CPP reacquisition. The findings confirmed the hedonic effects of MORPH in the CPP, which also increased D1- and D3-R, DAT, and ΔFosB immunoreactivity in the <em>Nucleus accumbens</em> (NAc). Conversely, both ISO and ORG prevented MORPH-CPP reestablishing, whereas ORG treatment was associated with increased D2- and decreased D3-R levels. Both ORG and ISO increased DAT levels and decreased D1-R and ΔFosB, thus restoring the molecular neuromodulation induced by MORPH. To our knowledge, this study represents the first demonstration of the beneficial influence of ultra-high dilution medicines as a promising treatment for opioid use disorder. This finding is particularly relevant as these medicines are not associated with toxicity or undesirable side effects. Clinical studies are warranted to validate their efficacy in rehabilitation centers for drug use disorder.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"859 ","pages":"Article 138256"},"PeriodicalIF":2.5,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144071606","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":"Effects of repetition and estrous cycle on behavioral tests in female ICR mice","authors":"Michiyo Maruyama","doi":"10.1016/j.neulet.2025.138253","DOIUrl":"10.1016/j.neulet.2025.138253","url":null,"abstract":"<div><div>The open field test (OF) and elevated plus maze test (EPM) are widely used behavioral assessment methods for evaluating anxiety-like behaviors in rodents based on their spontaneous activity. These tests are commonly used to screen anxiolytic compounds. Repeated trials are often required to assess the efficacy of pharmacological treatments. Previous studies suggested that the number of experimental trials can influence various parameters in male animals. However, the knowledge of the effects of repeated trials on female mice is limited. Here, I report the effects of repeated testing on behavioral parameters in female ICR mice during the OF and EPM. The results showed that the number of trial repetitions influenced several behavioral parameters, consistent with previous findings in males. In contrast, the female-specific estrous cycle had a smaller effect. Overall, this study provides valuable insights for designing behavioral experiments involving female animals.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"859 ","pages":"Article 138253"},"PeriodicalIF":2.5,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143947614","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}