Neuroscience最新文献

{"title":"S-(+)-mecamylamine increases the firing rate of serotonin neurons and diminishes depressive-like behaviors in an animal model of stress","authors":"A. Mondragón-García ,&nbsp;E. Ramírez-Sánchez ,&nbsp;D. Francia-Ramírez ,&nbsp;O. Hernández-González ,&nbsp;Y. Rojano-Posada ,&nbsp;S. Ortega-Tinoco ,&nbsp;J. Garduño ,&nbsp;L. Verdugo-Díaz ,&nbsp;S. Hernández-López","doi":"10.1016/j.neuroscience.2024.10.043","DOIUrl":"10.1016/j.neuroscience.2024.10.043","url":null,"abstract":"<div><div>Mecamylamine, a noncompetitive blocker of nicotinic acetylcholine receptors (nAChRs), is the racemic mixture of two stereoisomers: S-(+)-mecamylamine (S-mec) and R-(−)-mecamylamine (R-mec), with distinct interactions with α4β2 nAChRs. It has been shown that mecamylamine increases glutamate release and excites serotonergic (5-HT) neurons in the dorsal raphe nucleus (DRN). In this study, we separately evaluated the effects of S-mec and R-mec on 5-HT neuron excitability. S-mec (3 μM) increased firing frequency by 40 %, while R-mec (3 μM) raised it by only 22 %. S-mec acts as a positive allosteric modulator on high-sensitivity (HS) α4β2 nAChRs at glutamate terminals, enhancing spontaneous excitatory postsynaptic currents (sEPSCs) in 5-HT neurons. Conversely, R-mec decreased sEPSCs by blocking HS α4β2 nAChRs and reduced GABA-mediated inhibitory currents (sIPSCs) by blocking α7 nAChRs at GABAergic terminals. These mechanisms make S-mec more effective than R-mec in enhancing 5-HT neuron firing. Moreover, combining S-mec with TC-2559, a selective agonist of HS α4β2 nAChRs, increased firing frequency by 65 %, exceeding the effect of S-mec alone. To validate these findings, we evaluated the antidepressant effects of S-mec (1 mg/kg) combined with TC-2559 or RJR-2403, another α4β2 nAChR agonist. This combination successfully reduced depression-like behaviors, suggesting a potential treatment strategy for patients resistant to conventional antidepressants.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"562 ","pages":"Pages 75-89"},"PeriodicalIF":2.9,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nitric oxide synthase system in the brain development of neonatal hypothyroid rats.","authors":"Juan Carlos López-Ramos, Esther Martínez-Lara, Julia Serrano, Patricia Fernández, Gloria G Parras, Antonio Ruiz-Marcos, José Rodrigo","doi":"10.1016/j.neuroscience.2024.10.040","DOIUrl":"https://doi.org/10.1016/j.neuroscience.2024.10.040","url":null,"abstract":"<p><p>Thyroid hormones play an important morphogenetic role during the fetal and neonatal periods and regulate numerous metabolic processes. In the central nervous system, they control myelination and overall brain development, regional gene expression, and regulation of oxygen consumption. Their deficiency in the fetal and neonatal periods causes severe mental retardation, due to lack of thyroid function, or to iodine deficiency. At the same time, nitric oxide is an atypical neurotransmitter that also has special relevance in neuronal development and plasticity and functions as a vasodilator, regulating cerebral blood flow. Although under physiological conditions it functions as a neuroprotector, in excess it can be neurotoxic. We have studied, by immunocytochemical and Western blot techniques, the evolution of the expression of neuronal and inducible isoforms of the enzyme nitric oxide synthase, and of nitrotyrosine as a marker of protein nitration produced by the presence of nitric oxide, during the early stages of postnatal brain development. We induced hypothyroidism by administering mercaptomethylimidazole to pregnant mothers, from the seventh day of gestation until the sacrifice of the offspring. The results show a delay in the evolution of the expression of the two isoforms of the enzyme nitric oxide synthase in hypothyroid animals, followed by an anomalous overexpression in later stages. Finally, the expression of nitrotyrosine follows an evolution that is synchronized with that shown by both isoenzymes in control and hypothyroid animals.</p>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of tenofovir by probenecid: Impact on drug, interleukin-1β, and dopamine concentration in the prefrontal cortex and cerebellum","authors":"Simangele NE Shabalala,&nbsp;M. Luvuno,&nbsp;M.V. Mabandla","doi":"10.1016/j.neuroscience.2024.10.031","DOIUrl":"10.1016/j.neuroscience.2024.10.031","url":null,"abstract":"<div><div>The blood–brain barrier’s limited permeability to tenofovir restricts its ability to clear HIV from the brain. Probenecid acting as an adjuvant increases tenofovir concentrations in plasma and the kidneys thereby enhancing its therapeutic effect. However, the probenecid effect on brain tenofovir concentration and possible adverse effects remains poorly understood. We investigated the effect of probenecid co-administered tenofovir on tenofovir brain concentration, interleukin-1β (IL-1β) and dopamine concentration in the prefrontal cortex (PFC) and the cerebellum. Ninety-six male BALB/c mice were divided into four groups viz: a control group, Tenofovir disoproxil fumarate (TDF) treated, probenecid treated, and TDF + probenecid treated. We orally administered a single dose of TDF (5 mg/kg), and probenecid (8.3 mg/kg), and sacrificed six mice per group after 1 h, 4 h, and 6 h post-treatment to collect plasma, PFC, and cerebellar tissue. Co-administered tenofovir increased tenofovir concentration, peaking at 6 h with the cerebellum having the highest concentration. This suggests that probenecid enhanced the entry of tenofovir into the brain. Tenofovir alone increased IL-1β concentration at all intervals post-administration, while probenecid alone had no impact on IL-1β concentration. Co-administered tenofovir also increased IL-1β concentration. Probenecid’s limited impact on IL-1β concentration following co-administration suggests that its anti-inflammatory properties may require more than 6 h to have an effect. Furthermore, neither tenofovir nor probenecid affected dopamine concentration. In conclusion, probenecid enhances the concentration and retention of tenofovir in the brain, making it a possible pharmacokinetic enhancer. However, its anti-inflammatory effects may require a longer duration to fully manifest.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"562 ","pages":"Pages 209-216"},"PeriodicalIF":2.9,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hippocampal fimbria atrophy and its mediating effect between cerebral small vessel disease and cognitive impairment","authors":"Na Wang ,&nbsp;Jing Li ,&nbsp;Xinyue Zhang ,&nbsp;Yian Gao ,&nbsp;Chaofan Sui ,&nbsp;Nan Zhang ,&nbsp;Yena Che ,&nbsp;Changhu Liang ,&nbsp;Lingfei Guo ,&nbsp;Meng Li","doi":"10.1016/j.neuroscience.2024.10.039","DOIUrl":"10.1016/j.neuroscience.2024.10.039","url":null,"abstract":"<div><div>We aimed to investigate the relationship between the volume reduction in hippocampal (HP) subregions and cognitive impairment in patients with cerebral small vessel disease (CSVD). Clinical, cognitive, and magnetic resonance imaging data were obtained for 315 participants. The CSVD group included 146 participants with a total CSVD score of 1–4. 169 participants with a total CSVD score of zero were used as control group (CSVD-0). The volume differences of 19 HP subregions between CSVD and CSVD–0 groups were analyzed, and we investigated the hazard factors that might cause subregional volume reduction in HP. Mediation analysis was performed to detect the relationship among HP subregional volumes, CSVD burden, and cognitive function. In our results, significant differences can be found in the volumes of CA4 body, presubiculum–head, presubiculum–body, subiculum–body, GC–ML–DG–head, GC–ML–DG–body, fimbria, and HP tail between CSVD group and control group. Regression analysis showed that fimbria was the most impacted HP subregion by CSVD. And mediation analysis revealed fimbria volume was a mediator variable between total CSVD score and MoCA/SCWT score. These results suggest that the volumes of HP subregions, especially the fimbria, may be effective potential biomarkers for early detecting cognitive impairment in CSVD.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"562 ","pages":"Pages 54-62"},"PeriodicalIF":2.9,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exercise preconditioning mitigates Ischemia-Reperfusion injury in rats by enhancing mitochondrial respiration","authors":"Runyu Liang ,&nbsp;Xinlei Hou ,&nbsp;Daguo Zhou ,&nbsp;Luwen Zhu ,&nbsp;Lili Teng ,&nbsp;Wenjing Song ,&nbsp;Qiang Tang","doi":"10.1016/j.neuroscience.2024.10.045","DOIUrl":"10.1016/j.neuroscience.2024.10.045","url":null,"abstract":"<div><div>Cerebral ischemia and subsequent reperfusion damage are prevalent in clinical practice, linked to numerous neurodegenerative diseases. Cerebral ischemia deprives brain tissue of essential oxygen and nutrients, disrupting energy metabolism and causing cellular dysfunction. Although reperfusion theoretically aids recovery, it instead initiates complex injury responses such as oxidative stress, apoptosis, and inflammation, worsening brain damage. Recent research suggests that enhancing neuronal energy status by modulating energy metabolism pathways can effectively counter these effects. For instance, boosting mitochondrial function, improving energy provision, and decreasing harmful metabolites can mitigate oxidative stress and cellular injury. This study investigated the protective effects of exercise preconditioning against ischemia–reperfusion injury in rats. It was observed that exercise enhances energy levels and mitochondrial respiration by upregulating the expression of COX4 and NAMPT proteins and activating AMPK and mitochondrial complex V. This process facilitates metabolic reprogramming characterized by the promotion of oxidative phosphorylation (OXPHOS) and the pentose phosphate pathway (PPP), alongside a reduction in glycolysis. Such reprogramming reduces harmful metabolites, mitigating apoptosis and oxidative stress, and is a key factor in alleviating acute ischemic hypoxia-induced brain damage. These findings introduce a novel therapeutic approach for ischemic brain reperfusion injury, underscoring the crucial role of ATP production and metabolic regulation in neuroprotection.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"562 ","pages":"Pages 64-74"},"PeriodicalIF":2.9,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alcohol augmentation of acrolein-mediated brain injury in blast-induced TBI","authors":"","doi":"10.1016/j.neuroscience.2024.10.036","DOIUrl":"10.1016/j.neuroscience.2024.10.036","url":null,"abstract":"","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"562 ","pages":"Pages 252-253"},"PeriodicalIF":2.9,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EMG and SSVEP-based bimodal estimation of elbow angle trajectory","authors":"Fatemeh Davarinia,&nbsp;Ali Maleki","doi":"10.1016/j.neuroscience.2024.10.030","DOIUrl":"10.1016/j.neuroscience.2024.10.030","url":null,"abstract":"<div><div>Detecting intentions and estimating movement trajectories in a human–machine interface (HMI) using electromyogram (EMG) signals is particularly challenging, especially for individuals with movement impairments. Therefore, incorporating additional information from other biological sources, potential discrete information in the movement, and the EMG signal can be practical. This study combined EMG and target information to enhance estimation performance during reaching movements. EMG activity of the shoulder and arm muscles, elbow angle, and the electroencephalogram signals of ten healthy subjects were recorded while they reached blinking targets. The reaching target was recognized by steady-state visual evoked potential (SSVEP). The selected target’s final angle and EMG were then mapped to the elbow angle trajectory. The proposed bimodal structure, which integrates EMG and final elbow angle information, outperformed the EMG-based decoder. Even under conditions of higher fatigue, the proposed structure provided better performance than the EMG decoder. Including additional information about the recognized reaching target in the trajectory model improved the estimation of the reaching profile. Consequently, this study’s findings suggest that bimodal decoders are highly beneficial for enhancing assistive robotic devices and prostheses, especially for real-time upper limb rehabilitation.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"562 ","pages":"Pages 1-9"},"PeriodicalIF":2.9,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thalamus and its functional connections with cortical regions contribute to complexity-dependent cognitive reasoning","authors":"Yanqing Wang","doi":"10.1016/j.neuroscience.2024.10.034","DOIUrl":"10.1016/j.neuroscience.2024.10.034","url":null,"abstract":"<div><div>The thalamus is crucial for supporting various cognitive behaviors due to its extensive connectivity with multiple cortical regions. However, the role of the thalamus and its functional connections with cortical regions in cognitive reasoning remains unclear, since previous research has mainly focused on cortical regions when studying the neural mechanisms underlying cognitive reasoning. To fill this knowledge gap, we utilized 7 T functional magnetic resonance imaging (fMRI) to study the activation patterns of the thalamus and its functional connections with cortical regions during cognitive reasoning task, while also examining how the complexity of reasoning tasks affects thalamic activation and functional connections with cortical regions. Our findings showed that cognitive reasoning processes are related to increased activation of the thalamus and its functional connections with a specific set of cortical regions, consisting of dorsolateral prefrontal cortex, inferior frontal sulcus, intraparietal sulcus, anterior cingulate cortex/presupplementary motor area, precuneus, and ventral medial prefrontal cortex. Moreover, the increase in relational complexity of the reasoning tasks led to a corresponding increase in thalamic activation and functional connectivity with cortical regions. Given the complex thalamus structure, including multiple distinct nuclei exhibiting specific functional connections with particular cortical regions, we used an atlas defined thalamic subdivisions based on its structural connectivity with different cortical regions. Our findings indicated that these different thalamic subregions not only exhibited distinct connectivity patterns with specific cortical regions during performance of cognitive reasoning, but also showed distinct connectivity patterns varied with task complexity. Overall, our study presents evidence of the thalamus’s role and its connections with cortical regions in supporting increasingly complex cognitive reasoning behavior, illuminating its contribution to higher-order cognitive functions, such as reasoning.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"562 ","pages":"Pages 125-134"},"PeriodicalIF":2.9,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effects of chronic desipramine treatment on neurotrophin-3 in the brain of mice with selective depletion of CREB and CREM in noradrenergic neurons","authors":"Katarzyna Rafa-Zabłocka,&nbsp;Irena Nalepa,&nbsp;Grzegorz Kreiner","doi":"10.1016/j.neuroscience.2024.10.020","DOIUrl":"10.1016/j.neuroscience.2024.10.020","url":null,"abstract":"<div><div>The disturbances in neurotrophic support are thought to be one of the main causes of depression, which depend not only on the neurotrophins themselves but also on the molecules regulating their synthesis and effector functions. One such molecule is cAMP responsive element binding protein (CREB), which role in depression and antidepressant drugs mechanism of action has been extensively studied. However, CREB’s effects vary depending on brain structure, necessitating specific transgenic models for studying its function. Moreover, deletion of CREB enhances cAMP response element modulator (CREM) expression, suspected to compensate for CREB in its absence.</div><div>Previously, mice lacking CREB in noradrenergic neurons and CREM (Creb1^DbhCreCrem-/-) showed to be insensitive to acute desipramine, whereas mice lacking only CREB (Creb1^DbhCre) showed similar effects as wild type animals (w/t). As neurotrophic changes require chronic antidepressant treatment, in current study mice (w/t, Creb1^DbhCre and Creb1^DbhCreCrem-/-; both males and females) were given desipramine for 21 days, to assess the effects of the drug on CREB, neurotrophins and their receptors in the hippocampus and prefrontal cortex.</div><div>Interestingly, desipramine had no effect on CREB in neither of studied groups. However, both male and female mice lacking CREB and CREM displayed alterations in neurotrophin-3 (NTF3) expression or protein levels, modulated by desipramine. These findings suggest NTF3 is connected with inhibited response to acute and probably chronic desipramine administration in Creb1^DbhCreCrem–/– mice, although in w/t chronic desipramine had no effect on NTF3. Nevertheless, our findings give insight into the role of non-BDNF neurotrophins in the mechanism of antidepressant drugs.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"562 ","pages":"Pages 190-197"},"PeriodicalIF":2.9,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The presence of drum and bass modulates responses in the auditory dorsal pathway and mirror-related regions to pop songs","authors":"Chia-Wei Li ,&nbsp;Chen-Gia Tsai","doi":"10.1016/j.neuroscience.2024.10.024","DOIUrl":"10.1016/j.neuroscience.2024.10.024","url":null,"abstract":"<div><div>In pop music, drum and bass components are crucial for generating the desire to move one’s body, primarily due to their role in delivering salient metrical cues. This study explored how the presence of drum and bass influences neural responses to unfamiliar pop songs. Using AI-based algorithms, we isolated the drum and bass components from the musical excerpts, creating two additional versions: one that included only the drum and bass (excluding vocals and other instruments), and another that excluded the drum and bass (consisting solely of vocals and other instruments). Twenty-five participants were subjected to fMRI scans while listening to these musical stimuli. Analysis of fMRI data indicated that the removal of drum and bass led to increased activity in the auditory dorsal pathway, suggesting that the absence of these metrical cues demands greater cognitive effort to process the beats. In contrast, the version featuring only drum and bass elicited stronger activation in frontal regions associated with mirror properties, including the right ventral premotor cortex (extending into the inferior frontal gyrus) and left dorsolateral prefrontal cortex, compared to the original version. Overall, this study contributed insights into the foundational role of drum and bass in imparting metrical salience to pop songs, enriching our understanding of listeners’ sensorimotor processing of musical genres that prominently feature these two elements.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"562 ","pages":"Pages 24-32"},"PeriodicalIF":2.9,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}