Molecular BrainPub Date : 2024-12-19DOI: 10.1186/s13041-024-01166-7
Qingzhi Wang, Xinjing Liu, Jing Yuan, Ting Yang, Lan Ding, Bo Song, Yuming Xu
{"title":"Nek6 regulates autophagy through the mTOR signaling pathway to alleviate cerebral ischemia-reperfusion injury.","authors":"Qingzhi Wang, Xinjing Liu, Jing Yuan, Ting Yang, Lan Ding, Bo Song, Yuming Xu","doi":"10.1186/s13041-024-01166-7","DOIUrl":"10.1186/s13041-024-01166-7","url":null,"abstract":"<p><strong>Objective: </strong>Cerebral ischemia-reperfusion injury (CIRI) is a major obstacle to neurological recovery after clinical treatment of ischemic stroke. The aim of this study was to investigate the molecular mechanism of Nek6 alleviating CIRI through autophagy after cerebral ischemia.</p><p><strong>Materials and methods: </strong>A mouse model of CIRI was constructed by middle cerebral artery occlusion (MCAO). TUNEL staining was used to observe the apoptosis of neuronal cells. The oxygen glucose deprivation/reoxygenation (OGD/R) model was established by hypoxia and reoxygenation. The cell apoptosis and activity was detected. Western blot was performed to detect the expression of autophagy-related proteins, protein kinase B (Akt)/mammalian target of rapamycin (mTOR) and adenosine 5'-monophosphate-activated protein kinase (AMPK)/mTOR signaling pathway-related proteins. Cellular autophagy flux was observed by fluorometric method. NIMA-related kinase 6 (Nek6) mRNA stability was detected by actinomycin D treatment. Methylation RNA immunoprecipitation technique was used to detect Nek6 methylation level.</p><p><strong>Results: </strong>Nek6 expression was increased in both MCAO and OGD/R models. Overexpression of Nek6 in OGD/R inhibited apoptosis, decreased LC3II and Beclin-1 expression, increased p62 expression, and occurred lysosome dysfunction. Interference with Nek6 has opposite results. Nek6 overexpression promoted p-Akt and p-mTOR protein expressions, inhibited p-AMPK and p-UNC-51-like kinase 1 protein expressions and cell apoptosis, while LY294002, Rapamycin or RSVA405 treatment reversed this effect. Abnormal methyltransferase·like protein 3 (METTL3) expression in CIRI enhanced m6A modification and promoted Nek6 expression level.</p><p><strong>Conclusion: </strong>This study confirmed that Nek6 regulates autophagy and alleviates CIRI through the mTOR signaling pathway, which provides a novel therapeutic strategy for patients with ischemic stroke in the future.</p>","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":"17 1","pages":"96"},"PeriodicalIF":3.3,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11658364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864371","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}
Molecular BrainPub Date : 2024-12-18DOI: 10.1186/s13041-024-01168-5
Evgenii Gerasimov, Ekaterina Pchitskaya, Olga Vlasova, Ilya Bezprozvanny
{"title":"Dynamic changes in the hippocampal neuronal circuits activity following acute stress revealed by miniature fluorescence microscopy imaging.","authors":"Evgenii Gerasimov, Ekaterina Pchitskaya, Olga Vlasova, Ilya Bezprozvanny","doi":"10.1186/s13041-024-01168-5","DOIUrl":"10.1186/s13041-024-01168-5","url":null,"abstract":"<p><p>Coordinated activity of neuronal ensembles is a basis for information processing in the brain. Recent development of miniscope imaging technology enabled recordings of neuronal circuits activity in vivo in freely behaving animals. Acute stress is believed to affect various hippocampal functions, especially memory. In the current study, we utilized miniscope imaging to investigate the hippocampal neuronal circuits properties in a mouse as function of time and immediately in response to an acute stress, induced by passive restraint, 3 h and 10 days after. Comprehensive quantitative analysis of network activity changes at the neuronal ensembles level revealed highly stable neuronal activity parameters, which exhibited a rapid and robust shift in response to acute stress stimulation. This shift was accompanied by the restructuring of the pairwise-correlated neuronal pairs. Remarkably, we discovered that ensembles activity characteristics returned to the initial state following recovery period, demonstrating hippocampal homeostatic stability at the neuronal circuits level. Obtained results provide an evidence about hippocampal neuronal ensembles activity in response to acute stress over time.</p>","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":"17 1","pages":"92"},"PeriodicalIF":3.3,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11653891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854861","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}
Molecular BrainPub Date : 2024-12-18DOI: 10.1186/s13041-024-01169-4
Ali Azargoonjahromi
{"title":"Serotonin enhances neurogenesis biomarkers, hippocampal volumes, and cognitive functions in Alzheimer's disease.","authors":"Ali Azargoonjahromi","doi":"10.1186/s13041-024-01169-4","DOIUrl":"10.1186/s13041-024-01169-4","url":null,"abstract":"<p><p>Research on serotonin reveals a lack of consensus regarding its role in brain volume, especially concerning biomarkers linked to neurogenesis and neuroplasticity, such as ciliary neurotrophic factor (CNTF), fibroblast growth factor 4 (FGF-4), bone morphogenetic protein 6 (BMP-6), and matrix metalloproteinase-1 (MMP-1) in Alzheimer's disease (AD). This study aimed to investigate the influence of serotonin on brain structure and hippocampal volumes in relation to cognitive functions in AD, as well as its link with biomarkers like CNTF, FGF-4, BMP-6, and MMP-1. Data from 133 ADNI participants with AD included cognitive assessments (CDR-SB), serotonin measurements (Biocrates AbsoluteIDQ p180 kit, UPLC-MS/MS), and neurotrophic factors quantified via multiplex proteomics. Gray matter volume changes were analyzed using Voxel-Based Morphometry (VBM) with MRI. Statistical analyses employed Pearson correlation, bootstrap methods, and FDR-adjusted p-values (< 0.05 or < 0.01) via the Benjamini-Hochberg procedure, alongside nonparametric methods. The analysis found a positive correlation between serotonin levels and total brain (r = 0.229, p = 0.023) and hippocampal volumes (right: r = 0.186, p = 0.032; left: r = 0.210, p = 0.023), even after FDR adjustment. Higher serotonin levels were linked to better cognitive function (negative correlation with CDR-SB, r = -0.230, p = 0.024). Notably, serotonin levels were positively correlated with BMP-6 (r = 0.173, p = 0.047), CNTF (r = 0.216, p = 0.013), FGF-4 (r = 0.176, p = 0.043), and MMP-1 (r = 0.202, p = 0.019), suggesting a link between serotonin and neurogenesis and neuroplasticity. However, after adjusting for multiple comparisons and controlling for confounding factors such as age, gender, education, and APOE genotypes (APOE3 and APOE4), none of the correlations of biomarkers remained statistically significant. In conclusion, increased serotonin levels are associated with improved cognitive function and increased brain volume. However, associations with CNTF, FGF-4, BMP-6, and MMP-1 were not statistically significant after adjustments, highlighting the complexity of serotonin's role in AD and the need for further research.</p>","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":"17 1","pages":"93"},"PeriodicalIF":3.3,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11654273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854908","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}
Molecular BrainPub Date : 2024-12-18DOI: 10.1186/s13041-024-01158-7
Amber J Zimmerman, Antonio Serrano-Rodriguez, Melody Sun, Sandy J Wilson, David N Linsenbardt, Jonathan L Brigman, Jason P Weick
{"title":"Knockout of AMPA receptor binding protein Neuron-specific gene 2 (NSG2) enhances associative learning and cognitive flexibility.","authors":"Amber J Zimmerman, Antonio Serrano-Rodriguez, Melody Sun, Sandy J Wilson, David N Linsenbardt, Jonathan L Brigman, Jason P Weick","doi":"10.1186/s13041-024-01158-7","DOIUrl":"10.1186/s13041-024-01158-7","url":null,"abstract":"<p><p>The vast majority of gene mutations and/or gene knockouts result in either no observable changes, or significant deficits in molecular, cellular, or organismal function. However, in a small number of cases, mutant animal models display enhancements in specific behaviors such as learning and memory. To date, most gene deletions shown to enhance cognitive ability generally affect a limited number of pathways such as NMDA receptor- and translation-dependent plasticity, or GABA receptor- and potassium channel-mediated inhibition. While endolysosomal trafficking of AMPA receptors is a critical mediator of synaptic plasticity, mutations in genes that affect AMPAR trafficking either have no effect or are deleterious for synaptic plasticity, learning and memory. NSG2 is one of the three-member family of Neuron-specific genes (NSG1-3), which have been shown to regulate endolysosomal trafficking of a number of proteins critical for neuronal function, including AMPAR subunits (GluA1-2). Based on these findings and the largely universal expression throughout mammalian brain, we predicted that genetic knockout of NSG2 would result in significant impairments across multiple behavioral modalities including motor, affective, and learning/memory paradigms. However, in the current study we show that loss of NSG2 had highly selective effects on associative learning and memory, leaving motor and affective behaviors intact. For instance, NSG2 KO animals performed equivalent to wild-type C57Bl/6n mice on rotarod and Catwalk motor tasks, and did not display alterations in anxiety-like behavior on open field and elevated zero maze tasks. However, NSG2 KO animals demonstrated enhanced recall in the Morris water maze, accelerated reversal learning in a touch-screen task, and accelerated acquisition and enhanced recall on a Trace Fear Conditioning task. Together, these data point to a specific involvement of NSG2 on multiple types of associative learning, and expand the repertoire of pathways that can be targeted for cognitive enhancement.</p>","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":"17 1","pages":"95"},"PeriodicalIF":3.3,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11654403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854878","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}
Molecular BrainPub Date : 2024-12-18DOI: 10.1186/s13041-024-01167-6
Alan Jung Park
{"title":"Novelty triggers time-dependent theta oscillatory dynamics in cortical-hippocampal-midbrain circuitry.","authors":"Alan Jung Park","doi":"10.1186/s13041-024-01167-6","DOIUrl":"10.1186/s13041-024-01167-6","url":null,"abstract":"<p><p>Rapid adaptation to novel environments is crucial for survival, and this ability is impaired in many neuropsychiatric disorders. Understanding neural adaptation to novelty exposure therefore has therapeutic implications. Here, I found that novelty induces time-dependent theta (4-12Hz) oscillatory dynamics in brain circuits including the medial prefrontal cortex (mPFC), ventral hippocampus (vHPC), and ventral tegmental area (VTA), but not dorsal hippocampus (dHPC), as mice adapt to a novel environment. Local field potential (LFP) recordings were performed while mice were freely behaving in a novel or a familiar arena for 10 min. Initially, mice exhibited increased exploratory behavior upon exposure to novelty, which gradually decreased to levels observed in mice exposed to the familiar arena. Over the same time course, the mPFC, vHPC, and VTA displayed progressively increasing theta power through novelty exposure. Additionally, theta coherence and theta phase synchrony measures demonstrated that novelty weakened the connectivity between these areas, which then gradually strengthened to the level observed in the familiar group. Conversely, mice exposed to the familiar arena showed steady and consistent behavior as well as theta dynamics in all areas. Treatment with a dopamine D1-receptor (D1R) antagonist in the vHPC disrupted neurophysiological adaptation to novelty specifically in the vHPC-mPFC and vHPC-VTA circuits, without affecting behavior. Thus, novelty induces distinct theta dynamics that are not readily dictated by behavior in the mPFC, vHPC, and VTA circuits, a process mediated by D1Rs in the vHPC. The observed time-dependent circuit dynamics in the key learning and memory circuit would provide new insights for treating neuropsychiatric disorders that often show impaired novelty processing.</p>","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":"17 1","pages":"94"},"PeriodicalIF":3.3,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11654259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854883","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}
Molecular BrainPub Date : 2024-11-29DOI: 10.1186/s13041-024-01163-w
Daisuke Miyamoto, Mahmoud Abdelmouti Mahmoud
{"title":"Post-conditioning sleep deprivation facilitates delay and trace fear memory extinction.","authors":"Daisuke Miyamoto, Mahmoud Abdelmouti Mahmoud","doi":"10.1186/s13041-024-01163-w","DOIUrl":"10.1186/s13041-024-01163-w","url":null,"abstract":"<p><p>Trace and delay auditory fear conditioning involve different memory association strategies based on working memory involvement; however, their differences in long-term processing through sleep and extinction training remain unclear. While females often exhibit more persistent fear, complicating psychiatric treatment, most studies have primarily focused on how sleep affects initial recall in male mice. We investigated the three-way interaction between tests (trace vs. delay), sleep states, and sex during initial recall, extinction, and post-extinction remote recall. A six-hour post-conditioning sleep deprivation (SD) did not affect freezing behavior during the following day's extinction training of delay fear memory. However, during post-extinction remote recall of delay fear memory, SD prevented spontaneous recovery in males and reduced persistent freezing in females. In contrast, SD rapidly facilitated extinction of trace fear memory. In summary, SD enhances extinction both in the short-term and long-term, depending on the conditioning protocol. These findings highlight the importance of long-term assessments to explore interactions among emotional memory, sleep, and sex differences, with implications for individualized mechanisms underlying post-traumatic stress disorder (PTSD) and its treatments.</p>","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":"17 1","pages":"90"},"PeriodicalIF":3.3,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11605955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755487","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}
Molecular BrainPub Date : 2024-11-29DOI: 10.1186/s13041-024-01164-9
Jianbang Lin, Jing Liu, Qi Zhang, Taian Liu, Zexuan Hong, Yi Lu, Cheng Zhong, Zhonghua Lu, Yuantao Li, Yu Hu
{"title":"Chemogenetic silencing of the subiculum blocks acute chronic temporal lobe epilepsy.","authors":"Jianbang Lin, Jing Liu, Qi Zhang, Taian Liu, Zexuan Hong, Yi Lu, Cheng Zhong, Zhonghua Lu, Yuantao Li, Yu Hu","doi":"10.1186/s13041-024-01164-9","DOIUrl":"10.1186/s13041-024-01164-9","url":null,"abstract":"<p><p>Temporal lobe epilepsy (TLE) is the most common form of medically-intractable epilepsy. Subicular hyperexcitability is frequently observed with TLE, presumably caused by impaired inhibition of local excitatory neurons. Here, we evaluated the effectiveness of silencing subicular pyramidal neurons to treat a rodent model of TLE. First, we generated a chronic TLE mouse model via initial intrahippocampal kainic acid (IHKA) injection. In the chronic state after first IHKA injection, behavioral seizures and histological abnormalities were reliably observed. We then injected an adeno-associated viral (AAV) vector carrying an inhibitory chemogenetic element, hM4D<sub>i</sub>, directly into the subiculum. Eight weeks after the first IHKA injection, acute seizures were induced by giving a second dose of kainic acid (KA), which mimicked generalized tonic-clonic seizures. Herein, precise control over generalized tonic-clonic seizure onset was achieved via this two-step process. We found that chemogenetic suppression of subicular pyramidal neurons had a robust anti-epileptogenesis effect in this acute-chronic model of TLE. These data confirm a crucial role of the subiculum in the propagation of hippocampal seizures and highlight the potential for using subicular chemogenetic manipulation to treat generalized tonic-clonic seizures.</p>","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":"17 1","pages":"91"},"PeriodicalIF":3.3,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11606012/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755480","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}
Molecular BrainPub Date : 2024-11-28DOI: 10.1186/s13041-024-01161-y
Min-Ki Kim, Sung-Phil Kim, Jeong-Woo Sohn
{"title":"Synthetic data-driven overlapped neural spikes sorting: decomposing hidden spikes from overlapping spikes.","authors":"Min-Ki Kim, Sung-Phil Kim, Jeong-Woo Sohn","doi":"10.1186/s13041-024-01161-y","DOIUrl":"10.1186/s13041-024-01161-y","url":null,"abstract":"<p><p>Sorting spikes from extracellular recordings, obtained by sensing neuronal activity around an electrode tip, is essential for unravelling the complexities of neural coding and its implications across diverse neuroscientific disciplines. However, the presence of overlapping spikes, originating from neurons firing simultaneously or within a short delay, has been overlooked because of the difficulty in identifying individual neurons due to the lack of ground truth. In this study, we propose a method to identify overlapping spikes in extracellular recordings and to recover hidden spikes by decomposing them. We initially estimate spike waveform templates through a series of steps, including discriminative subspace learning and the isolation forest algorithm. By leveraging these estimated templates, we generate synthetic spikes and train a classifier using their feature components to identify overlapping spikes from observed spike data. The identified overlapping spikes are then decomposed into individual hidden spikes using a particle swarm optimization. Results from the testing of the proposed approach, using the simulation dataset we generated, demonstrated that employing synthetic spikes in the overlapping spike classifier accurately identifies overlapping spikes among the detected ones (the maximum F1 score of 0.88). Additionally, the approach can infer the synchronization between hidden spikes by decomposing the overlapped spikes and reallocating them into distinct clusters. This study advances spike sorting by accurately identifying overlapping spikes, providing a more precise tool for neural activity analysis.</p>","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":"17 1","pages":"89"},"PeriodicalIF":3.3,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11606139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751214","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":"Histamine H<sub>3</sub> receptor inverse agonists/antagonists influence intra-regional cortical activity and inter-regional synchronization during resting state: an exploratory cortex-wide imaging study in mice.","authors":"Sentaro Kaita, Yoshikazu Morishita, Kenta Kobayashi, Hiroshi Nomura","doi":"10.1186/s13041-024-01165-8","DOIUrl":"10.1186/s13041-024-01165-8","url":null,"abstract":"<p><p>The histaminergic system plays a key role in modulating learning and memory, wakefulness, and energy balance. Histamine H<sub>3</sub> receptors constitutively inhibit the synthesis and release of histamine and other neurotransmitters. Therefore, H<sub>3</sub> receptor inverse agonists/antagonists increase the synthesis and release of these neurotransmitters, enhancing cognitive functions, including memory consolidation and retrieval. Spontaneous neural activity across the cerebral cortex is essential for cognitive function, including memory consolidation. Abnormal spontaneous activity has, in fact, been associated with cognitive dysfunctions and psychiatric disorders. Given the cognitive improvement achieved with the use of H<sub>3</sub> receptor inverse agonists/antagonists, we examined the effects of two inverse agonists/antagonists - thioperamide and pitolisant - on spontaneous cortical activity, using in vivo wide-field Ca<sup>2+</sup> imaging. Changes in cortical activity, across multiple cortical regions and in inter-regional connectivity, from pre- to post-administration were evaluated using a linear support vector machine decoder. Thioperamide and pitolisant both modified the amplitude distribution of calcium events across multiple cortical regions, including a reduction in the frequency of low-amplitude calcium events in the somatosensory cortex. Graph theory analysis revealed increases in centrality measures in the somatosensory cortex with the use of both thioperamide and pitolisant, indicative of their importance in the organization of cortical networks. These findings indicate that H<sub>3</sub> receptor inverse agonists/antagonists influence intra-regional cortical activity and inter-regional synchronization of activity in the cerebral cortex during the resting state.</p>","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":"17 1","pages":"88"},"PeriodicalIF":3.3,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11603655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739705","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}
Molecular BrainPub Date : 2024-11-27DOI: 10.1186/s13041-024-01162-x
Tae-Yong Choi, Jeongseop Kim, Ja Wook Koo
{"title":"Transcutaneous auricular vagus nerve stimulation in anesthetized mice induces antidepressant effects by activating dopaminergic neurons in the ventral tegmental area.","authors":"Tae-Yong Choi, Jeongseop Kim, Ja Wook Koo","doi":"10.1186/s13041-024-01162-x","DOIUrl":"10.1186/s13041-024-01162-x","url":null,"abstract":"<p><p>Depression, a prevalent neuropsychiatric disorder, involves the dysregulation of neurotransmitters such as dopamine (DA). The restoration of DA balance is a pivotal therapeutic target for this condition. Recent studies have indicated that both antidepressant medications and non-pharmacological treatments, such as transcutaneous auricular vagus nerve stimulation (taVNS), can promote recovery from depressive symptoms. Despite the promise of taVNS as a non-invasive depression therapy, its precise mechanism remains unclear. We hypothesized that taVNS exerts antidepressant effects by modulating the DAergic system. To investigate this, we conducted experiments demonstrating that taVNS in anesthetized mice reduced depressive-like behaviors. However, this effect was abolished when DA neurons in the ventral tegmental area (VTA<sup>DA</sup>) were inhibited. Additionally, taVNS in anesthetized mice enhanced VTA<sup>DA</sup> activity, providing further evidence to support its antidepressant effects. Overall, our findings suggest that taVNS alleviates depression by augmenting VTA<sup>DA</sup> activity, thereby contributing to a more comprehensive understanding of its therapeutic mechanisms.</p>","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":"17 1","pages":"86"},"PeriodicalIF":3.3,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11600629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739914","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}