Experimental Neurobiology最新文献

Focused Ultrasound as a Plasma Protein Binding-targeted Strategy to Enhance Brain Uptake of Donepezil. 聚焦超声作为血浆蛋白结合靶向策略增强大脑对多奈哌齐的摄取。

IF 2.4 4区医学

Experimental Neurobiology Pub Date : 2026-10-16 DOI: 10.5607/en26028

Songmin Lee, Kyeonghwan Kim, Hyungmin Kim, Min-Seok Oh, Kyungho Yoon, Subin Kwak, JiMin Kim, Gwan-Ho Lee, YoungSoo Kim, Jaeho Kim

{"title":"Focused Ultrasound as a Plasma Protein Binding-targeted Strategy to Enhance Brain Uptake of Donepezil.","authors":"Songmin Lee, Kyeonghwan Kim, Hyungmin Kim, Min-Seok Oh, Kyungho Yoon, Subin Kwak, JiMin Kim, Gwan-Ho Lee, YoungSoo Kim, Jaeho Kim","doi":"10.5607/en26028","DOIUrl":"https://doi.org/10.5607/en26028","url":null,"abstract":"Donepezil, a reversible acetylcholinesterase inhibitor, is widely used for the symptomatic treatment of Alzheimer's disease (AD). Although higherdose donepezil has been shown to provide additional clinical benefit, dose escalation is often limited by cholinergic adverse effects. Given that approximately 96% of circulating donepezil is bound to plasma proteins, especially albumin, we hypothesized that increasing its unbound fraction from albumin may improve brain delivery without increasing the administered dose. To achieve this goal, herein we examined whether the donepezil-albumin complex can be dissociated by low-intensity focused ultrasound (FUS) in vitro. Then brain uptake of donepezil was evaluated in mice receiving intravenous donepezil followed by targeted brain FUS stimulation. As a result, FUS significantly increased unbound fraction of donepezil at the targeted region in vitro, resulting in a 41.1% increase of donepezil diffusion into dialysis cassettes compared with non-sonicated controls. In mice receiving intravenous donepezil, targeted brain FUS stimulation increased brain donepezil concentrations by 52.7% at 15-min post-administration time. These findings suggest that low-intensity FUS enhances brain uptake of donepezil, potentially through modulation of donepezil-albumin binding, and support further investigation of plasma protein binding-targeted brain drug delivery.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149192236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Potential Link between Psychoneurological Impairment and Metabolic Stressors: Implications for Metabolic Encephalopathy. 精神神经损伤与代谢应激源之间的潜在联系：代谢性脑病的意义。

IF 2.4 4区医学

Experimental Neurobiology Pub Date : 2026-09-01 DOI: 10.5607/en26023

So Jung Park, So Yeong Cheon

{"title":"A Potential Link between Psychoneurological Impairment and Metabolic Stressors: Implications for Metabolic Encephalopathy.","authors":"So Jung Park, So Yeong Cheon","doi":"10.5607/en26023","DOIUrl":"https://doi.org/10.5607/en26023","url":null,"abstract":"Metabolic derangement is considered as a key underlying cause and contributor of metabolic encephalopathy, which is featured by cognitive decline, psychiatric symptoms, and severe coma. Clinical and preclinical studies have demonstrated that malnutrition, electrolyte derangements, toxic agents, and organ failure lead to metabolic disturbances including hyper/hypoglycaemia, hyperammonaemia, vitamin deficiency, hyper/hypokalaemia, hyper/hyponatraemia, and hyper/hypoferraemia. These metabolic stressors result in cognitive impairment and changed mental health. Because metabolic imbalance is often attributed to abnormalities in multiple factors rather than one factor, its distinction and management are critical. In cases of severe metabolic imbalances, it is recommended to identify such abnormalities using multiple strategies. Given that impaired brain function is difficult to recover, long-term dietary regulation and proper management are required by considering underlying diseases or conditions. Hence, by exploring the connections between metabolic imbalances (e.g., glucose, ammonia, indoxyl sulfate, electrolyte ions, and vitamins), and cognitive and mental health, this review provides evidence that emphasises the critical importance of management of metabolic health. Comprehending psychoneurological impairment caused by metabolic disturbances highlights the potential overlap with cognitive/mental symptoms of underlying conditions. Therefore, identifying the key pathological mechanisms of metabolic stress-induced psychoneurological impairment provides valuable insignts into the development of effective management and therapeutic approaches.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148864457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

MCHR1 in Both Dopaminergic Neurons and Astrocytes in the SNpc Contributes to Acupuncture's Anti-Parkinsonian Effects. SNpc中多巴胺能神经元和星形胶质细胞中的MCHR1参与了针灸的抗帕金森效应

IF 2.4 4区医学

Experimental Neurobiology Pub Date : 2026-08-31 Epub Date: 2026-05-06 DOI: 10.5607/en26012

Hyowon Lee, Ju-Young Oh, Heesu Na, Mijin Yun, Jae-Nam Park, Hi-Joon Park, Min-Ho Nam

{"title":"MCHR1 in Both Dopaminergic Neurons and Astrocytes in the SNpc Contributes to Acupuncture's Anti-Parkinsonian Effects.","authors":"Hyowon Lee, Ju-Young Oh, Heesu Na, Mijin Yun, Jae-Nam Park, Hi-Joon Park, Min-Ho Nam","doi":"10.5607/en26012","DOIUrl":"10.5607/en26012","url":null,"abstract":"Acupuncture stimulation at the GB34 acupoint has been reported to alleviate motor dysfunction in Parkinson's disease (PD) by activating the lateral hypothalamic melanin concentrating hormone (MCH) neurons projecting to the substantia nigra pars compacta (SNpc). MCH receptor 1 (MCHR1) signaling is also known to be essential for the anti-Parkinsonian effects of acupuncture. However, the cellular distribution of MCHR1 and its cell type-specific contributions to the therapeutic effects of acupuncture in PD remain largely unexplored. Here, we show that MCHR1 is expressed in both dopaminergic neurons and astrocytes within the SNpc, with higher expression in dopaminergic neurons. We further demonstrate that cell-type-specific gene-silencing of MCHR1 in either dopaminergic neurons or astrocytes significantly blocks acupuncture-induced motor recovery and dopaminergic neuron protection. These findings indicate that both neuronal and astrocytic MCHR1 contribute to the anti-Parkinsonian effects of acupuncture. Together, this study provides new insight into MCHR1 as a potential therapeutic target for PD.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":" ","pages":"187-197"},"PeriodicalIF":2.4,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13541635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835823","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}

引用次数: 0

Blockade of IRE1-XBP1 Signaling Pathway Ameliorates IL-6-dependent Nerve Damage and Neuron Pyroptosis after Subarachnoid Hemorrhage in Mice. 阻断IRE1-XBP1信号通路可改善小鼠蛛网膜下腔出血后il -6依赖性神经损伤和神经元焦亡

IF 2.4 4区医学

Experimental Neurobiology Pub Date : 2026-08-31 Epub Date: 2026-04-29 DOI: 10.5607/en26003

Huangsuo Wang, Huoquan Tang, Jie Zhou, Bo Li, Xingguang Ren, Yangkai Huang, Zhengkun Liu, Jingjing Hu, Xiaofang Sun, Jian Lu

{"title":"Blockade of IRE1-XBP1 Signaling Pathway Ameliorates IL-6-dependent Nerve Damage and Neuron Pyroptosis after Subarachnoid Hemorrhage in Mice.","authors":"Huangsuo Wang, Huoquan Tang, Jie Zhou, Bo Li, Xingguang Ren, Yangkai Huang, Zhengkun Liu, Jingjing Hu, Xiaofang Sun, Jian Lu","doi":"10.5607/en26003","DOIUrl":"10.5607/en26003","url":null,"abstract":"Subarachnoid hemorrhage (SAH) often results in severe neurological impairment. While spliced X-box binding protein 1 (XBP1s) has been implicated in brain injury, its specific role and mechanism in SAH-induced mice remain unclear. A murine SAH model was established to explore the function of XBP1 knockdown. Neurological function was evaluated through behavioral tests, brain edema measurement, and hematoxylin and eosin staining. Blood-brain barrier (BBB) integrity and neuronal pyroptosis were assessed using Evans blue extravasation, western blotting, immunofluorescence and LDH release assay. The direct interaction of IL-6 by XBP1s was confirmed using chromatin immunoprecipitation and luciferase reporter assays. Finally, the functional central to our hypothesis was verified by administering exogenous IL-6 or IL-6 blocking antibody to SAH mice. We found that XBP1s and p-IRE1 were significantly up-regulated after SAH. Knockdown of XBP1 ameliorated neurological deficits, preserved BBB integrity (as indicated by increased ZO-1/Occludin and reduced Evans blue leakage), and suppressed neuronal pyroptosis, evidenced by decreased levels of pyroptosis-related proteins and LDH release. Mechanistically, XBP1s was identified as a direct transcriptional enhancer of IL-6. In the mouse SAH model, the protective effects of XBP1 knockdown on the BBB and against pyroptosis were effectively abolished by the exogenous administration of IL-6 and were comparable to administration of the IL-6 blocking antibody. The IRE1-XBP1s signaling axis played an important role in SAH-induced neuronal damage and pyroptosis by directly up-regulating IL-6 expression. Inhibition of this axis represents a mechanistically grounded and promising strategy for SAH intervention.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":" ","pages":"198-215"},"PeriodicalIF":2.4,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13541636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766602","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}

引用次数: 0

Orofacial Central Pattern Generators: Neuroanatomical and Clinical Insights into Sensory, Motor, Emotional Integration. 口面部中枢模式发生器：感觉、运动、情绪整合的神经解剖学和临床见解。

IF 2.4 4区医学

Experimental Neurobiology Pub Date : 2026-08-31 Epub Date: 2026-05-11 DOI: 10.5607/en26009

Yong-Shin Hong, Young-Seok Park

{"title":"Orofacial Central Pattern Generators: Neuroanatomical and Clinical Insights into Sensory, Motor, Emotional Integration.","authors":"Yong-Shin Hong, Young-Seok Park","doi":"10.5607/en26009","DOIUrl":"10.5607/en26009","url":null,"abstract":"Orofacial behaviors such as mastication, swallowing, and phonation are not organized as simple reflex chains but are generated and coordinated by intrinsic brainstem networks known as central pattern generators (CPGs). Although the existence and organization of these circuits are well established in animal models, direct evidence for their microcircuit organization in humans remains limited, and current human interpretations rely largely on lesion-based, neurophysiological, and imaging-based inference. In this review, we synthesize neuroanatomical, neurophysiological, and clinical evidence to propose a network-centric framework for orofacial motor control. We describe the hierarchical organization of the orofacial CPG system across sensory input nuclei, premotor pattern-forming networks within the pontomedullary reticular formation, cranial motor output nuclei, and supranuclear modulation by cortical, basal ganglia, cerebellar, and limbic systems. Within this architecture, orofacial motor behaviors are conceptualized as a functional continuum in which somatic, visceral, and emotional signals converge to shape rhythmic and sequential motor output. Based on this circuit framework, we classify orofacial CPG dysfunction into four pathophysiological categories-sensory deafferentation, intrinsic pattern generator disturbances, motor output impairments, and supranuclear dysmodulation-emphasizing that failures of pattern generation are primarily expressed as deficits in timing and coordination rather than simple muscle weakness. Finally, we discuss circuit-informed implications for rehabilitation, highlighting how sensory priming, non-invasive brain stimulation, and rhythmic entrainment may promote functional recovery by reweighting residual brainstem-supranuclear networks. By reframing orofacial motor control as a distributed and hierarchically modulated network, this review provides a conceptual foundation for future experimental and translational studies of human brainstem motor systems.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":" ","pages":"173-186"},"PeriodicalIF":2.4,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13541637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147867414","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}

引用次数: 0

Endogenous Ecotropic Murine Leukemia Virus Promotes Prion Pathogenesis in Senescence-accelerated Mice. 内源性嗜生态小鼠白血病病毒促进衰老加速小鼠的朊病毒发病机制。

IF 2.4 4区医学

Experimental Neurobiology Pub Date : 2026-08-31 Epub Date: 2026-04-29 DOI: 10.5607/en26011

Min-Woo Choi, Mohd Najib Mostafa, Mo-Jong Kim, Byungki Jang, Myung-Ju Choi, Jae-Il Kim, Yong-Sun Kim, Eun-Kyoung Choi

{"title":"Endogenous Ecotropic Murine Leukemia Virus Promotes Prion Pathogenesis in Senescence-accelerated Mice.","authors":"Min-Woo Choi, Mohd Najib Mostafa, Mo-Jong Kim, Byungki Jang, Myung-Ju Choi, Jae-Il Kim, Yong-Sun Kim, Eun-Kyoung Choi","doi":"10.5607/en26011","DOIUrl":"10.5607/en26011","url":null,"abstract":"Among senescence-accelerated prone mice (SAMP), the SAMP8 and SAMP10 strains exhibit significant age-related deteriorations in learning and memory. Previous studies have reported that SAMP strains carry high level of Akv-type endogenous ecotropic murine leukemia virus (E-MuLV), whereas the senescence-accelerated resistant strain SAMR1 contains very low or undetectable levels of the virus. Retroviral infections, including MuLV, have been implicated in the acceleration of prion pathogenesis. Prion diseases are characterized by neuronal loss, spongiform degeneration, and astrogliosis and are caused by the infectious prion protein (PrPSc), which arises from the misfolding of the normal cellular prion protein (PrPC). Notably SAMP8 mice infected with scrapie exhibit shortened survival and increased PrPSc accumulation compared with SAMR1 mice. In this study, we investigated the role of endogenous E-MuLV to prion disease progression using senescence-accelerated mouse models. Following infection with the 22L scrapie strain, SAMP10 mice displayed significantly shortened survival compared with SAMR1 mice after both intracerebral (IC: 121.8±1.3 vs. 141.0±2.2 days) and intraperitoneal (IP: 184.4±1.3 vs. 216.2±2.7 days) inoculation. SAMP10 mice also showed earlier and more pronounced PrPSc accumulation during the clinical phase, along with enhanced vacuolation. Furthermore, in a cerebellar slice culture model of 22L scrapie infection, treatment with the antiretroviral drug zidovudine significantly reduced PrPSc accumulation in SAMP10 mice. Taken together, these findings suggest that endogenous E-MuLV contribute to the accelerated prion pathogenesis by promoting early and elevated PrPSc accumulation, leading to shortened survival.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":" ","pages":"216-226"},"PeriodicalIF":2.4,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13541634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766654","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}

引用次数: 0

A Novel Methodology for Temporal Analysis of Consumer Wearable Sleep Data: Feasibility and Application to Early Cognitive Impairment. 消费者可穿戴睡眠数据时间分析的新方法：可行性及其在早期认知障碍中的应用。

IF 2.4 4区医学

Experimental Neurobiology Pub Date : 2026-08-10 DOI: 10.5607/en26014

Sang-Ho Lee, Kwangsu Kim, Jisub Bae, Kiwon Choi, Da Hae Jung, Eun-Ji Park, Hyeon Chang Ju, Won-Seok Kang, Cheil Moon

{"title":"A Novel Methodology for Temporal Analysis of Consumer Wearable Sleep Data: Feasibility and Application to Early Cognitive Impairment.","authors":"Sang-Ho Lee, Kwangsu Kim, Jisub Bae, Kiwon Choi, Da Hae Jung, Eun-Ji Park, Hyeon Chang Ju, Won-Seok Kang, Cheil Moon","doi":"10.5607/en26014","DOIUrl":"https://doi.org/10.5607/en26014","url":null,"abstract":"While sleep disturbances are recognized as early markers of Alzheimer's disease (AD), the practical application of gold-standard polysomnography (PSG) for long-term monitoring is limited. This study aims to establish a novel methodological framework for the time-series analysis of sleep data collected via consumer-grade wearables and to explore whether this approach can detect differentiated signals across various stages of cognitive impairment. Daily sleep patterns of thirteen participants (5 healthy controls, 4 with aMCI, and 4 with mild AD) were monitored over three months using the Fitbit Charge 2. Rather than relying on aggregate nightly averages, we implemented a time-resolved analysis across 10-minute intervals to examine the temporal dynamics of sleep architecture. The proposed analysis revealed distinct, group-dependent temporal signatures. Specifically, the aMCI and AD groups exhibited shorter deep sleep during the early phase of the night, reduced REM sleep approximately three hours after sleep onset, and consistently elevated levels of light sleep and wake after sleep onset (WASO). These findings demonstrate that time-series analysis of wearable sleep data presents the potential to identify candidate digital phenotypes associated with cognitive decline. This study supports the feasibility of using longitudinal, dynamic sleep monitoring as an exploratory analytical framework warranting further validation for the detection of pathophysiological changes in older adults, shifting the focus from simple detection to the identification of candidate temporal sleep features. All reported findings are exploratory in nature and require replication in larger, independent cohorts.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148701117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

O-GlcNAc Modification of CEBPB Promotes Astrocytic Pyroptosis by Activating NLRP3 Inflammasome Through Transcriptional Activation of IKKβ. O-GlcNAc修饰CEBPB通过IKKβ转录激活NLRP3炎性体，促进星形细胞凋亡。

IF 2.4 4区医学

Experimental Neurobiology Pub Date : 2026-07-09 DOI: 10.5607/en26004

Xunhu Gu, Yufeng Chen, Lili Zheng, Xu Liu, Yanping Li, Shenjian Chen, Ruiqing Luo, Ming Li, Wei Wang

{"title":"O-GlcNAc Modification of CEBPB Promotes Astrocytic Pyroptosis by Activating NLRP3 Inflammasome Through Transcriptional Activation of IKKβ.","authors":"Xunhu Gu, Yufeng Chen, Lili Zheng, Xu Liu, Yanping Li, Shenjian Chen, Ruiqing Luo, Ming Li, Wei Wang","doi":"10.5607/en26004","DOIUrl":"10.5607/en26004","url":null,"abstract":"Major depressive disorder (MDD) is associated with astrocytic pyroptosis, but the mechanisms involved remain unclear. This study investigates how O-GlcNAc modification of CCAAT enhancer binding protein beta (CEBPB) influences its ability to regulate pyroptosis in astrocytes. In our study, primary astrocytes were exposed to LPS plus ATP to activate NLRP3 inflammasomes. Cell viability was assessed by CCK8 assay. IL-18 and IL-1β release was measured using ELISA. sWGA pull-down and Co-IP assays were performed to assess O-GlcNAc modification level of CEBPB. ChIP assay was used for promoter binding analysis, and ubiquitination detection was performed using Co-IP. Our results showed that LPS+ATP treatment significantly increased IKKβ expression in astrocytes, and IKKβ knockdown markedly reduced NLRP3 inflammasome activity and pyroptosis. Mechanistically, CEBPB transcriptionally activated IKKβ expression in astrocytes. Functionally, CEBPB knockdown ameliorated LPS+ATP-induced NLRP3 inflammasome activation and pyroptosis in astrocytes, which was abolished by IKKβ overexpression. In addition, O-GlcNAc modification at Thr235 enhanced CEBPB protein stability in astrocytes, driving NLRP3 inflammasome activation and pyroptosis. Collectively, these findings demonstrated that O-GlcNAc-modified CEBPB promoted pyroptosis in astrocytes during MDD progression by activating NLRP3 inflammasome through transcriptionally activating IKKβ.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":" ","pages":"255-268"},"PeriodicalIF":2.4,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148410849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Distinct Temporal Windows for Ventral Tegmental Area Dopamine Neurons are Required for Active Avoidance Learning. 主动回避学习需要腹侧被盖区多巴胺神经元的不同时间窗口。

IF 2.4 4区医学

Experimental Neurobiology Pub Date : 2026-07-08 DOI: 10.5607/en26019

Jung Hyun Pyo, Noah Koo, Joung-Hun Kim

{"title":"Distinct Temporal Windows for Ventral Tegmental Area Dopamine Neurons are Required for Active Avoidance Learning.","authors":"Jung Hyun Pyo, Noah Koo, Joung-Hun Kim","doi":"10.5607/en26019","DOIUrl":"10.5607/en26019","url":null,"abstract":"Ventral tegmental area (VTA) dopamine neurons play a central role in learning. Previous studies have shown that dopamine signaling is required for negative reinforcement and aversive instrumental learning, but whether this contribution is mediated by temporally distinct activity of dopaminergic neurons remains poorly understood. Here, using a two-way active avoidance paradigm, we monitored VTA dopamine neuron activity in animals that successfully acquired avoidance behavior and found that VTA dopamine neuron activity increased at two distinct time points, during the conditioned stimulus (CS) period and immediately after active avoidance. To test the functional significance of these signals, we chemogenetically inhibited VTA dopamine neurons. Global suppression of VTA dopamine neuron activity impaired avoidance learning. Furthermore, temporally restricted inhibition using optogenetics either during the CS period or immediately after successful avoidance was also sufficient to disrupt learning. We further mapped downstream projections of VTA dopamine neurons and monitored dopamine release in the basolateral amygdala (BLA) and nucleus accumbens (NAc), revealing that dopamine release in these regions was differentially aligned with cue-related and post-avoidance components of VTA dopamine neuron activity. Together, these findings suggest that VTA dopamine neurons support aversive instrumental learning through temporally distinct activity patterns that are accompanied by region-specific dopamine release dynamics in the BLA and NAc.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":" ","pages":"243-254"},"PeriodicalIF":2.4,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148404176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Neuroprotective and Antidepressant Effects of Tenebrio molitor Larvae Hydrolysate in LPS-induced Neuroinflammation Models. 黄粉虫幼虫水解物对lps诱导的神经炎症模型的神经保护和抗抑郁作用。

IF 2.4 4区医学

Experimental Neurobiology Pub Date : 2026-06-30 Epub Date: 2026-04-01 DOI: 10.5607/en26002

Younsoo Byun, Jiaxiang Zheng, Yoonhwa Jeong, Jihyun Noh

{"title":"Neuroprotective and Antidepressant Effects of Tenebrio molitor Larvae Hydrolysate in LPS-induced Neuroinflammation Models.","authors":"Younsoo Byun, Jiaxiang Zheng, Yoonhwa Jeong, Jihyun Noh","doi":"10.5607/en26002","DOIUrl":"10.5607/en26002","url":null,"abstract":"Environmental pollution from synthetic drugs undermines Sustainable Development Goals while exhibiting limited efficacy and adverse effects in mood disorder treatments. Tenebrio molitor larvae (TM) demonstrate significant health benefits including anti-inflammatory, antioxidant, and cognitive enhancing effects. Enzymatic hydrolysis enhances protein bioactivity by improving digestibility and releasing bioactive peptides. This study evaluated neuroprotective effects of TM hydrolysates (TMH) against lipopolysaccharide (LPS)-induced neuroinflammation. Cell viability was measured by WST assay and cytotoxicity was measured by LDH release assay. Inflammatory cytokine mRNA levels were quantified by qRT-PCR, and NF-κB-, MAPKs-, and apoptosis-related biomarkers protein expressions were assessed by western blot. The TMH was administered intracerebroventricularly and LPS was injected intraperitoneally into ICR mice. Behavioral assessments were performed 24 h after LPS injection for sickness-like phenotypes and 28 h after for depressive-like behavior. Mice were sacrificed immediately after the behavior test to collect hippocampal tissue for cytokine mRNA analyses. TMH prevented LPS-induced sickness-like phenotypes and depressive-like behavior increases. Hippocampal IL-1β mRNA levels decreased significantly while IL-6, TNF-α, and IL-10 expression showed downward trends. Cell viability was preserved with reduced LDH release and attenuated upregulation of IL-1β, NF-κB, JNK, ERK, and Caspase-3 in PC-12 cells. TMH demonstrated robust protection against LPS-induced neuroinflammatory and behavioral alterations, indicating therapeutic potential for mood disorder interventions through sustainable, bioactive compound utilization. TMH mitigates both neurotoxic and depressive-like effects of systemic LPS in complementary cell and animal models, supporting its potential development as an eco-friendly, non-synthetic therapeutic agent for neuroinflammatory mood disorders.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":" ","pages":"144-157"},"PeriodicalIF":2.4,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13349716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147590934","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}

引用次数: 0