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Nicotine-induced transcriptional changes and mitochondrial dysfunction in the ventral tegmental area revealed by single-nucleus transcriptomics

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Journal of Genetics and Genomics 2024年第11期51卷 1237-1251页

作者： Lei Fan Boxin Liu Ru Yao Xia Gao Hongjuan Wang Sanjie Jiang Xiaomin Zheng Huan Chen Hongwei Hou Yong Liu Qingyuan Hu Anhui Institute of Optics and Fine Mechanics Hefei Institutes of Physical ScienceChinese Academy of SciencesHefeiAnhui 230000China University of Science and Technology of China HefeiAnhui 230000China Beijing Life Science Academy Beijing 100000China Key Laboratory of Tobacco Biological Effects and Biosynthesis Bejing 100000China China National Tobacco Quality Supervision&Test Center ZhengzhouHenan 450000China Key Laboratory of Tobacco Biological Effects ZhengzhouHenan 450000China BGI Genomics BGI-ShenzhenGuangdong 518018China

Nicotine is widely recognized as the primary contributor to tobacco *** studies have indicated that molecular and behavioral responses to nicotine are primarily mediated by ventral tegmental area(VTA)neurons,and accumulating evidence suggests that glia play prominent roles in nicotine ***,VTA neurons and glia have yet to be characterized at the transcriptional level during the progression of nicotine ***,a male mouse model of nicotine self-administration is established and the timing of three critical phases(pre-addiction,addicting,and post-addiction phase)is ***-nucleus RNA sequencing in the VTA at each phase is performed to comprehensively classify specific cell *** changes occurred during the addicting and post-addiction phases,with the addicting phase displaying highly dynamic neuroplasticity that profoundly impacts the transcription in each cell ***,significant transcriptional changes in energy metabolism-related genes are observed,accompanied by notable structural alterations in neuronal mitochondria during the progression of nicotine *** results provide insights into mechanisms underlying the progression of nicotine addiction,serving as an important resource for identifying potential molecular targets for nicotine cessation.

关键词： Single-nucleus transcriptomics ventral tegmental area Nicotine addiction Cell-type-specific alteration Mitochondrial dysfunction

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Potentiation of the lateral habenula-ventral tegmental area pathway underlines the susceptibility to depression in mice with chronic pain

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Science China(Life Sciences) 2024年第1期67卷 67-82页

作者： Chun-Kui Zhang Pan Wang Yuan-Yuan Ji Jian-Shuai Zhao Jun-Xiang Gu Xian-Xia Yan Hong-Wei Fan Ming-Ming Zhang Yu Qiao Xiao-Die Liu Bao-Juan Li Ming-Hui Wang Hai-Long Dong Hao-Hong Li Peng-Cheng Huang Yun-Qing Li Wu-Gang Hou Jin-Lian Li Tao Chen Department of Anatomy and K.K.Leung Brain Research Centre Fourth Military Medical UniversityXi’an 710032China Beijing Institute of Basic Medical Sciences Beijing 100850China Key Laboratory of Ministry of Public Health for Forensic Science Xi’an Jiaotong UniversityXi’an 710061China Department of Anesthesiology Xijing HospitalFourth Military Medical UniversityXi’an 710032China Department of Neurosurgery the Second Affiliated Hospital of Xian Jiaotong UniversityXi’an 710004China School of Biomedical Engineering Fourth Military Medical UniversityXi’an 710032China Affiliated Mental Health Centre and Hangzhou Seventh People’s Hospital Zhejiang University School of MedicineHangzhou 310013China The MOE Frontier Research Center of Brain&Brain-machine Integration Zhejiang University School of Brain Science and Brain MedicineHangzhou 310058China Department of Neurology The First Affiliated Hospital of Nanchang UniversityNanchang 330006China Department of Anatomy School of MedicineNorthwest UniversityXi’an 710069China

Chronic pain often develops severe mood changes such as ***,how chronic pain leads to depression remains elusive and the mechanisms determining individuals’responses to depression are largely *** we found that depression-like behaviors could only be observed in 67.9%of mice with chronic neuropathic pain,leaving 32.1%of mice with depression *** determined that the spike discharges of the ventral tegmental area(VTA)-projecting lateral habenula(LHb)glutamatergic(Glu)neurons were sequentially increased in sham,resilient and susceptible mice,which consequently inhibited VTA dopaminergic(DA)neurons through a LHbGlu-VTAGABA-VTADA ***,the LHbGlu-VTADA excitatory inputs were dampened via GABAB receptors in a pre-synaptic *** of LHb-VTA pathway largely affected the development of depressive symptoms caused by chronic *** study thus identifies a pivotal role of the LHb-VTA pathway in coupling chronic pain with depression and highlights the activity-dependent contribution of LHbGlu-to-VTADA inhibition in depressive behavioral regulation.

关键词： chronic pain depression lateral habenula ventral tegmental area dopamine susceptibility

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Effect of crocin carotenoid on BDNF and CREB gene expression in brain ventral tegmental area of morphine treated rats

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Asian Pacific Journal of Tropical Biomedicine 2018年第8期8卷 387-393页

作者： Marzieh Rezai Mehdi Mahmoodi Ayat Kaeidi Mojgan Noroozi Karimabad Alireza Khoshdel Mohammad Reza Hajizadeh Department of Clinical Biochemistry Faculty of Medicine Rafsanjan University of Medical Sciences Department of Clinical Biochemistry Afzalipoor Faculty of Medicine Kerman University of Medical Sciences Molecular Medicine Research Center Research Institute of Basic Medical Sciences Rafsanjan University of Medical Sciences Physiology-Pharmacology Research Center Research Institute of Basic Medical Sciences Rafsanjan University of Medical Sciences Department of Physiology and Pharmacology School of Medicine Rafsanjan University of Medical Sciences Department of Clinical Biochemistry Faculty of Medicine and Pistachio Safety Research Center Rafsanjan University of Medical Sciences

Objective: To investigate the effect of crocin carotenoid on BNDF and CREB gene expression in the brain ventral tegmental area(VTA) and the serum level of BDNF in morphine-treated rats compared to control. Methods: In this study, 40 male Wistar rats(200-250 g) were used in 5 experimental groups: 1) non morphine treat rats(control); 2) non morphine-treated rats with 25 mg/kg crocin carotenoid(i.p., for 21 d); 3) morphine treated rats(10 mg/kg twice a day, s.c., 21 d); 4 and 5) morphine-treated rats with 12.5 and 25 mg/kg crocin carotenoid, respectively. By the end of research, BDNF and CREB expression was determined by real-time-PCR method. ELISA analysis was also applied for assessing the serum BDNF level. Results: The data indicated that morphine treatment could cause a significant decrease in BDNF and CREB gene expression(P<0.01 and P<0.001, respectively) in brain VTA as well as serum level of BDNF(P<0.01) in comparison to control group. Treatment with 25 mg/kg crocin carotenoid caused a significant enhancement in BDNF and CREF gene expression(P<0.01 and P<0.05, respectively) and serum level of BDNF(P<0.01) in morphine-treated rats in comparison to morphine-treated group. Conclusions: Regarding to obtained results, crocin carotenoid can inhibit unfavorable effects of morphine on the neural system to some extent through enhancing BDNF and CREB gene expression in brain VTA and serum level of BDNF.

关键词： Morphine BDNF CREB Crocin ventral tegmental area Rat

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Local infusion of low, but not high, doses of alcohol into the anterior ventral tegmental area causes release of accumbal dopamine

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Open Journal of Psychiatry 2014年第1期4卷 53-59页

作者： Elisabet Jerlhag Jorgen A. Engel Section for Pharmacology Institute of Neuroscience and Physiology The Sahlgrenska Academy at the University of Gothenburg Gothenburg Sweden

The mesolimbic dopamine system consisting of dopaminergic neurons projecting from the ventral tegmental area (VTA) to the nucleus accumbens (***.) mediates the reinforcing effects of addictive drugs including alcohol. Given that VTA is a heterogeneous area and that alcohol, in rather low doses, interacts directly with ligand-gated ion channels, we hypothesised that low, rather than high, doses of alcohol into the VTA activate the mesolimbic dopamine system and that alcohol may have different effects in the anterior and posterior parts of the VTA. The present study was undertaken to investigate this hypothesis. The present series of experiment show that infusion of a low dose of alcohol (20 mM) into the anterior, but not posterior, part of the VTA increases accumbal dopamine release in rats. In addition, higher doses of alcohol (100 or 300 mM) into the anterior or posterior part of the VTA do not affect the release of dopamine in the ***., suggesting that low doses of alcohol can activate the mesolimbic dopamine system via mechanisms in the VTA. These data contribute to understanding the neuronal mechanisms underlying the dependence-producing properties of alcohol and could tentatively contribute to that new treatment strategies for alcohol use disorder can be developed.

关键词： Alcohol ventral tegmental area Nucleus Accumbens Dopamine Rats

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Prelimbic cortex and ventral tegmental area modulate synaptic plasticity in nucleus accumbens during cocaine-reinstated drug seeking

Prelimbic cortex and ventral tegmental area modulate synapti...

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中国神经科学学会第十届全国学术会议

作者： Haowei SHEN National Institute on Drug Dependence Peking University

Addictive drug use causes long-lasting changes in synaptic strength and dendritic spine morphology in the nucleus accumbens that might underlie the vulnerability to *** activity in mesocorticolimbic circuitry is required for reinstating cocaine seeking,its role in reinstatement-associated synaptic plasticity is not well *** rats extinguished from cocaine self-administration,we found potentiated synaptic strength（assessed as the AMPA/NMDA current amplitude ratio） and increased spine head diameter in medium spiny neurons in the accumbens core（NAcore）.The basal changes in synaptic strength and morphology in cocaine-extinguished animals were further augmented during cocaine-induced *** NAcore afferents contributing to cocaine reinstatement are glutamatergic inputs from the prelimbic prefrontal cortex（PL） and dopamine from the ventral tegmental area（VTA）.Pharmacological inhibition of either PL or VTA prevented cocaine-primed ***,inhibiting the PL further potentiated AMPA/NMDA and spine head diameter,while inactivating the VTA prevented the increase in AMPA/NMDA and spine diameter induced during cocaine-reinstated lever *** the importance of dopamine in the effects of VTA inhibition,both the increase in AMPA/NMDA and reinstated cocaine seeking were prevented by the combined systemic administration of dopamine Dl（SCH-23390） and D2（raclopride） *** data indicate that neuronal activity in the VTA and associated dopamine receptor stimulation is necessary for the synaptic potentiation induced in the NAcore during cocaine-induced ***,while activity in the PL is necessary for cocaine-induced reinstatement,it serves to inhibit the synaptic potentiation associated with cocaine-induced reinstatement,posing state-dependent regulation by the PL on cocaine-induced neuroadaptations.

关键词： prelimbic cortex ventral tegmental area synaptic plasticity cocaine addiction

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Activation of the ventral tegmental area Increased Wakefulness,Decreased NREM and REM sleep in Mice

Activation of the Ventral Tegmental Area Increased Wakefulne...

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中国睡眠研究会第九届学术年会

作者： Huan-Xin Sun Dian-Ru Wang Chen-Yao Wang Zhi-Li Huang Su-Rong Yang Department of Pharmacology School of Basic Medical SciencesFudan University

Introduction:The ventral tegmental area(VTA)is crucial for brain functions,such as voluntary movement,cognition,emotion,reward,and ***,the role of VTA in sleep-wake regulation when it is directly activated remains ***:The 129 male mice were bilaterally microinjected with CMV-hMDq-AAVinto ***2 weeks of postoperative recovery,the animals were implanted with electrodes for electroencephalograph(EEG)and electromyography(EMG)*** week later,the animals

关键词： pharmacogenetic approach sleep ventral tegmental area wakefulness

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Electroacupuncture treatment reverses morphine-induced physiological changes in dopaminergic neurons within the ventral tegmental area

Electroacupuncture treatment reverses morphine-induced physi...

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中国神经科学学会第四次会员代表大会暨第八届全国学术会议

作者： Ling HU,Ning-Ning CHU,Lin-Lin SUN,Rong ZHANG,Ji-Sheng HAN,Cai-Lian CUI~* Neuroscience Research Institute and Department of Neurobiology,Peking University Health Science Center,Key Laboratory of Neuroscience,the Ministry of Education and Ministry of Public Health,Beijing 100191,China

Chronic morphine administration decreases the size of dopamine(DA) neurons in the ventral tegmental area (VTA).These transient morphological changes are accompanied by a reduced sensitivity of morphine-induced conditioned place preference(CPP) after chronic exposure to the *** this study we examined alterations in the firing rate of DAergic neurons by means of extracellular recording following chronic morphine exposure and applied 100 Hz electroacupuncture(EA) treatment to reverse the reduced firing rate of these *** the first set of experiments we show that in rats,which received chronic morphine treatment for 14 days,a small dose of morphine was not able to induce a CPP response ***,the sensitivity to morphine was reinstated by consecutive EA treatment for 10 days. The electrophysiological response of VTA DA neurons to morphine was markedly reduced in chronic morphine-treated rats compared to saline-treated controls.A substantial recovery of the reactivity of VTA DA neurons to morphine was observed in rats that received 100 Hz EA for 10 *** findings suggest that 100 Hz EA is a potential therapy for the treatment of opiate addiction by normalizing the activity of VTA DA neurons.

关键词： conditioned place preference(CPP) dopamine neurons electroacupuncture(EA) morphine ventral tegmental area

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Effects of D-serine on the basolateral amygdala and ventral tegmental area in model rats with conditioned fear memory

Effects of D-serine on the basolateral amygdala and ventral ...

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中国神经科学学会第十届全国学术会议

作者： Ling-Lu SUN Ming-Xun ZHANG Jun HUANG Meng-Ya WANG Cell Electrophysiology Laboratory Wannan Medical College Rising-Star Group Wannan Medical College

Objective To explore the possible mechanisms underlying D-serine therapy of post-traumatic stress disorder（PTSD） by observing its effects on the basolateral amygdala（BLA） and ventral tegmental area（VTA） in model rats with conditioned fear *** A protocol of 3-day "sound- electric shock" paired stimulation was used to prepare rat model of conditioned fear memory indicated by an increase of percentage of freezing *** the extracellular recordings from BLA and VTA in the brain were conducted,and physiological functions including electrocardiograph,electromyography,skin conductance and body temperature were simultaneously monitored from the urethane-anesthetized normal and model rats（n=4）.Effects of D-serine（0.4 g/kg,i.p.） were observed as compared with saline（i.p.）.Results Although no significant differences of bioelectrical activities of BLA and VTA,and physiological functions were observed between normal and model rats,saline injection significantly increased firing rate only in BLA in normal rats,while in BLA and VTA in model ***,D-serine induced a significant increase of the firing rate of BLA and VTA in normal rats,but only of VTA in model ***,the increase of firing rate of VTA by D-serine was higher in model rats than in normal rats（P＜0.05）.Conclusion These preliminary results suggest D-serine may have more potent activating effects on VTA than BLA in model rats,and on VTA in model rats than in normal rats.

关键词： D-serine basolateral amygdala ventral tegmental area post-traumatic stress disorder

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Ethanol blocks long-term potentiation of GABAergic synapses in the ventral tegmental area involving mu-opioid receptors

Ethanol blocks long-term potentiation of GABAergic synapses ...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Yan-Zhong GUAN~(1,2),Jiang-Hong YE~1 1 Department of Anesthesiology,University of Medicine and Dentistry of New Jersey,New Jersey Medical School, Newark,NJ,07103,USA 2 Department of Physiology,Mudanjiang Medical University,Mudanjiang 157011,China

Objective It is well documented that ethanol exposure alters GABA(Y-aminobutyric acid)-releasing synapses,and ethanol addiction is associated with endogenous opioid *** evidence indicates that opioids block long-term potentiation in the fast inhibitory GABA receptor synapses(LTP) onto dopamine-containing neurons in the ventral tegmental area(VTA),a brain region essential for reward-seeking ***,how ethanol affects LTP is not *** present study is to explore the effects of ethanol on long-term potentiation of GABAergic synapses in the ventral tegmental *** Using whole-cell patch clamp methods we recorded evoked IPSCs from DA neurons in acute coronal midbrain slices of young Sprague-Dawley *** We report here that in acute midbrain slices from rats,clinically relevant concentrations of ethanol applied both in vitro and in vivo prevents LTP,which is reversed,respectively,by in vitro and in vivo administration of naloxone,a mu-opioid receptor(MOR) ***,the blockade of LTP induced by a brief in vitro ethanol treatment is mimicked by DAMGO([D-Ala2,N-MePhe4,Gly-ol]-enkephalin),a MOR ***-pulse ratios are similar in slices,24 h after in vivo injection with either saline or ***-cAMPS,a stable cAMP analog,and pCPT-cGMP, a cGMP analog,potentiate GABA-mediated inhibitory postsynaptic currents in slices from ethanol-treated rats, indicating that a single in vivo ethanol exposure does not maximally increase GABA ***,ethanol produces a long-lasting inability to generate *** Ethanol blocks long-term potentiation of GABAergic synapses in the ventral tegmental area involving *** neuroadaptations to ethanol might contribute to early stage of addiction.

关键词： ethanol long-term potentiation GABAergic synapses ventral tegmental area

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Brain region-specific roles of brain-derived neurotrophic factor in social stress-induced depressive-like behavior

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Neural Regeneration Research 2025年第1期20卷 159-173页

作者： Man Han Deyang Zeng Wei Tan Xingxing Chen Shuyuan Bai Qiong Wu Yushan Chen Zhen Wei Yufei Mei Yan Zeng Brain Science and Advanced Technology Institute Wuhan University of Science and TechnologyWuhanHubei ProvinceChina Geriatric Hospital Affiliated to Wuhan University of Science and Technology WuhanHubei ProvinceChina School of Public Health Wuhan University of Science and TechnologyWuhanHubei ProvinceChina

Brain-derived neurotrophic factor is a key factor in stress adaptation and avoidance of a social stress behavioral *** studies have shown that brain-derived neurotrophic factor expression in stressed mice is brain region–specific,particularly involving the corticolimbic system,including the ventral tegmental area,nucleus accumbens,prefrontal cortex,amygdala,and *** how brain-derived neurotrophic factor participates in stress processing in different brain regions will deepen our understanding of social stress *** this review,we discuss the expression and regulation of brain-derived neurotrophic factor in stress-sensitive brain regions closely related to the pathophysiology of *** focused on associated molecular pathways and neural circuits,with special attention to the brain-derived neurotrophic factor–tropomyosin receptor kinase B signaling pathway and the ventral tegmental area–nucleus accumbens dopamine *** determined that stress-induced alterations in brain-derived neurotrophic factor levels are likely related to the nature,severity,and duration of stress,especially in the above-mentioned brain regions of the corticolimbic ***,BDNF might be a biological indicator regulating stress-related processes in various brain regions.

关键词： amygdala chronic mild stress chronic social defeat stress corticolimbic system depression hippocampus medial prefrontal cortex nucleus accumbens social stress models ventral tegmental area

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