ArticleMolecular psychiatry2026
ATP release from the amygdala-prefrontal pathway regulates vulnerability to social stress in male mice.
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Article in Molecular psychiatry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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18 authors.
Ding-Yu Wu *State Key Laboratory of Multi-organ Injury Prevention and Treatment, Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong Joint Laboratory for Psychiatric Disorders, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, 510515, Guangzhou, China.
Jian-Lin Wu *State Key Laboratory of Multi-organ Injury Prevention and Treatment, Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong Joint Laboratory for Psychiatric Disorders, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, 510515, Guangzhou, China.
Hao Chen *State Key Laboratory of Multi-organ Injury Prevention and Treatment, Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong Joint Laboratory for Psychiatric Disorders, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, 510515, Guangzhou, China.
Rong Luo *State Key Laboratory of Multi-organ Injury Prevention and Treatment, Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong Joint Laboratory for Psychiatric Disorders, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, 510515, Guangzhou, China.
Ying KongState Key Laboratory of Multi-organ Injury Prevention and Treatment, Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong Joint Laboratory for Psychiatric Disorders, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, 510515, Guangzhou, China.
Jian HuState Key Laboratory of Multi-organ Injury Prevention and Treatment, Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong Joint Laboratory for Psychiatric Disorders, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, 510515, Guangzhou, China.
Lang HuangState Key Laboratory of Multi-organ Injury Prevention and Treatment, Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong Joint Laboratory for Psychiatric Disorders, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, 510515, Guangzhou, China.
Ji-Hong LiuState Key Laboratory of Multi-organ Injury Prevention and Treatment, Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong Joint Laboratory for Psychiatric Disorders, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, 510515, Guangzhou, China.
Neng-Yuan HuState Key Laboratory of Multi-organ Injury Prevention and Treatment, Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong Joint Laboratory for Psychiatric Disorders, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, 510515, Guangzhou, China.
Meng-Ling WangState Key Laboratory of Multi-organ Injury Prevention and Treatment, Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong Joint Laboratory for Psychiatric Disorders, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, 510515, Guangzhou, China.
Shi-Yang JinState Key Laboratory of Multi-organ Injury Prevention and Treatment, Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong Joint Laboratory for Psychiatric Disorders, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, 510515, Guangzhou, China.
Xiao-Wen LiState Key Laboratory of Multi-organ Injury Prevention and Treatment, Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong Joint Laboratory for Psychiatric Disorders, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, 510515, Guangzhou, China.
Jian-Ming YangState Key Laboratory of Multi-organ Injury Prevention and Treatment, Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong Joint Laboratory for Psychiatric Disorders, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, 510515, Guangzhou, China.ORCID http://orcid.org/0000-0002-2079-1714
Zhao-Fa WuState Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, 100101, Beijing, China.ORCID http://orcid.org/0000-0003-2027-5194
Yu-Long LiState Key Laboratory of Membrane Biology, School of Life Sciences, Peking University, 100871, Beijing, China.ORCID http://orcid.org/0000-0002-9166-9919
Wei LuDepartment of Neurosurgery, Huashan Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, Minister of Education (MOE) Frontiers Center for Brain Science, Fudan University, 200032, Shanghai, China.
Yi-Hua ChenState Key Laboratory of Multi-organ Injury Prevention and Treatment, Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong Joint Laboratory for Psychiatric Disorders, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, 510515, Guangzhou, China. chenyihua@smu.edu.cn.ORCID http://orcid.org/0000-0002-7561-1645
Tian-Ming GaoState Key Laboratory of Multi-organ Injury Prevention and Treatment, Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong Joint Laboratory for Psychiatric Disorders, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, 510515, Guangzhou, China. tgao@smu.edu.cn.ORCID http://orcid.org/0000-0003-4594-9052
Funding
National Natural Science Foundation of China (National Science Foundation of China) 2021ZD0202704National Natural Science Foundation of China (National Science Foundation of China) 2022ZD0204700National Natural Science Foundation of China (National Science Foundation of China) 2022ZD0214300National Natural Science Foundation of China (National Science Foundation of China) 32271014National Natural Science Foundation of China (National Science Foundation of China) T2394535
Abstract
Extracellular adenosine triphosphate (ATP) dysregulation has been implicated in the pathogenesis of major depressive disorder. However, the mechanisms underlying ATP deficiency in the medial prefrontal cortex (mPFC) under stress conditions remain unclear. Here, we found that only stress-susceptible mice exhibited deficiencies in both the basal ATP levels and reward task-evoked ATP release, and these deficits could be reversed by treatment with fluoxetine. We also observed specific downregulation of Slc17a9, a gene encoding the vesicular nucleotide transporter (VNUT), in the mPFC of stress-susceptible mice. Conditional knockout of Slc17a9 in neurons (n-cKO), but not in astrocytes was sufficient to induce depressive-like behaviors following subthreshold social defeat stress (SSDS), accompanied by decreased basal extracellular ATP levels and impaired reward-evoked ATP release in the mPFC. Similar deficits were reproduced by specific knockdown of Slc17a9 in BLA
Indexed as
Adenosine TriphosphateStress, PsychologicalAmygdalaAnimalsDepressionDisease Models, AnimalFluoxetineMajor Depressive DisorderMaleMiceMice, Inbred C57BLMice, KnockoutNeural PathwaysNeuronsNucleotide Transport ProteinsPrefrontal CortexAdenosine TriphosphateFluoxetineNucleotide Transport ProteinsSlc17a9 protein, mouse
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.