ArticleNature communications2024
Astrocytic ALKBH5 in stress response contributes to depressive-like behaviors in mice.
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48 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Bidirectional Mendelian Randomization and Colocalization Study of Memory B Cells and Major Depressive Disorder.Current medical science · 2026Pooled it
- Exploration of current situation of psychotropic drugs research and development in China based on drug clinical trials.Frontiers in psychiatry · 2025Pooled it
- Disrupted TFEB/GDNF-cAMP/ATP Coupling Underlies Astrocytic Dysfunction and Depression in LRRK2 G2019S Parkinson's Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- YTHDF1 modulates CAP1-mediated actin turnover to regulate synaptic function and anxiodepressive-like behaviors.Molecular psychiatry · 2026Article
- ALKBH5 activates creatine-driven thermogenesis by stabilizing CKB mRNA in response to cold.Nature metabolism · 2026Article
- A prefrontal cortex-piriform cortex circuit mediates diminished interest.Molecular psychiatry · 2026Article
- Unveiling the enigma of anxiety disorders and depression: from pathogenesis to treatment.Science China. Life sciences · 2026Review
- mNature reviews. Neuroscience · 2026Review
- ATP release from the amygdala-prefrontal pathway regulates vulnerability to social stress in male mice.Molecular psychiatry · 2026Article
- Phenotype-Specific Transcriptomic Responses to Glucocorticoid Signaling in the Prefrontal Cortex and Dorsal Raphe Nucleus Following Chronic Social Stress.International journal of molecular sciences · 2026Article
- FGF13 alleviates astrocytic apoptosis via JIP2 inhibition in the hippocampus and mitigates depression-like behavior.Journal of neuroinflammation · 2026Article
- Microglial Alkbh5 Deficiency Alleviates Chronic Restraint Stress-Induced Depression-like Behaviors in Mice.Neuroscience bulletin · 2026Article
- Cell-type-specific m1A dynamics are associated with microglial phenotypic transition and neuronal metabolic adaptation during spinal cord injury.PLoS computational biology · 2026Article
- Metabolic crosstalk in the ageing brain: astrocyte-neuron coupling as a target for homeostatic restoration and therapy.Translational neurodegeneration · 2026Review
- Cumulative mild stress during early life alters prefrontal astrocytic proteins and elevates peripheral S100B in young adult mice.Translational psychiatry · 2026Article
- Bidirectional association between immune-mediated diseases and major depressive disorder: evidence from cohort, genome-wide pleiotropic, and experimental studies.Molecular psychiatry · 2026Article
- A modified tail suspension test for the assessment of behavioral despair in mice after stroke.Acta pharmacologica Sinica · 2026Article
- Decoding causal m6A: a bioinformatics roadmap for psychiatric disorders.Briefings in bioinformatics · 2026Review
- m6A deficiency induces dopaminergic neurodegeneration and progressive parkinsonism through a pathogenic loop with mitochondria.The Journal of clinical investigation · 2026Article
- Microglial GPR35 Ameliorates Epileptogenesis and Neuroinflammation via PDGFA Domain 2 Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
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Authors and funding
18 authors.
Fang Guo *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, Guangzhou, China.
Jun Fan *Department of Anesthesia, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, Guangdong, China.
Jin-Ming Liu *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, Guangzhou, China.
Peng-Li KongKey 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, Guangzhou, China.
Jing RenKey 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, Guangzhou, China.
Jia-Wen MoKey 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, Guangzhou, China.
Cheng-Lin LuKey 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, Guangzhou, China.
Qiu-Ling ZhongKey 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, Guangzhou, China.
Liang-Yu ChenKey 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, Guangzhou, China.
Hao-Tian JiangKey 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, Guangzhou, China.
Canyuan ZhangKey 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, Guangzhou, China.
You-Lu WenDepartment of Psychology and Behavior, Guangdong 999 Brain Hospital, Institute for Brain Research and Rehabilitation, South China Normal University, Guangzhou, Guangdong, P. R. China.
Ting-Ting GuDepartment of Psychology and Behavior, Guangdong 999 Brain Hospital, Institute for Brain Research and Rehabilitation, South China Normal University, Guangzhou, Guangdong, P. R. China.
Shu-Ji LiKey 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, Guangzhou, China.
Ying-Ying FangKey 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, Guangzhou, China.
Bing-Xing PanDepartment of Biological Science, School of Life Science, Nanchang University, Nanchang, China.ORCID http://orcid.org/0000-0001-6404-4019
Tian-Ming GaoKey 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, Guangzhou, China.ORCID http://orcid.org/0000-0003-4594-9052
Xiong CaoKey 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, Guangzhou, China. caoxiong@smu.edu.cn.ORCID http://orcid.org/0000-0002-1889-4255
Funding
National Science Foundation of China | NSAF Joint Fund 32271062
Abstract
Epigenetic mechanisms bridge genetic and environmental factors that contribute to the pathogenesis of major depression disorder (MDD). However, the cellular specificity and sensitivity of environmental stress on brain epitranscriptomics and its impact on depression remain unclear. Here, we found that ALKBH5, an RNA demethylase of N6-methyladenosine (m6A), was increased in MDD patients' blood and depression models. ALKBH5 in astrocytes was more sensitive to stress than that in neurons and endothelial cells. Selective deletion of ALKBH5 in astrocytes, but not in neurons and endothelial cells, produced antidepressant-like behaviors. Astrocytic ALKBH5 in the mPFC regulated depression-related behaviors bidirectionally. Meanwhile, ALKBH5 modulated glutamate transporter-1 (GLT-1) m6A modification and increased the expression of GLT-1 in astrocytes. ALKBH5 astrocyte-specific knockout preserved stress-induced disruption of glutamatergic synaptic transmission, neuronal atrophy and defective Ca
Indexed as
AlkB Homolog 5, RNA DemethylaseAstrocytesMajor Depressive DisorderMice, KnockoutAdenosineAdultAnimalsBehavior, AnimalDepressionDisease Models, AnimalExcitatory Amino Acid Transporter 2FemaleHumansMaleMiceMice, Inbred C57BLAdenosineALKBH5 protein, humanALKBH5 protein, mouseAlkB Homolog 5, RNA DemethylaseExcitatory Amino Acid Transporter 2N-methyladenosine
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