PMID- 37936947 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20231109 IS - 2517-729X (Print) IS - 2517-729X (Electronic) IS - 2517-729X (Linking) VI - 36 IP - 5 DP - 2023 TI - Single-nucleus transcriptome profiling of prefrontal cortex induced by chronic methamphetamine treatment. PG - e101057 LID - 10.1136/gpsych-2023-101057 [doi] LID - e101057 AB - BACKGROUND: Methamphetamine (METH) addiction causes a huge burden on society. The prefrontal cortex (PFC), associated with emotion and cognitive behaviours, is also involved in addiction neurocircuitry. Although bulk RNA sequencing has shown METH-induced gene alterations in the mouse PFC, the impact on different cell types remains unknown. AIMS: To clarify the effects of METH treatment on different cell types of the PFC and the potential pathways involved in METH-related disorders. METHODS: We performed single-nucleus RNA sequencing (snRNA-seq) to examine the transcriptomes of 20 465 nuclei isolated from the PFC of chronic METH-treated and control mice. Main cell types and differentially expressed genes (DEGs) were identified and confirmed by RNA fluorescence in situ hybridization(FISH). RESULTS: Six main cell types were identified depending on the single-cell nucleus sequencing; of particular interest were the mature oligodendrocytes in the PFC. The DEGs of mature oligodendrocytes were enriched in the myelin sheath, adenosine triphosphate (ATP) metabolic process, mitochondrial function and components, and so on. The messenger RNA levels of Aldoc and Atp5l (FISH) and the protein level of the mitochondrial membrane pore subunit TOM40 (immunofluorescence) decreased in the mature oligodendrocytes. Fast blue staining and transmission electron microscopy image indicated myelin damage, and the myelin thickness decreased in METH brains. CONCLUSIONS: snRNA-seq reveals altered transcriptomes of different cell types in mouse PFC induced by chronic METH treatment, underscoring potential relationships with psychiatric disorders. CI - (c) Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. FAU - Zeng, Kuan AU - Zeng K AD - Department of Psychiatry, Wuhan Mental Health Center, Wuhan, Hubei, China. AD - Research Center for Psychological and Health Sciences, China University of Geosciences, Wuhan, Hubei, China. FAU - Yu, Xuan AU - Yu X AD - Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Education Ministry/Hubei Province of China for Neurological Disorders, Huazhong University of Science and Technology Tongji Medical College, Wuhan, Hubei, China. FAU - Wei, Zhen AU - Wei Z AD - Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Education Ministry/Hubei Province of China for Neurological Disorders, Huazhong University of Science and Technology Tongji Medical College, Wuhan, Hubei, China. AD - Department of Pathology, Maternal and Child Hospital of Hubei Province, Huazhong University of Science and Technology Tongji Medical College, Wuhan, Hubei, China. FAU - Wu, Yong AU - Wu Y AD - Department of Psychiatry, Wuhan Mental Health Center, Wuhan, Hubei, China. AD - Research Center for Psychological and Health Sciences, China University of Geosciences, Wuhan, Hubei, China. FAU - Wang, Jianzhi AU - Wang J AD - Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Education Ministry/Hubei Province of China for Neurological Disorders, Huazhong University of Science and Technology Tongji Medical College, Wuhan, Hubei, China. AD - Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu, China. FAU - Liu, Rong AU - Liu R AD - Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Education Ministry/Hubei Province of China for Neurological Disorders, Huazhong University of Science and Technology Tongji Medical College, Wuhan, Hubei, China. FAU - Li, Yi AU - Li Y AUID- ORCID: 0000-0002-8876-0041 AD - Department of Psychiatry, Wuhan Mental Health Center, Wuhan, Hubei, China. AD - Research Center for Psychological and Health Sciences, China University of Geosciences, Wuhan, Hubei, China. FAU - Wang, Xiaochuan AU - Wang X AUID- ORCID: 0000-0001-8207-0042 AD - Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Education Ministry/Hubei Province of China for Neurological Disorders, Huazhong University of Science and Technology Tongji Medical College, Wuhan, Hubei, China. AD - Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu, China. LA - eng PT - Journal Article DEP - 20231102 PL - England TA - Gen Psychiatr JT - General psychiatry JID - 101735271 PMC - PMC10626793 OTO - NOTNLM OT - Behavior, Addictive OT - Brain OT - Central Nervous System OT - Prefrontal Cortex COIS- Competing interests: None declared. EDAT- 2023/11/08 06:43 MHDA- 2023/11/08 06:44 PMCR- 2023/11/02 CRDT- 2023/11/08 03:57 PHST- 2023/03/26 00:00 [received] PHST- 2023/10/01 00:00 [accepted] PHST- 2023/11/08 06:44 [medline] PHST- 2023/11/08 06:43 [pubmed] PHST- 2023/11/08 03:57 [entrez] PHST- 2023/11/02 00:00 [pmc-release] AID - gpsych-2023-101057 [pii] AID - 10.1136/gpsych-2023-101057 [doi] PST - epublish SO - Gen Psychiatr. 2023 Nov 2;36(5):e101057. doi: 10.1136/gpsych-2023-101057. eCollection 2023.