Boosting neuronal activity-driven mitochondrial DNA transcription improves cognition in aged mice.

Autor: Li W; Department of Neurology of Second Affiliated Hospital and Liangzhu Laboratory, School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou, China.; Affiliated Mental Health Center and Hangzhou Seventh People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.; MOE Frontier Science Center for Brain Science and Brain-machine Integration, State Key Laboratory of Brain-machine Intelligence, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, Hangzhou, China., Li J; Department of Neurology of Second Affiliated Hospital and Liangzhu Laboratory, School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou, China.; Affiliated Mental Health Center and Hangzhou Seventh People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.; MOE Frontier Science Center for Brain Science and Brain-machine Integration, State Key Laboratory of Brain-machine Intelligence, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, Hangzhou, China., Li J; Department of Neurology of Second Affiliated Hospital and Liangzhu Laboratory, School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou, China.; Affiliated Mental Health Center and Hangzhou Seventh People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.; MOE Frontier Science Center for Brain Science and Brain-machine Integration, State Key Laboratory of Brain-machine Intelligence, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, Hangzhou, China., Wei C; Department of Neurology of Second Affiliated Hospital and Liangzhu Laboratory, School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou, China.; Affiliated Mental Health Center and Hangzhou Seventh People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.; MOE Frontier Science Center for Brain Science and Brain-machine Integration, State Key Laboratory of Brain-machine Intelligence, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, Hangzhou, China., Laviv T; Department of Physiology and Pharmacology, Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel.; Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel., Dong M; Department of Neurology of Second Affiliated Hospital and Liangzhu Laboratory, School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou, China.; Affiliated Mental Health Center and Hangzhou Seventh People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.; MOE Frontier Science Center for Brain Science and Brain-machine Integration, State Key Laboratory of Brain-machine Intelligence, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, Hangzhou, China., Lin J; Department of Neurology of Second Affiliated Hospital and Liangzhu Laboratory, School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou, China.; Affiliated Mental Health Center and Hangzhou Seventh People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.; MOE Frontier Science Center for Brain Science and Brain-machine Integration, State Key Laboratory of Brain-machine Intelligence, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, Hangzhou, China., Calubag M; Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA.; William S. Middleton Memorial Veterans Hospital, Madison, WI, USA., Colgan LA; Department of Neuronal Signal Transduction, Max Planck Florida Institute for Neuroscience, Jupiter, FL, USA., Jin K; Department of Neurology of Second Affiliated Hospital and Liangzhu Laboratory, School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou, China.; Affiliated Mental Health Center and Hangzhou Seventh People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.; MOE Frontier Science Center for Brain Science and Brain-machine Integration, State Key Laboratory of Brain-machine Intelligence, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, Hangzhou, China., Zhou B; Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University, Beijing, China., Shen Y; MOE Frontier Science Center for Brain Science and Brain-machine Integration, State Key Laboratory of Brain-machine Intelligence, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, Hangzhou, China., Li H; MOE Frontier Science Center for Brain Science and Brain-machine Integration, State Key Laboratory of Brain-machine Intelligence, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, Hangzhou, China., Cui Y; MOE Frontier Science Center for Brain Science and Brain-machine Integration, State Key Laboratory of Brain-machine Intelligence, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, Hangzhou, China., Gao Z; MOE Frontier Science Center for Brain Science and Brain-machine Integration, State Key Laboratory of Brain-machine Intelligence, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, Hangzhou, China., Li T; Affiliated Mental Health Center and Hangzhou Seventh People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.; MOE Frontier Science Center for Brain Science and Brain-machine Integration, State Key Laboratory of Brain-machine Intelligence, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, Hangzhou, China., Hu H; Affiliated Mental Health Center and Hangzhou Seventh People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.; MOE Frontier Science Center for Brain Science and Brain-machine Integration, State Key Laboratory of Brain-machine Intelligence, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, Hangzhou, China.; Research Units for Emotion and Emotion disorders, Chinese Academy of Medical Sciences, Beijing, China., Yasuda R; Department of Neuronal Signal Transduction, Max Planck Florida Institute for Neuroscience, Jupiter, FL, USA., Ma H; Department of Neurology of Second Affiliated Hospital and Liangzhu Laboratory, School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou, China.; Affiliated Mental Health Center and Hangzhou Seventh People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.; MOE Frontier Science Center for Brain Science and Brain-machine Integration, State Key Laboratory of Brain-machine Intelligence, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, Hangzhou, China.; Research Units for Emotion and Emotion disorders, Chinese Academy of Medical Sciences, Beijing, China.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2024 Dec 20; Vol. 386 (6728), pp. eadp6547. Date of Electronic Publication: 2024 Dec 20.
DOI: 10.1126/science.adp6547
Abstrakt: Deciphering the complex interplay between neuronal activity and mitochondrial function is pivotal in understanding brain aging, a multifaceted process marked by declines in synaptic function and mitochondrial performance. Here, we identified an age-dependent coupling between neuronal and synaptic excitation and mitochondrial DNA transcription (E-TC mito ), which operates differently compared to classic excitation-transcription coupling in the nucleus (E-TC nuc ). We demonstrated that E-TC mito repurposes molecules traditionally associated with E-TC nuc to regulate mitochondrial DNA expression in areas closely linked to synaptic activation. The effectiveness of E-TC mito weakens with age, contributing to age-related neurological deficits in mice. Boosting brain E-TC mito in aged animals ameliorated these impairments, offering a potential target to counteract age-related cognitive decline.
Databáze: MEDLINE
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