Loss of neuronal Tet2 enhances hippocampal-dependent cognitive function.

Autor:	Pratt KJB; Department of Anatomy, University of California San Francisco, 513 Parnassus Avenue, Box 0452, San Francisco, CA 94143, USA; Developmental and Stem Cell Biology Graduate Program, University of California San Francisco, San Francisco, CA 94143, USA., Shea JM; Department of Anatomy, University of California San Francisco, 513 Parnassus Avenue, Box 0452, San Francisco, CA 94143, USA., Remesal-Gomez L; Department of Anatomy, University of California San Francisco, 513 Parnassus Avenue, Box 0452, San Francisco, CA 94143, USA., Bieri G; Department of Anatomy, University of California San Francisco, 513 Parnassus Avenue, Box 0452, San Francisco, CA 94143, USA., Smith LK; Department of Anatomy, University of California San Francisco, 513 Parnassus Avenue, Box 0452, San Francisco, CA 94143, USA; Biomedical Sciences Graduate Program, University of California San Francisco, San Francisco, CA 94143, USA., Couthouis J; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA., Chen CP; Developmental and Stem Cell Biology Graduate Program, University of California San Francisco, San Francisco, CA 94143, USA., Roy IJ; Developmental and Stem Cell Biology Graduate Program, University of California San Francisco, San Francisco, CA 94143, USA., Gontier G; Department of Anatomy, University of California San Francisco, 513 Parnassus Avenue, Box 0452, San Francisco, CA 94143, USA. Electronic address: gontier.geraldine@gmail.com., Villeda SA; Department of Anatomy, University of California San Francisco, 513 Parnassus Avenue, Box 0452, San Francisco, CA 94143, USA; Developmental and Stem Cell Biology Graduate Program, University of California San Francisco, San Francisco, CA 94143, USA; Biomedical Sciences Graduate Program, University of California San Francisco, San Francisco, CA 94143, USA; Department of Physical Therapy and Rehabilitation Science, San Francisco, CA 94143, USA; Bakar Aging Research Institute, San Francisco, CA 94143, USA. Electronic address: saul.villeda@ucsf.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2022 Nov 08; Vol. 41 (6), pp. 111612.
DOI:	10.1016/j.celrep.2022.111612
Abstrakt:	DNA methylation has emerged as a critical modulator of neuronal plasticity and cognitive function. Notwithstanding, the role of enzymes that demethylate DNA remain to be fully explored. Here, we report that loss of ten-eleven translocation methylcytosine dioxygenase 2 (Tet2), which catalyzes oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), in adult neurons enhances cognitive function. In the adult mouse hippocampus, we detected an enrichment of Tet2 in neurons. Viral-mediated neuronal overexpression and RNA interference of Tet2 altered dendritic complexity and synaptic-plasticity-related gene expression in vitro. Overexpression of neuronal Tet2 in adult hippocampus, and loss of Tet2 in adult glutamatergic neurons, resulted in differential hydroxymethylation associated with genes involved in synaptic transmission. Functionally, overexpression of neuronal Tet2 impaired hippocampal-dependent memory, while loss of neuronal Tet2 enhanced memory. Ultimately, these data identify neuronal Tet2 as a molecular target to boost cognitive function. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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