Tet3 ablation in adult brain neurons increases anxiety-like behavior and regulates cognitive function in mice

• Type: Article in International Scientific Journal
• Date: 2020

Authors

Antunes, C (Author) Other; Da Silva, JD (Author) Other; Guerra Gomes, S (Author) Other; Alves, ND (Author) Other; Ferreira, F (Author) Other; Loureiro Campos, E (Author) Other; Branco, MR (Author) Other; Sousa, N (Author) Other; Reik, W (Author) Other; Pinto, L (Author) Other; Marques, CJ (Author) FMUP

Journal

Title: Molecular Psychiatry

ISSN: 1359-4184

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 37 Citations

Scopus - 36 Citations

Other information

Authenticus ID: P-00R-TVM

DOI: 10.1038/s41380-020-0695-7

Abstract (EN): TET3 is a member of the ten-eleven translocation (TET) family of enzymes which oxidize 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC). Tet3 is highly expressed in the brain, where 5hmC levels are most abundant. In adult mice, we observed that TET3 is present in mature neurons and oligodendrocytes but is absent in astrocytes. To investigate the function of TET3 in adult postmitotic neurons, we crossed Tet3 floxed mice with a neuronal Cre-expressing mouse line, Camk2a-CreERT2, obtaining a Tet3 conditional KO (cKO) mouse line. Ablation of Tet3 in adult mature neurons resulted in increased anxiety-like behavior with concomitant hypercorticalism, and impaired hippocampal-dependent spatial orientation. Transcriptome and gene-specific expression analysis of the hippocampus showed dysregulation of genes involved in glucocorticoid signaling pathway (HPA axis) in the ventral hippocampus, whereas upregulation of immediate early genes was observed in both dorsal and ventral hippocampal areas. In addition, Tet3 cKO mice exhibit increased dendritic spine maturation in the ventral CA1 hippocampal subregion. Based on these observations, we suggest that TET3 is involved in molecular alterations that govern hippocampal-dependent functions. These results reveal a critical role for epigenetic modifications in modulating brain functions, opening new insights into the molecular basis of neurological disorders.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 13