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

• Tipo: Artigo em Revista Científica Internacional
• Data: 2020

Autores

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

Revista

Título: Molecular Psychiatry

ISSN: 1359-4184

Editora: Springer Nature

Indexação

ISI Web of Knowledge - 37 Citações

Scopus - 36 Citações

Outras Informações

ID Authenticus: 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 13