Social stress in adolescents induces depression and brain-region-specific modulation of the transcription factor MAX

Autor(es)

Resende, L. S. ; Amaral, C. E. ; Soares, R. B. S. ; Alves, A. S. ; Alves-dos-Santos, L. ; Britto, L. R. G. ; Chiavegatto, S.

• Tipo de documento: Artigo Científico
• Fonte: TRANSLATIONAL PSYCHIATRY; v. 6, OCT 11 2016.
• Citações Web of Science: 2

Resumo

MAX is a conserved constitutive small phosphoprotein from a network of transcription factors that are extensively studied in tumorigenesis and whose functions affect cell proliferation, differentiation and death. Inspired by its higher expression during development and in regions involved in emotional behaviors, we hypothesized its involvement in cerebral changes caused by early-life stress. We studied the effects of repeated social stress during adolescence on behaviors and on MAX and its putative partner MYC. Thirty-day-old C57BL/6 male mice underwent brief daily social defeat stress from an adult aggressor for 21 days. Following social stress episodes and housing in social groups after each defeat, adolescent mice exhibit depressive-like, but not anxiety-like behaviors and show higher MAX nuclear immunoreactivity in hippocampal (HC) but not prefrontal cortical (PFC) neurons. Conversely, MAX immunoreactivity is lower in the striatum (ST) of defeated adolescents. The positive correlation between MAX and MYC levels in the PFC revealed disruptions in both the HC and ST. The changes in MAX protein levels are not due to differential gene expression or protein degradation in those regions, suggesting that posttranscriptional modifications occurred. These findings indicate that repeated, brief social defeat in adolescent male mice, combined with group housing, is a useful protocol to study a subtype of depression that is dissociated from generalized (non-social) anxiety. To our knowledge, this is the first report of an association between dysregulation of the MAX-MYC network in the brain and a behavior, suggesting a novel approach for exploiting the neuroplasticity associated with depression. (AU)

• Processo FAPESP: 08/57896-8 - O Instituto Nacional da Psiquiatria do Desenvolvimento: uma nova abordagem para a psiquiatria tendo como foco as nossas crianças e o seu futuro
• Beneficiário: Eurípedes Constantino Miguel Filho
• Linha de fomento: Auxílio à Pesquisa - Temático
• Processo FAPESP: 09/01333-8 - Administração prolongada do ácido 13 cis-retinóico (isotretinoína) em camundongos machos adolescentes: comportamentos emocionais e níveis de RNA mensageiro de vários receptores de serotonina centrais
• Beneficiário: Silvana Chiavegatto
• Linha de fomento: Auxílio à Pesquisa - Regular