Social stress in adolescents induces depression and brain-region-specific modulation of the transcription factor MAX
| Autor: | L. Alves-dos-Santos, R B S Soares, A.S. Alves, Luiz R.G. Britto, Silvana Chiavegatto, L S Resende, C E Amaral |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Dominance-Subordination Male medicine.medical_specialty Striatum Hippocampal formation Protein degradation Anxiety Social Environment FARMACOLOGIA Social defeat 03 medical and health sciences Cellular and Molecular Neuroscience Mice 0302 clinical medicine Internal medicine Neuroplasticity medicine Animals Biological Psychiatry Social stress Brain Mapping Depressive Disorder Mice Inbred BALB C Neuronal Plasticity Basic Helix-Loop-Helix Leucine Zipper Transcription Factors Age Factors Brain medicine.disease Psychiatry and Mental health Disease Models Animal 030104 developmental biology Endocrinology Schizophrenia Original Article Psychopharmacology Nerve Net Psychology 030217 neurology & neurosurgery Clinical psychology |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP Translational Psychiatry |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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