title: Social stress in adolescents induces depression and brain-region-specific modulation of the transcription factor MAX.
abstract: 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.
authors.affiliation: Department of Pharmacology, Biomedical Sciences Institute, University of Sao Paulo, Sao Paulo, Brazil.|National Institute for Developmental Psychiatry (INCT-CNPq), Department of Psychiatry, Institute of Psychiatry, University of Sao Paulo Medical School, Sao Paulo, Brazil.
authors.forename: L S
authors.initials: LS
authors.lastname: Resende
authors.affiliation: Department of Pharmacology, Biomedical Sciences Institute, University of Sao Paulo, Sao Paulo, Brazil.|National Institute for Developmental Psychiatry (INCT-CNPq), Department of Psychiatry, Institute of Psychiatry, University of Sao Paulo Medical School, Sao Paulo, Brazil.
authors.forename: C E
authors.initials: CE
authors.lastname: Amaral
authors.affiliation: National Institute for Developmental Psychiatry (INCT-CNPq), Department of Psychiatry, Institute of Psychiatry, University of Sao Paulo Medical School, Sao Paulo, Brazil.
authors.forename: R B S
authors.initials: RB
authors.lastname: Soares
authors.affiliation: Department of Physiology and Biophysics, Biomedical Sciences Institute, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: A S
authors.initials: AS
authors.lastname: Alves
authors.affiliation: Department of Pharmacology, Biomedical Sciences Institute, University of Sao Paulo, Sao Paulo, Brazil.|National Institute for Developmental Psychiatry (INCT-CNPq), Department of Psychiatry, Institute of Psychiatry, University of Sao Paulo Medical School, Sao Paulo, Brazil.
authors.forename: L
authors.initials: L
authors.lastname: Alves-Dos-Santos
authors.affiliation: Department of Physiology and Biophysics, Biomedical Sciences Institute, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: L R G
authors.initials: LR
authors.lastname: Britto
authors.affiliation: Department of Pharmacology, Biomedical Sciences Institute, University of Sao Paulo, Sao Paulo, Brazil.|National Institute for Developmental Psychiatry (INCT-CNPq), Department of Psychiatry, Institute of Psychiatry, University of Sao Paulo Medical School, Sao Paulo, Brazil.
authors.forename: S
authors.identifier: 0000-0001-9511-653X
authors.initials: S
authors.lastname: Chiavegatto
mesh_terms: D000367:Age Factors; D000818:Animals; D001007:Anxiety / Q000235:genetics / Q000503:physiopathology; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics*; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D003866:Depressive Disorder / Q000235:genetics* / Q000503:physiopathology*; D004195:Disease Models, Animal; D004291:Dominance-Subordination; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009415:Nerve Net / Q000502:physiology; D009473:Neuronal Plasticity / Q000235:genetics / Q000502:physiology; D012931:Social Environment
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C499330:MAX protein, human