Acute stress in adolescence vs early adulthood following selective deletion of dysbindin-1A: Effects on anxiety, cognition and other schizophrenia-related phenotypes.
J Psychopharmacol
; 33(12): 1610-1619, 2019 12.
Article
em En
| MEDLINE
| ID: mdl-31556815
ABSTRACT
BACKGROUND:
As exposure to stress has been linked to the onset and maintenance of psychotic illness, its pathogenesis may involve environmental stressors interacting with genetic vulnerability.AIM:
To establish whether acute stress interacts with a targeted mutation of the gene encoding the neurodevelopmental factor dystrobrevin-binding protein 1 (DTNBP1), resulting in a specific loss of the isoform dysbindin-1A, to influence schizophrenia-relevant phenotypes in mice during adolescence and adulthood.METHODS:
Male and female mice with a heterozygous or homozygous deletion of DTNBP1 were assessed in the open field test following acute restraint stress in adolescence (Day 35) and young adulthood (Day 60-70). Effects of acute restraint stress on memory retention in the novel object recognition test was also assessed in adulthood. Baseline corticosterone was measured in serum samples and, brain-derived neurotrophic factor (BDNF), glucocorticoid and mineralocorticoid receptor gene expression levels were measured in the hippocampus of adult mice.RESULTS:
In the open field, deletion of dysbindin-1A induced hyperactivity and attenuated the action of stress to reduce hyperactivity in adolescence but not in adulthood; in females deletion of dysbindin-1A attenuated the effect of acute stress to increase anxiety-related behaviour in adolescence but not in adulthood. In the novel object recognition test, deletion of dysbindin-1A impaired memory and also revealed an increase in anxiety-related behaviour and a decrease in hippocampal BDNF gene expression in males.CONCLUSIONS:
These data suggest that deletion of dysbindin-1A influences behaviours related to schizophrenia and anxiety more robustly in adolescence than in adulthood and that dysbindin-1A influences stress-related responses in a sex-dependent manner.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Ansiedade
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Esquizofrenia
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Estresse Psicológico
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Disbindina
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article