Acute stress in adolescence vs early adulthood following selective deletion of dysbindin-1A: Effects on anxiety, cognition and other schizophrenia-related phenotypes. (December 2019)

• Record Type: Journal Article
• Authors: Desbonnet, Lieve; O'Tuathaigh, Colm MP; O'Leary, Clare; Cox, Rachel; Tighe, Orna; Petit, Emilie I; Wilson, Steve; Waddington, John L
• Is Part Of: Journal of psychopharmacology. Volume 33:Number 12(2019)
• Page Start: 1610
• Page End: 1619
• Publication Date: 2019-12
• Subjects: Dysbindin-1A -- stress -- sex -- cognition -- anxiety; Psychopharmacology -- Periodicals; 615.78
• DOI: 10.1177/0269881119875465
• Languages: English
• ISSNs: 0269-8811

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.