Social Defeat during Adolescence and Adulthood Differentially Induce BDNF-Regulated Immediate Early Genes

Abstract

Stressful life events generally enhance the vulnerability for the development of human psychopathologies such as anxiety disorders and depression. The incidence rates of adult mental disorders steeply rises during adolescence in parallel with a structural and functional reorganization of the neural circuitry underlying stress reactivity. However, the mechanisms underlying susceptibility to stress and manifestation of mental disorders during adolescence are little understood. We hypothesized that heightened sensitivity to stress during adolescence reflects age-dependent differences in the expression of activity-dependent genes involved in synaptic plasticity. Therefore, we compared the effect of social stress during adolescence with social stress in adulthood on the expression of a panel of genes linked to induction of long-term potentiation (LTP) and brain-derived neurotrophic factor (BDNF) signaling. We show that social defeat during adolescence and adulthood differentially regulates expression of the immediate early genes BDNF, Arc, Carp, and Tieg1, as measured by qPCR in tissue lysates from prefrontal cortex, nucleus accumbens, and hippocampus. In the hippocampus, mRNA levels for all four genes were robustly elevated following social defeat in adolescence, whereas none were induced by defeat in adulthood. The relationship to coping style was also examined using adult reactive and proactive coping rats. Gene expression levels of reactive and proactive animals were similar in the prefrontal cortex and hippocampus. However, a trend toward a differential expression of BDNF and Arc mRNA in the nucleus accumbens was detected. BDNF mRNA was increased in the nucleus accumbens of proactive defeated animals, whereas the expression level in reactive defeated animals was comparable to control animals. The results demonstrate striking differences in immediate early gene expression in response to social defeat in adolescent and adult rats.

5-HT1A receptor activation reduces fear-related behavior following social defeat in Syrian hamsters

“…These findings are consistent with previous research in rats showing that two consecutive days of social defeat enhances Arc mRNA expression in the prefrontal cortex (Coppens et al 2011). We also found that 8-OH-DPAT treatment reduced Arc immunoreactivity in the PL cortex and led to a similar, albeit non-significant, reduction in the BLA and IL.…”

Adolescent social defeat alters N-methyl-d-aspartic acid receptor expression and impairs fear learning in adulthood

“…Reduced NMDA receptor expression in the infralimbic cortex adds to previous findings that the mPFC represents one of the major brain regions sensitive to the effects of adolescent social defeat [9, 13, 47]. Presuming that the reduced expression reflects decreased glutamatergic tone at NMDA receptors, it may represent an additional mechanism underlying changes to cognition and psychostimulant responses induced by adolescent defeat, which were previously attributed to decreased mPFC DA activity [17].…”

Isolation rearing attenuates social interaction-induced expression of immediate early gene protein products in the medial prefrontal cortex of male and female rats

“…These results suggest that activation of Arc in the mPFC may be involved in the normal social interactions with a novel conspecific, at least during late adolescence. The expression of Arc mRNA has been shown to increase in the mPFC of adolescent and adult male rats after social defeat stress [56]. However, Arc mRNA was not increased in the PL of rats after social interaction with a cagemate after a 24 hr separation [57].…”