Differential gene expression of components of the hypothalamic-pituitary adrenal axis signalling in juvenile and adult mice

Stressful life events are known to correlate with an increase in the risk of depression in humans. In depressed adults, there is overactivity of the hypothalamic-pituitary-adrenal (HPA) axis in up to 50% of patients, who show both an increase in cortisol levels as well as reduced negative feedback inhibition. Conversely, this increase in cortisol is not always reported in adolescent depression (Kaufman et al. 2001. Biol. Psychiat. 49(12): 980-1001). Reduced expression of glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) in the hypothalamus of depressed adults has been reported (Pariante and Lightman, 2008, Trends Neurosci. 31(9) 464-468). Similar reductions in GR and MR expression have been shown in mice following chronic stress. In both cases this reduced expression corresponds with impaired negative feedback inhibition of the HPA axis seen by non-suppression of glucocorticoid release in the dexamethasone suppression test. However, less is known about the expression of key components of HPA signalling in juvenile mice and whether this changes in response to stress. Here, we have determined gene expression patterns of components of HPA signalling in adult (9-10 weeks old) and juvenile (4-5 weeks old) BALB/cAnNCrl mice (Charles River, UK) both at baseline and following a repeated stress procedure. Expression of GR, MR, CRH, CRHR1, CHRH2, AVP and V1b were determined in the hypothalamus, hippocampus, prefrontal cortex and pituitary gland of both adult and juvenile mice using quantitative RT-PCR. Blood samples were taken from the tail vein at baseline and following stress, and neuroendocrine function was determined using ELISAs. In control, non-stressed animals, juvenile mice showed increased AVP expression, and decreased CRHR1 expression, in the hypothalamus, compared with adult mice. These data suggest there may be differences in HPA function between adult and juvenile mice that may have repercussions for stress-responsiveness and the development of depression-like behaviours.