Brief maternal separation affects brain α1-adrenoceptors and apoptotic signaling in adult mice

Abstract

Exposure to adversity during early life is a risk factor for the development of different mood and psychiatric disorders, including depressive-like behaviors. Here, neonatal mice were temporarily but repeatedly (day 1 to day 13) separated from mothers and placed in a testing environment containing a layer of odorless clean bedding (CB). We assessed in adult animals the impact of this early experience on binding sites and mRNA expression of α1-adrenergic receptor subtypes, heat shock proteins (HSPs) and proapoptotic and antiapoptotic members of the Bcl-2 family proteins in different brain regions involved in processing of olfactory information and rewarding stimuli. We found that repeated exposure to CB experience produced anhedonic-like behavior in terms of reduced saccharin intake and α1-adrenoceptor downregulation in piriform and somatosensory cortices, hippocampus, amygdala and discrete thalamic nuclei. We also found a selective decrease of α1B-adrenoceptor binding sites in the cingulate cortex and hippocampus and an increase of hippocampal α1A and α1B receptor, but not of α1D-adrenoceptor, mRNA levels. Moreover, while a significant decrease of antiapoptotic heat shock proteins Hsp72 and Hsp90 was identified in the prefrontal cortex, a parallel increase of antiapoptotic members of Bcl-2 family proteins was found at the hippocampal level. Together, these data provide evidence that the early exposure to CB experience produced enduring downregulation of α1-adrenoceptors in the prefrontal-limbic forebrain/limbic midbrain network, which plays a key role in the processing of olfactory information and reaction to rewarding stimuli. Finally, these data show that CB experience can "prime" the hippocampal circuitry and promote the expression of antiapoptotic factors that can confer potential neuroprotection to subsequent adversity.