Early life stress blunts time-of-day-specific autonomic function in adult male mice

Early life stress (ELS) is an independent risk factor for cardiovascular disease, including hypertension. The current study was designed to test the hypothesis that exposure to ELS disrupts autonomic function in adult mice at baseline and in response to an acute behavioral stressor. Using the mouse model of ELS, maternal separation with early weaning (MSEW), we determined the effects of ELS on heart rate (HR), blood pressure (BP), locomotor activity (LMA), HR variability (HRV), and spontaneous baroreceptor sensitivity (sBRS) in adult male mice. Under basal conditions, normally reared (NR) and MSEW mice had similar HR, BP, LMA, and sBRS when characterized at different phases of the circadian cycle. Spectral analysis of HRV indicated that MSEW mice had significantly lower total power and low-frequency (LF) power during the inactive or light period, as well as a loss of diurnal rhythm of LF power compared with NR mice. When subjected to an acute behavioral stress, cage switch stress (CSS), NR and MSEW mice showed similar changes in HR, BP, and LMA. Frequency domain analysis of HRV indicated that total, LF, and high frequency power during CSS and recovery from CSS were all significantly decreased in MSEW mice compared with NR mice. Taken together, these findings indicate that exposure to ELS in mice disrupts autonomic function basally and in response to an acute behavioral stress in a time-of-day dependent manner.NEW & NOTEWORTHY Early life stress is a known risk factor for cardiovascular disease in adulthood. The current study provides evidence for impaired regulation of the autonomic nervous system in adult mice after being exposed to maternal separation with early weaning, an established model of neglect.