Aging is associated with lower neuroactive steroids and worsened outcomes following cerebral ischemia in male mice

Endocrinology. 2022 Oct 28:bqac183. doi: 10.1210/endocr/bqac183. Online ahead of print.ABSTRACTIschemic stroke is a leading cause of disability and death and aging is the main non-modifiable risk factor. Following ischemia, neuroactive steroids have been shown to play a key role in cerebroprotection. Thus, brain steroid concentrations at the time of injury as well as their regulation after stroke are key factors to consider. Here, we investigated the effects of age and cerebral ischemia on steroid levels, behavioral outcomes and neuronal degeneration in 3-month-old and 18-month-old C57BL/6JRj male mice. Ischemia was induced by middle cerebral artery occlusion for 1 hour followed by reperfusion (MCAO/R) and analyzes were performed at 6 h post-MCAO. Extended steroid profiles established by gas chromatography coupled with tandem mass spectrometry revealed that: i) brain and plasma concentrations of the main 5α-reduced metabolites of progesterone, 11-deoxycorticosterone, and corticosterone were lower in old than in young mice ii) after MCAO/R, brain concentrations of progesterone, 5α-dihydroprogesterone, and corticosterone increased in young mice and iii) after MCAO/R, brain concentrations of 5α-reduced metabolites of progesterone, 3α5α-tetrahydrodeoxycorticosterone and 3β5α-tetrahydrodeoxycorticosterone were lower in old than in young mice. Following ischemia, old mice showed increased sensorimotor deficits and more degenerating neurons in the striatum than young mice. Al...
Source: Endocrinology - Category: Endocrinology Authors: Source Type: research