01-08-2023
Chronic long-term exposure by all GABAA receptor agonists, e.g., benzodiazepines, barbiturates and alcohol, give permanent memory and learning impairment. The sex-steroid medroxyprogesterone, given as postmenopausal hormone therapy, double the dementia frequency in 5 years. The neuroactive steroid allopregnanolone inhibits learning in rat studies. Chronically high cortisol and GABA-steroid levels give irreversible cognitive damages.
Indeed, and consistent with a greater allostatic load model (McEwen, 1998), it has been suggested that the neurosteroid depletion consistently documented in patients with depression is likely associated with chronic stress (Reddy, 2003). When compared with non-depressed controls, depressed patients have lower plasma and CSF concentrations of allopregnanolone (Romeo et al., 1998; Uzunova et al., 1998; Strohle et al., 1999, 2000; Nappi et al., 2001; Eser et al., 2006, Uzunova et al., 2006) but higher allotetrahydroDOC concentrations (Strohle et al., 1999, 2000), which may reflect differential alteration in the biosynthesis of deoxycorticosterone or its metabolites in depression (Strohle et al., 1999, 2000).
Rapid actions by corticosterone would allow the brain to change its function within minutes after stress-induced elevations of corticosteroid levels, in addition to responding later through gene-mediated signaling pathways.
It is well established that L-NAME, a generic NOS inhibitor, stimulates neurogenesis in the dentate gyrus of the adult rat and corticosterone reduces it.
Участник:CopperKettle/Планы/Минипроект Механизмы Стресса.
