First evidence of protective effects on stroke recovery and post-stroke depression induced by sortilin-derived peptides.

摘要: Abstract Post-stroke depression (PSD) is the most common mood disorder following stroke with high relevance for outcome and survival of patients. The TREK-1 channel represents a crucial target in pathogenesis depression. Spadin its short analog mini-spadin were reported to display potent antidepressant properties. We investigated therapeutic effects mouse model focal ischemia PSD. To activate induce neuroprotection single low dose (0.03 μg/kg) was intraperitoneally injected 30  min after onset ischemia, once day during 7 days post-ischemia. Then, inhibit effect, peptide at higher concentration (3 μg/kg) 4 days/week until sacrifice animals. Electrophysiological studies showed that had biphasic action on TREK-1. At doses, activity increased whereas doses it inhibited. Mini-spadin prevented loss body weight delayed dopaminergic degeneration substantia nigra improved motor cognitive ischemia-induced deficits. Moreover, PSD analyzed Forced Swim (FST) Novelty Suppressed Feeding (NSF) tests. Finally, enhanced neurogenesis synaptogenesis contributed beneficial against This work reveals first evidence modulation channels early chronic phases as well stimulation brain plasticity by could play key role protective deleterious consequences such