Neuroprotective effect of Eugenia uniflora against intranasal MPTP-induced memory impairments in rats: The involvement of pro-BDNF/p75(NTR) pathway

Parkinson's disease is a multisystemic neurodegenerative disorder that includes motor and non-motor symptoms, and common symptoms include memory loss and learning difficulties. Thus, we investigated the neuroprotective potential of a hydroalcoholic extract of Brazilian purple cherry (Eugenia uniflora) (HAE-BC) on memory impairments induced by intranasal 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration in rats and the involvement of hippocampal BDNF/TrkB/p75NTR pathway in its effects. Adult male Wistar rats were exposed to MPTP (1 mg/nostril) or vehicle. Twenty-four hours later, the HAE-BC treatments began at doses of 300 or 2000 mg/kg/day or vehicle for 14 days. From 7 days after the MPTP induction, the animals were subjected to behavioral tests to evaluate several cognitive paradigms. HAE-BC treatments, at both doses, blocked the MPTP-caused disruption in the social recognition memory, short- and long-term object recognition memories, and working memory. Furthermore, MPTP-induced motor deficit linked to striatal tyrosine hydroxylase levels decreased, which was blocked by HAE-BC. Our findings demonstrated that HAE-BC blocked the MPTP-induced increase in the hippocampal pro-BDNF, TrkB.t1, and p75NTR levels. The pro-BDNF/p75NTR interaction negatively regulates synaptic transmission and plasticity, and the neuroprotective effect of HAE-BC was related, at least partly, to the modulation of this hippocampal signaling pathway. Thus, our study reports the first evidence of the potential therapeutic of E. uniflora in a Parkinson's disease model in rodents.