Neuroprotective Action of Agmatine in Rotenone-Induced Model of Parkinson's Disease: Role of BDNF/CREB and ERK Pathway

Abstract

Numerous studies have investigated the role of agmatine in the central nervous system and indicated neuroprotective properties. In addition to its potent antioxidant effects, agmatine is an endogenous neuromodulator and has wide spectrum molecular actions on different receptor subtypes (NMDA, Imidazoline 1-2, alpha-2 adrenoreceptor, 5-HT2a, 5-HT3) and cellular signaling pathways (MAPK, PKA, NO, BDNF). Although the neuroprotective effects of agmatine demonstrated in experimental Parkinson's disease model, the effects of agmatine with the aspect of neuroplasticity and possible signaling mechanisms behind agmatine actions have not been investigated. Herein, in this study, we investigated the role of the of agmatine on rotenone-induced Parkinson's disease model. Agmatine at the dose of 100 mg/kg i.p., was mitigated oxidative damage and alleviated motor impairments which were the results of the rotenone insult. Additionally, agmatine decreased neuronal loss, tyrosine hydroxylase immunoreactivity and increased cREB, BDNF and ERK1/2 expression in the striatum, which are crucial neuroplasticity elements of striatal integrity. Taken together, the present study expands the knowledge of molecular mechanisms behind neuroprotective actions of agmatine in Parkinson's disease, and as far as we have known, this is the first study to delineate agmatine treated activation of cellular pathways which are important elements in neuronal cell survival.