Rho-inhibition and neuroprotective effect on rotenone-treated dopaminergic neurons in vitro

Abstract

Mesencephalic cell cultures are a good model to study the vulnerability of dopaminergic neurons and reproduce, in vitro, experimental models of Parkinson's disease. Rotenone associated as an environmental neurotoxin related to PD, is able to provoke dopaminergic neuron degeneration by inhibiting complex I of the mitochondrial respiratory chain and by inducing accumulation of α-synuclein. Recently, rotenone has been described to activate RhoA, a GTPase protein. In the present study we evaluated a possible neuroprotective effect of Rho-inhibitor molecules on rotenone-damaged dopaminergic (DA) neurons obtained from mouse primary mesencephalic cell culture. Our results showed that Clostridium Botulinum C3 toxin (C3) and simvastatin, as RhoA inhibitors, were able to protect DA neurons from rotenone damages. In fact, pretreatment with C3 or simvastatin significantly prevented the reduction of [³H]dopamine uptake, neurites injury and the expression patterns of proteins like α-syn, actin and connexin 43.

Keywords: Connexin 43; Mesencephalic cell culture; RhoA; RhoA inhibitors; Rotenone; α-Synuclein.