Amelioration of rotenone-induced Parkinson's disease; comparing therapeutic role of erythropoietin versus low-level laser activation of mesenchymal stem cells (an in-vivo and in-vitro study)

Abstract

ABSTRACT Parkinson's disease (PD), the second common neurodegenerative disease, is characterized by the loss of the dopaminergic neurons in the substantia nigra (SN). Because of L-dopa's side effects, new therapeutic methods were considered such as stem cells for PD treatment. The major challenge facing stem cell therapy following transplantations is their peripheral sequestration and decreased survival. Thus, the ability of erythropoietin (EPO) and low-level laser therapy (LLLT) to enhance mesenchymal stem cell (MSC) proliferation and therapeutic efficiency for alleviating rotenone-induced PD was investigated. Therefore, we compared the influence of stem cell preconditioning with erythropoietin versus LLLT on MSCs’ homing ability and the chances of survival. Forty-eight male Swiss mice were included in the in vivo protocol and ten in the in vitro work. The mice in the in vivo study were divided randomly into six groups (8 in each); group I; control group and group II; induced PD (untreated) group, group III; L-dopa, group IV; MSCs, group V; EPO-activated MSCs and group VI; laser-activated MSCs. Treatment with MSCs (either preconditioned or not) improved these neurological features by restoring the normal balance between glutamate and GABA neurotransmitters, and dopamine as well as increased tyrosine hydroxylase levels. Stem cell therapy decreased oxidative stress, miRNA-155 levels, enhanced neuronal architecture in SN, and decreased the number of apoptotic cells. LLLT enhanced MSC expression of integrin β1 which was reflected in the homing of PKH26-labelled MSCs into corpus striatum and SN. Thus, the optimum results were achieved with laser-activated MSCs.