ALCAR Exerts Neuroprotective and Pro-Neurogenic Effects by Inhibition of Glial Activation and Oxidative Stress via Activation of the Wnt/β-Catenin Signaling in Parkinsonian Rats

摘要: Oxidative stress and neuroinflammation are known causative factors in progressive degeneration of dopaminergic (DAergic) neurons Parkinson’s disease (PD). Neural stem cells (NSCs) contribute maintaining brain plasticity; therefore, survival NSCs neuroblasts during neurodegenerative process becomes important replenishing the pool mature neuronal population. Acetyl-l-carnitine (ALCAR), present almost all body cells, increases endogenous antioxidants regulates bioenergetics. Currently, no information is available about putative mechanism neuroprotective effects ALCAR 6-hydroxydopamine (6-OHDA)-induced rat model PD-like phenotypes. Herein, we investigated effect on death/survival DAergic neurons, associates neuroprotection 6-OHDA-induced (100 mg/kg/day, intraperitoneal (i.p.)) treatment started 3 days prior to 6-OHDA lesioning continued for another 14 day post-lesioning. We found that pretreatment 6-OHDA-lesioned rats increased expression neurogenic Wnt pathway genes striatum substantia nigra pars compacta (SNpc) region. It suppressed glial cell activation, improved antioxidant status, NSC/neuroblast population rescued nigrostriatal pathway. decreased GSK-3β activation nuclear translocation β-catenin. Functional deficits were restored following as demonstrated by motor coordination rotational behaviour, confirming protection innervations lesioned striatum. These results indicate exerts through Wnt/β-catenin pathway, suggesting its therapeutic use treat diseases enhancing regenerative capacity.