Acetyl-l-Carnitine via Upegulating Dopamine D1 Receptor and Attenuating Microglial Activation Prevents Neuronal Loss and Improves Memory Functions in Parkinsonian Rats

摘要: Parkinson's disease is accompanied by nonmotor symptoms including cognitive impairment, which precede the onset of motor in patients and are regulated dopamine (DA) receptors mesocorticolimbic pathway. The relative contribution DA astrocytic glutamate transporter (GLT-1) functions largely unexplored. Similarly, whether microglia-derived increased immune response affects neuronal survival not yet understood. We have investigated effect acetyl-L-carnitine (ALCAR) on its possible underlying mechanism action 6-hydroxydopamine (6-OHDA)-induced hemiparkinsonian rats. ALCAR treatment 6-OHDA-lesioned rats improved memory as confirmed decreased latency time path length Morris water maze test. further enhanced D1 receptor levels without altering D2 hippocampus prefrontal cortex (PFC) regions, suggesting that preferentially involved regulation functions. attenuated microglial activation release inflammatory mediators through balancing proinflammatory anti-inflammatory cytokines, subsequently mature neurons CA1, CA3, PFC regions also glutathione (GSH) content, while decreasing oxidative stress indices, inducible nitrogen oxide synthase (iNOS) levels, astrogliosis resulting upregulation GLT-1 levels. Additionally, prevented loss dopaminergic (DAergic) ventral tagmental area (VTA)/substantia nigra pars compacta (SNpc) rats, thus maintaining integrity nigrostriatal Together, these results demonstrate ameliorates neurodegeneration deficits, hence therapeutic potential neurodegenerative diseases.