Alpha-lipoic acid improved motor function in MPTP-induced Parkinsonian mice by reducing neuroinflammation in the nigral and spinal cord

• DOI: 10.1016/j.neulet.2022.136669
• Publication Date: 2022-04-29T01:48:42Z
• Authors: Jian Zhang; Meng Wang; Yuan Zhao; Yidan Zhang; Ya Gao; Xiangjian Zhang; Guofeng Yang
• Keywords: Thioctic Acid; Tumor Necrosis Factor-alpha; Dopaminergic Neurons; NF-kappa B; Parkinson Disease; 01 natural sciences; 0104 chemical sciences; Mice, Inbred C57BL; Substantia Nigra; Disease Models, Animal; Mice; Spinal Cord; 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Neuroinflammatory Diseases; Animals; Microglia; 0101 mathematics

Parkinson's disease (PD) is a chronic neurodegenerative movement disorder, resulting in dopaminergic (DA) neuronal loss in the substantia nigra (SN) and injury of extranigral spinal cord neurons. This study was to investigate the effect of α-lipoic acid (ALA) on 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) induced neuroinflammation in the substantia nigra and spinal cord as well as motor function of the mice with PD. After MPTP induced mouse model with PD, the effect of ALA on motor defects was evaluated by measurement of fore and hind limb step length and suspension test. The effects of ALA on microglia in the SN and spinal cord of MPTP-induced Parkinsonian mice were detected by immunofluorescence. The effect of ALA on the protein level nuclear factor-κB (NF-κB) in MPTP-induced mice with PD were examined by Western blot. RT-qPCR was used to detect the effect of ALA on gene expression of tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS) in the SN and spinal cord of MPTP-induced mice. The behavioral results showed that ALA treatment significantly increased the step length and suspension time of MPTP-induced mice (P < 0.05). Immunofluorescence results showed that ALA significantly reduced MPTP-induced activation of microglia both in the SN and spinal cord (P < 0.05). Western blot and RT-qPCR showed that ALA significantly reduced the expression of NF-κB, TNF-α and iNOS in the nigra and spinal cord (P < 0.05). ALA can play a neuroprotective role through alleviating the activation of microglia, reducing neuroinflammation in the nigra and extranigra of mice induced by MPTP and therefore improving their motor dysfunction.