| Autor: |
Jia Y; Department of Physiology and Pathophysiology, School of Basic Medicine, Qingdao University, 308 Ningxia Road, Qingdao 266071, China., Li J; Department of Nutrition and Food Hygiene, School of Public Health, Qingdao University, 308 Ningxia Road, Qingdao 266071, China., Wang Y; Department of Nutrition and Food Hygiene, School of Public Health, Qingdao University, 308 Ningxia Road, Qingdao 266071, China., Ma Y; Department of Nutrition and Food Hygiene, School of Public Health, Qingdao University, 308 Ningxia Road, Qingdao 266071, China., Chen L; Department of Physiology and Pathophysiology, School of Basic Medicine, Qingdao University, 308 Ningxia Road, Qingdao 266071, China., Zhang H; Department of Nutrition and Food Hygiene, School of Public Health, Qingdao University, 308 Ningxia Road, Qingdao 266071, China., Xue M; Department of Biochemistry and Molecular Biology, School of Basic Medicine, Qingdao University, 308 Ningxia Road, Qingdao 266071, China., Liang H; Department of Nutrition and Food Hygiene, School of Public Health, Qingdao University, 308 Ningxia Road, Qingdao 266071, China. |
| Abstrakt: |
Parkinson's disease (PD) is marked by the degeneration of dopaminergic neurons of the substantia nigra (SN), with neuroinflammation and mitochondrial dysfunction being key contributors. The neuroprotective potential of folic acid (FA) in the dopaminergic system of PD was assessed in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model. MPTP (20 mg/kg of body weight) was administered to C57BL/6J mice to simulate PD symptoms followed by FA treatment (5 mg/kg of body weight). Behavioral tests, pole, rotarod, and open-field tests, evaluated motor function, while immunohistochemistry, ELISA, RT-qPCR, and Western blotting quantified neuroinflammation, oxidative stress markers, and mitochondrial function. FA supplementation considerably improved motor performance, reduced homocysteine levels and mitigated oxidative damage in the SN. The FA-attenuated activation of the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome lessened glial cell activity and reduced neuroinflammation. At the molecular level, FA reduced DNA damage, downregulated phosphorylated p53, and induced the expression of peroxisome proliferator-activated receptor α coactivator 1α (PGC-1α), enhancing mitochondrial function. Therefore, FA exerts neuroprotection in MPTP-induced PD by inhibiting neuroinflammation via NLRP3 inflammasome suppression and promoting mitochondrial integrity through the p53-PGC-1α pathway. Notable limitations of our study include its reliance on a single animal model and the incompletely elucidated mechanisms underlying the impact of FA on mitochondrial dynamics. Future investigations will explore the clinical utility of FA and its molecular mechanisms, further advancing it as a potential therapeutic for managing and delaying the progression of PD. |
