Tianjin Medical Journal ›› 2021, Vol. 49 ›› Issue (5): 476-482.doi: 10.11958/20203189

• Experimental Study • Previous Articles     Next Articles

Effects of low-dose ketamine on neurological function and inflammation factors of MPTP induced Parkinson's disease mice

SONG Jun-jie, FAN Jun-chao△, CHEN Ying, CHEN Yong   

  • Received:2020-11-18 Revised:2021-02-03 Published:2021-05-15 Online:2021-05-25

Abstract:

Abstract: Objective To investigate the effects of low-dose ketamine on the neurological function and neuroinflammation of MPTP induced Parkinson's disease (PD) mice. Methods Fifty C57BL/6 mice were divided into the NC group, PD group, PD+Keta-L group, PD+Keta-M group and PD+Keta-H group according to random number table method, with 10 mice in each group. PD+Keta-L, PD+Keta-M and PD+Keta-H groups were administered intraperitoneally with 25, 50 and 75 mg/kg ketamine, respectively, once a day for 2 d. PD group, PD+Keta-L, PD+Keta-M and PD+Keta-H groups were  intraperitoneally injected with MPTP 20 mg/kg once a day for 20 days to establish PD mouse models. The gait and modified Neurological Severity Scores (MNSS) were observed in each group. The brain tissues were collected, and HE staining was used to observe the morphological changes of brain nerve cells. The expression of tyrosine hydroxylase (TH) in nerve cells was detected by immunohistochemistry, and the apoptosis of nerve cells was detected by TUNEL assay. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1β were determined by ELISA. The protein levels of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and nuclear factor (NF) -κB p65 in brain tissues were determined by Western blot assay. Results Compared with NC group, the abnormal gaits, the MNSS score, the apoptosis of nerve cells and levels of TNF-α, IL-6 and IL-1β were increased in PD group, and the proportion of TH positive cells was decreased (P<0.05). Compared with PD group, the abnormal gaits was improved, the MNSS score, nerve cell apoptosis rate, TNF-α, IL-6 and IL-1β levels were decreased, , and the proportion of TH positive cells was increased in PD+ Keta-L group (P<0.05). There were no significant differences in these indices between PD+Keta-M group, PD+Keta-L group and PD group (P>0.05). The expressions of TLR4, NF-κB p65 and MyD88 were significantly higher in the PD group than those in the NC group (P<0.05). Compared with the PD group, the expressions of TLR4, NF-κB p65 and MyD88 were significantly decreased in the PD+Keta-L group (P<0.05). TLR4 and MyD88 were decreased only in the PD+ Keta-M group (P<0.05), and there were no significant changes in these proteins between PD+Keta-H group and PD group (P>0.05). Conclusion The low-dose ketamine has certain neuroprotective effect on PD mice.

Key words: Parkinson disease, ketamine, tyrosine 3-monooxygenase, apoptosis, neuroprotection, neurological function, neuroinflammation