Ifenprodil Intracerebrally Offers Neuroprotection against 6-OHDA-Induced Toxicity in SD-Rats via Enhancing Autophagy Function

The progressive decline of dopamine neurons in the substantia nigra is the main pathogenic change in Parkinson’s disease (PD). Studies have found that excessive excitement of glutamatergic neurons causes intracellular calcium overload and induces autophagy impairment, which is one of the main mechanisms of dopamine neuron damage. The neuroprotective effect of Ifenprodil against 6-OHDA-injured mice was studied in this study. Ifenprodil was administered intraperitoneally (i.p.) or intracerebrally to rats who had a nigral-striatum pathway lesioned by 6-OHDA stereotactic brain injection. The ability to move was evaluated. The survival of dopamine neurons in the nigral was determined using HE staining, while TH-positive expression was measured using immunohistochemistry. Western Blot was used to examine the expression of CaM protein and light chain 3 (LC3), Beclin-1, BNIP3LNix, and p62. The results revealed that Ifenprodil improves motor function in 6-OHDA rats, and intracerebral injection is more effective than systemic administration. The same results also found in HE and IHC. Ifenprodil enhanced LC3II, BNIP3LNix, and Beclin-1 while decreasing p62, p-CaMKII, and β-Ca expression. In addition, Ifenprodil reduced the activation of microglia caused by 6-OHDA. Overall, the findings imply that Ifenprodil intracerebrally may protect against Parkinson’s disease via modulating autophagy-related proteins during 6-OHDA-induced toxicity.