The effects of unilateral 6-OHDA lesion in medial forebrain bundle on the motor, cognitive dysfunctions and vulnerability of different striatal interneuron types in rats

Abstract

In this study, the motor deficit, cognition impairment and the vulnerability of different striatal interneurons to the 6-hydroxydopamine (6-OHDA)-induced excitotoxicity in unilateral medial forebrain bundle (MFB) lesion rats were analyzed by employing behavioral test, immunohistochemistry and Western blot methods. The apomorphine-induced rotation after MFB lesion was used as a valid criterion of motor deficit. The 6-OHDA damaged rats had limb rigidity with longer hang time compared to the controls in the grip strength test. Cognitive and mnemonic deficits of rats with unilateral MFB lesion were observed by the water maze task. The MFB lesion resulted in a significant loss of tyrosine hydroxylase (TH)+ cells in the contralateral striatum or substantia nigra. After dopaminergic depletion, the numbers of calretinin (Cr)+ and choline acetyltransferase (ChAT)+ interneurons were notably reduced while these of neuropeptide Y (NPY)+ were markedly increased in the striatum. No noticeable change in the number of parvalbumin (Parv)+ interneurons was found in 6-OHDA rats. In addition, the fiber densities for each individual interneuron were increased after 6-OHDA treatment, especially for the fiber densities of Parv+ and Cr+ interneurons. The Western blot analysis further confirmed the results described above. In conclusion, the MFB lesion model is suitable to mimic Parkinson's disease (PD), and our results are helpful for further understanding the underlying mechanism and the specific functions of various striatal interneurons in the pathological process of PD.