Modulation of connexin 36 expression in basal ganglia and motor cortex in rat model of Parkinson's disease

Abstract

Objective To observe the expression of connexin 36 (Cx36) in the striatum and motor cortex of rat model of Parkinson's disease (PD) in order to explore whether gap junction is involved in the pathogenesis of the cortex-basal ganglia circuit disturbances in PD. Methods Hemi-parkinsonian rat model was produced by stereotaxically injecting 6-hydroxydopamine (6-OHDA) to right medial forebrain bundle (MFB). Immunohistochemical staining and Western blotting analysis were used to observe the expression changes of Cx36 in the striatum and motor cortex. Double immunofluorescence labeling was used to analyze the expression of Cx36 in enkephalin (ENK) positive medium spiny neurons and Parvalbumin (PV) positive interneurons in the striatum. Results Immunohistochemical staining showed Cx36 expression was elevated in the right striatum as well as right motor cortex of PD group compared with normal control group (t = 2.474, P = 0.048; t = 2.614, P = 0.040). Double immunofluorescence labeling staining revealed that ENK-positive striatum neurons were elevated (t = 3.987, P = 0.007) and Cx36 expression was increased in ENK-positive striatum neurons (t = 3.271, P = 0.017) in PD group compared with normal control group. While PV-positive interneurons decreased (t = 2.777, P = 0.032) and Cx36 expression was down-regulated in PV-positive interneurons (t = 2.624, P = 0.039) compared with the normal control group. Western blotting indicated that the 6-OHDA lesion induced a significant upregulation of Cx36 to (119.31 ± 8.92)% in comparison with the normal group [(104.05 ± 3.82)%] in right striatum (t = 3.516, P = 0.024). In right motor cortex Cx36 increased to (138.20 ± 17.88)% , induced a significant upregulation of Cx36 in the right motor cortex in comparison with the normal control group [(105.27 ± 2.82)%; t = 4.068, P = 0.015]. Conclusion The Cx36 expression was generally increased in the striatum and motor cortex of PD rat model, with upregulation in ENK-positive striatum neurons but downregulation in PV-positive interneurons, suggesting that gap junction dysfunction may play an important role in the disturbance of cortex-basal ganglia pathway in PD.