The effect of TrkA signaling pathway on the expressions of TRPC1，TRPC3 in 6-hydroxydopamine lesioned rat treated by electroacupuncture

Abstract

Objective: We investigate the effect of TrkA signaling pathway on the expressions of transient receptor potential channel in 6-hydroxydopamine(6-OHDA) lesioned rat treated by electroacupuncture and to explore the role of trkA signaling pathway and TRP subfamily in the pathogenesis of Parkinson's disease (PD), which would reveals the mechanisms of electroacupuncture (EA) neuroprotective effect. Methods: The experimental models were established by unilateral injection of 6-OHDA into the left medial forebrain bundle (MFB).TrkA signaling pathway inhibitor K252a was infected into MFB through two small burr holes in the skull to block trkA signal.The change of TRPC1 and TRPC3 expressions was detected by use of immunohistochemistry and RT-PCR as well as TUNEL for cell apoptosis. Results: The expressions of TRPC1 and TRPC3 in the substantia nigra (SN) of the 6-OHDA lesioned rat were significantly reduced. Compared with PD model group, TRPC1 and TRPC3 expressions were significantly increased in the EA group. There was no statistically significance in TRPC1 and TRPC3 expressions between K252a and PD model groups ( P > 0.05). The number of apoptotic cells in SN increased 54.5% in the PD model rats, while positive apoptotic cells were significantly reduced in the EA group. There was no statistically significance in apoptotic cells between K252a and PD model groups ( P >0.05). Conclusion: TRPC1 and TRPC3 expressions downregulated in the SN of the 6-OHDA lesioned rat, which was accompanied by apoptosis increase in the SN. EA treatment could reverse this effect, and trkA signaling pathway inhibitors K252a can attenuate the neuroprotective effect of EA. It suggested that TRPC1 and TRPC3 may play an important role in the pathogenesis of PD, and certain TRPC subfamily expressions change may be associated with the pathogenesis of PD. Its expression might be subject to trkA signaling pathway, and this signal pathway may be the regulation target for EA neuroprotection.