Effect of electroacupuncture of "Fengfu" (GV16) and "Taichong" (LR3) on EIF2α-ATF4-GRP78/Bip signaling in substantia nigra of rats with Parkinson's disease

Abstract

To observe the effect of electroacupuncture (EA) on expression of eukaryotic initiation factor 2α (EIF2α), activating transcription factor 4 (ATF4), glucose regulator protein-78 / immunoglobulin heavy-chain-binding protein (GRP78/Bip) in the substantia nigra (SN) in rats with Parkinson's disease (PD), so as to explore its mechanism underlying improvement of PD. Forty-eight male SD rats were randomly divided into control, sham-operation, model and EA groups (n=12 in each group). The PD model was established by 28-day consecutive subcutaneous injection of rotenone (1 mg/kg dissolved in dimethyl sulfoxide and normal saline) at the back shoulder. EA (2 Hz, 1 mA) was applied to "Fengfu" (GV16) and "Taichong" (LR3) for 30 min, once daily for 2 weeks. The behavio-ral changes of rats in each group were measured and scored at 28th day and 44th day, respectively. The expressions of tyrosine hydroxylase (TH) and α-synuclein (α-syn) in the SN were observed by immunohistochemistry, and the expressions of EIF2α, ATF4 and GRP78/Bip were detected by Western blot. Following modeling and compared with the control and sham-operation groups, the behavioral scores of rats in the model group were elevated (P<0.01), which were significantly decreased by EA intervention (P<0.01). The expression of TH decreased whereas the α-syn, EIF2α, ATF4 and GRP78/Bip increased in the rats of model group, and EA intervention reversed these changes (all P<0.01). EA at GV16 and LR3 can improve PD rats' behavioral changes, which is probably related with its effects in up-regulating the expression of TH in the SN and down-regulating the expression of α-syn and EIF2α-ATF4-GRP78/Bip signaling.