Signal Transduction Pathways of Acupuncture for Treating Some Nervous System Diseases

Table 7

Signal transduction pathways of acupuncture in treating Parkinson’s disease.

Subjects	Location	Acupoint	Intervention	Time of intervention	Signal pathway	Main results	Author, reference
Male SD rats, rotenone injection	substantia nigra	GV16, LR3	EA, 1mA, 2Hz	20min, QD for 14 days	inactivation of p38-MAPK pathway	elevation of tyrosine hydroxylase-positive neuron; depression of phosphorylated p38-MAPK, COX-2; decrease neuroinflammation	Wang SJ, et al. 2013[158]
Male SD rats, rotenone injection	substantia nigra	GV16, LR3	EA, 2mA, 2Hz	20min, QD for 14 days	inactivation of ERK 1/2 pathway	elevation of tyrosine hydroxylase protein; depression of p-ERK 1/2, TNF-α, IL-1β; decrease neuroinflammation	Wang SJ, et al. 2014[159]
Male C57BL/6 mice, MPTP injection	substantia nigra, striatum	GB34	MA, 2Hz for 15sec	QD for 7 days	activation of PI3K/Akt pathway	elevation of pAkt; prevents MPTP-induced dopaminergic neuron degeneration	Kim SN, et al. 2011[160]
Male C57BL/6 mice, MPTP injection	substantia nigra pars compacta, striatum	GB34	MA, 2Hz for 15sec	QD for 12 days	activation of PI3K/Akt pathway	elevation of dopamine; depression of dopamine- and cAMP-regulated phosphoprotein of 32 kDa, Fos; increase dopamine turnover rate	Kim SN, et al. 2011[161]
Male, C57BL6 mice (MPTP intraperitoneal injection) and SD rats (Sigma-Aldrich injection into substantia nigra)	substantia nigra	GB34, LR3	EA, 1mA, 50Hz	QD for 5(mice)/7(rats) days	activation of Akt pathway	elevation of BDNF, Bcl-2, tyrosine hydroxylase; regulation of cell cycle	Lin JG, et al. 2017[162]
Imprinting control region mouse pups, systemic 6- hydroxydopamine injection	hippocampus	KI3	EA, 1mA, 2Hz	15min, QD, 5 days/wk for 6wks	inactivation of pPKA/pPKC/CaMKIIα signaling pathways	depression of pNR1, pNR2B, pPKA, pPKC, pCaMKIIα, pERK, pCREB; reduce neuronal excitotoxicity	Lu KW, et al. 2017[163]
Male C57BL/6 mice, MPTP injection	substantia nigra par compacta	GB34	MA, 2Hz for 15sec every 5min	10min, QD for 7 days	m-TOR independent pathway	depression of α-synuclein; induces autophagic clearance of α-syn, dopaminergic neurons protection	Tian T, et al. 2016[164]
Male C57BL/6 mice, MPTP injection	substantia nigra, striatum	GB34, GB39	EA, 1mA, 100Hz	20min, QD for 12 days	regulation of glyoxalase system	elevation of tyrosine hydroxylase-positive neurons, cytochrome c oxidase subunit Vb; depression of cytosolic malate dehydrogenase, munc18-1, hydroxyacylglutathione hydrolase; anti-oxidative effect	Kim ST, et al. 2010[165]
Male C57BL/6 mice, MPTP injection	midbrain, striatum	ST36, SP6	EA, 1-1.4mA, 100Hz	30min, QD for 12 days, except day 7	activation of Nrf2-ARE pathway	elevation of tyrosine hydroxylase, ARE-driven reporter gene, NQO1, HO-1; depression of ionized calcium-binding adaptor molecule 1, TNF-α, IL-6, IL-1β; anti-oxidative effect	Lv E, et al. 2015[166]
GFAP-tTA/tetO-α-syn double transgenic mice	midbrain, striatum	ST36, SP6	EA, 1-1.2mA, 100Hz	30min, QD for 28 days	activation of Nrf2-ARE pathway	elevation of Nrf2, HO-1, glutamate-cysteine ligase modifier subunits; depression of α-syn; decrease astrogliosis and neuroinflammation	Deng J, et al. 2015[167]
Male C57BL/6 mice, MPTP injection	striatum, substantia nigra	GB34	MA, 2Hz, 15sec	QD for 12 days	activation of p53 signaling pathways	elevation of p53; dopaminergic neuron protection	Park JY, et al. 2015[168]

Abbreviations
Akt: protein kinase B; ARE: antioxidant response element; CaMK: Ca2+/calmodulin-dependent protein kinase; cAMP: cyclic adenosine monophosphate; COX: cyclooxygenase; CREB: phosphorylated cyclic AMP response element-binding protein; EA: electroacupuncture; ERK: extracellular signal-regulated kinase; HO-1: heme oxygenase-1; IL: interleukin; MA: manual acupuncture; MPTP: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; mTOR: mammalian target of rapamycin; NQO1: nicotinamide adenine dinucleotide phosphate quinone oxidoreductase; Nrf2: nuclear factor erythroid 2-related factor 2; p38 MAPKs: p38 mitogen-activated protein kinases; PI3K: phosphatidylinositol-4,5-bisphosphate 3-kinase; PKA: protein kinase A; PKC: protein kinase C; pNR: phosphorylated N-methyl-D-aspartate receptor; QD: daily; SD rat: Sprague Dawley rat; TNF-α: tumor necrosis factor-alpha.