Electroacupuncture improves learning and memory functions in a rat cerebral ischemia/reperfusion injury model through PI3K/Akt signaling pathway activation

Electroacupuncture has been widely used to treat cognitive impairment after cerebral ischemia,but the underlying mechanism has not yet been fully elucidated.Studies have shown that autophagy plays an important role in the formation and development of cognitive impairment,and the phosphoinositide 3-kinase(PI3K)/Akt signaling pathway plays an important role in autophagy regulation.To investigate the role played by the PI3K/Akt signaling pathway in the electroacupuncture treatment of cerebral ischemia/reperfusion rat models,we first established a rat model of cerebral ischemia/reperfusion through the occlusion of the middle cerebral artery using the suture method.Starting at 2 hours after modeling,electroacupuncture was delivered at the Shenting(GV24)and Baihui(GV20)acupoints,with a dilatational wave(1-20 Hz frequency,2 mA intensity,6 V peak voltage),for 30 minutes/day over 8 consecutive days.Our results showed that electroacupuncture reduced the infarct volume in a rat model of cerebral ischemia/reperfusion injury,increased the mRNA expression levels of the PI3K/Akt signaling pathwayrelated factors Beclin-1,mammalian target of rapamycin(mTOR),and PI3K,increased the protein expression levels of phosphorylated Akt,Beclin-1,PI3K,and mTOR in the ischemic cerebral cortex,and simultaneously reduced p53 mRNA and protein expression levels.In the Morris water maze test,the latency to find the hidden platform was significantly shortened among rats subjected to electroacupuncture stimulation compared with rats without electroacupuncture stimulation.In the spatial probe test,the number of times that a rat crossed the target quadrant was increased in rats subjected to electroacupuncture stimulation compared with rats without electroacupuncture stimulation.Electroacupuncture stimulation applied to the Shenting(GV24)and Baihui(GV20)acupoints activated the PI3K/Akt signaling pathway and improved rat learning and memory impairment.This study was approved by the Animal Ethics Committee of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine,China(approval No.8150150901)on March 10,2016.

Manic-depressive Psychosis as the Initial Symptom in Adult Siblings with Late-onset Combined Methylmalonic Aciduria and Homocystinemia, Cobalamin C Type

Methylmalonic aciduria （MMA） is an autosomal recessive disorder of cobalamin （cbl） metabolism. Cobalamin C （cblC） disease is the most common type of MMA and is characteristically concurrent with homocystinemia （HCY） due to impaired synthesis of two active forms of cbl, namely adenosylcobalamin （AdoCbl） and methylcobalamin （MeCbl）. The estimated worldwide incidence of MMA ranges between 1：48,000 and 1：250,000. Mutations of the MMA and HCY type C protein （MMACtfC） gene are responsible for cblC disease and were first identified by Lerner-Ellis et aL in 2006.By the year 2016, more than 82 different MMACHC gene mutations have been reported （http：// www.hgmd.cf.ac.uk/ac/index.php）. Among these mutations, c.609G〉A （p.W203X） was reported to be the most frequent cblC mutation in Chinese patients.