title: Electroacupuncture ameliorates memory impairments by enhancing oligodendrocyte regeneration in a mouse model of prolonged cerebral hypoperfusion.
abstract: We modeled prolonged cerebral hypoperfusion in mice using bilateral common carotid artery stenosis (BCAS) and electroacupuncture (EA) stimulation was applied at two acupoints, Baihui (GV20) and Dazhui (GV14). In behavioral tests of memory, BCAS produced impairments in spatial and short-term memory in mice that were attenuated by therapeutic EA stimulation. Therapeutic use of EA in BCAS also enhanced oligodendrocyte (OL) differentiation from oligodendrocyte precursor cells (OPCs), in association with white matter improvements in the corpus callosum (CC). In PCR analyses of growth factor gene expression, significant positive changes in 3 genes were observed following EA stimulation in BCAS, and here we highlight alterations in neurotrophin-4/5 (NT4/5). We confirmed EA-mediated positive changes in the expression of NT4/5 and its receptor, tyrosine receptor kinase B (TrkB). Treatment of naïve and BCAS + EA animals with a selective TrkB antagonist, ANA-12, produced losses of myelin and cognitive function that were ameliorated by EA therapy. Moreover, following BCAS we observed an EA-dependent increase in phospho-activated CREB (a downstream mediator of NT4/5-TrkB signaling) in OPCs and OLs of the CC. Our results suggest that EA stimulation promotes the recovery of memory function following white matter injury via a mechanism that promotes oligodendrocyte regeneration and involves NT4/5-TrkB signaling.
authors.affiliation: Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan 50612, Korea.|Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan 50612, Korea.
authors.forename: Sung Min
authors.initials: SM
authors.lastname: Ahn
authors.affiliation: Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan 50612, Korea.
authors.forename: Yu Ri
authors.initials: YR
authors.lastname: Kim
authors.affiliation: Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan 50612, Korea.|Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan 50612, Korea.
authors.forename: Ha Neui
authors.initials: HN
authors.lastname: Kim
authors.affiliation: Department of Rehabilitation Medicine, School of Medicine, Pusan National University, Yangsan 50612, Korea.
authors.forename: Yong-Il
authors.initials: YI
authors.lastname: Shin
authors.affiliation: Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan 50612, Korea.|Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan 50612, Korea.|Division of Meridian and Structural Medicine, School of Korean Medicine, Pusan National University, Yangsan 50612, Korea.
authors.forename: Hwa Kyoung
authors.initials: HK
authors.lastname: Shin
authors.affiliation: Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan 50612, Korea.|Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan 50612, Korea.|Division of Meridian and Structural Medicine, School of Korean Medicine, Pusan National University, Yangsan 50612, Korea.
authors.forename: Byung Tae
authors.initials: BT
authors.lastname: Choi
mesh_terms: D015669:Acupuncture Points; D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000473:pathology*; D002545:Brain Ischemia / Q000628:therapy*; D002454:Cell Differentiation; D003337:Corpus Callosum / Q000378:metabolism; D004195:Disease Models, Animal; D015671:Electroacupuncture; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D008297:Male; D008569:Memory Disorders / Q000628:therapy*; D008570:Memory, Short-Term; D051379:Mice; D008810:Mice, Inbred C57BL; D009414:Nerve Growth Factors / Q000378:metabolism; D009416:Nerve Regeneration; D009836:Oligodendroglia / Q000166:cytology / Q000502:physiology*; D010477:Perfusion; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D009414:Nerve Growth Factors; C073922:neurotrophin 4