title: Upregulation of TrkB by forskolin facilitated survival of MSC and functional recovery of memory deficient model rats.
abstract: Mesenchymal stem cells (MSCs) are effective vectors in delivering a gene of interest into degenerating brain. In ex vivo gene therapy, viability of transplanted MSCs is correlated with the extent of functional recovery. It has been reported that BDNF facilitates survival of MSCs but dividing MSCs do not express the BDNF receptor, TrkB. In this study, we found that the expression of TrkB is upregulated in human MSCs by the addition of forskolin (Fsk), an activator of adenylyl cyclase. To increase survival rate of MSCs and their secretion of tropic factors that enhance regeneration of endogenous cells, we pre-exposed hMSCs with Fsk and transduced with BDNF-adenovirus before transplantation into the brain of memory deficient rats, a degenerating brain disease model induced by ibotenic acid injection. Viability of MSCs and expression of a GABA synthesizing enzyme were increased. The pre-treatment improved learning and memory, as detected by the behavioral tests including Y-maze task and passive avoidance test. These results suggest that TrkB expression of hMSCs elevates the neuronal regeneration and efficiency of BDNF delivery for treating degenerative neurological diseases accompanying memory loss.
authors: Department of Biology, Kyung Hee University, Seoul, Republic of Korea.
authors: Hwon
authors: H
authors: Heo
authors: Minjoo
authors: M
authors: Yoo
authors: Donghoon
authors: D
authors: Han
authors: Yakdol
authors: Y
authors: Cho
authors: Insil
authors: I
authors: Joung
authors: Yunhee Kim
authors: YK
authors: Kwon
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology*; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D008569:Memory Disorders / Q000628:therapy*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000096:biosynthesis*; D020127:Recovery of Function / Q000187:drug effects; D012038:Regeneration / Q000187:drug effects*; D014161:Transduction, Genetic; D015854:Up-Regulation; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D005576:Colforsin; D005680:gamma-Aminobutyric Acid; D020813:Receptor, trkB; D000262:Adenylyl Cyclases