title: Long-term potentiation promotes proliferation/survival and neuronal differentiation of neural stem/progenitor cells.
abstract: Neural stem cell (NSC) replacement therapy is considered a promising cell replacement therapy for various neurodegenerative diseases. However, the low rate of NSC survival and neurogenesis currently limits its clinical potential. Here, we examined if hippocampal long-term potentiation (LTP), one of the most well characterized forms of synaptic plasticity, promotes neurogenesis by facilitating proliferation/survival and neuronal differentiation of NSCs. We found that the induction of hippocampal LTP significantly facilitates proliferation/survival and neuronal differentiation of both endogenous neural progenitor cells (NPCs) and exogenously transplanted NSCs in the hippocampus in rats. These effects were eliminated by preventing LTP induction by pharmacological blockade of the N-methyl-D-aspartate glutamate receptor (NMDAR) via systemic application of the receptor antagonist, 3-[(R)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid (CPP). Moreover, using a NPC-neuron co-culture system, we were able to demonstrate that the LTP-promoted NPC neurogenesis is at least in part mediated by a LTP-increased neuronal release of brain-derived neurotrophic factor (BDNF) and its consequent activation of tropomysosin receptor kinase B (TrkB) receptors on NSCs. Our results indicate that LTP promotes the neurogenesis of both endogenous and exogenously transplanted NSCs in the brain. The study suggests that pre-conditioning of the host brain receiving area with a LTP-inducing deep brain stimulation protocol prior to NSC transplantation may increase the likelihood of success of using NSC transplantation as an effective cell therapy for various neurodegenerative diseases.
authors.affiliation: Brain Research Centre and Department of Medicine, University of British Columbia, Vancouver, Canada.
authors.forename: Taesup
authors.initials: T
authors.lastname: Cho
authors.forename: Jae K
authors.initials: JK
authors.lastname: Ryu
authors.forename: Changiz
authors.initials: C
authors.lastname: Taghibiglou
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ge
authors.forename: Allen W
authors.initials: AW
authors.lastname: Chan
authors.forename: Lidong
authors.initials: L
authors.lastname: Liu
authors.forename: Jie
authors.initials: J
authors.lastname: Lu
authors.forename: James G
authors.initials: JG
authors.lastname: McLarnon
authors.forename: Yu Tian
authors.initials: YT
authors.lastname: Wang
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D018891:Dentate Gyrus / Q000166:cytology; D057809:HEK293 Cells; D006801:Humans; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000637:transplantation; D055495:Neurogenesis / Q000187:drug effects; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D033581:Stem Cell Transplantation
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D016194:Receptors, N-Methyl-D-Aspartate; D020813:Receptor, trkB