PMID- 19183259 OWN - NLM STAT- MEDLINE DCOM- 20090402 LR - 20131121 IS - 1471-4159 (Electronic) IS - 0022-3042 (Linking) VI - 108 IP - 6 DP - 2009 Mar TI - Lithium enhances the neuronal differentiation of neural progenitor cells in vitro and after transplantation into the avulsed ventral horn of adult rats through the secretion of brain-derived neurotrophic factor. PG - 1385-98 LID - 10.1111/j.1471-4159.2009.05902.x [doi] AB - This study was undertaken to elucidate the molecular mechanisms by which lithium regulates the development of spinal cord-derived neural progenitor cells (NPCs) in vitro and after transplanted in vivo. Our results show that lithium at the therapeutic concentration significantly increases the proliferation and neuronal differentiation of NPCs in vitro. Specific ELISAs, western blotting, and quantitative real-time RT-PCR assays demonstrate that lithium treatment significantly elevates the expression and production of brain-derived neurotrophic factor (BDNF) by NPCs in culture. Application of a BDNF neutralizing antibody in culture leads to a marked reduction in the neurogenesis of lithium-treated NPCs to the control level. However, it shows no effects on the proliferation of lithium-treated NPCs. These findings suggest that the BDNF pathway is possibly involved in the supportive role of lithium in inducing NPC neurogenesis but not proliferation. This study also provides evidence that lithium is able to elevate the neuronal generation and BDNF production of NPCs after transplantation into the adult rat ventral horn with motoneuron degeneration because of spinal root avulsion, which highlights the therapeutic potential of lithium in cell replacement strategies for spinal cord injury because of its ability to promote neuronal differentiation and BDNF production of grafted NPCs in the injured spinal cord. FAU - Su, Huanxing AU - Su H AD - Department of Anatomy, Development and Growth, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China. FAU - Zhang, Wenming AU - Zhang W FAU - Guo, Jiasong AU - Guo J FAU - Guo, Anchen AU - Guo A FAU - Yuan, Qiuju AU - Yuan Q FAU - Wu, Wutian AU - Wu W LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090122 PL - England TA - J Neurochem JT - Journal of neurochemistry JID - 2985190R RN - 0 (Antibodies) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Nerve Tissue Proteins) RN - 147336-22-9 (Green Fluorescent Proteins) RN - G34N38R2N1 (Bromodeoxyuridine) RN - G4962QA067 (Lithium Chloride) SB - IM MH - Analysis of Variance MH - Animals MH - Animals, Genetically Modified MH - Animals, Newborn MH - Anterior Horn Cells/cytology MH - Antibodies/pharmacology MH - Brain-Derived Neurotrophic Factor/immunology/*metabolism MH - Bromodeoxyuridine/metabolism MH - Cell Differentiation/*drug effects MH - Cell Transplantation/methods MH - Cells, Cultured MH - Embryo, Mammalian MH - Enzyme-Linked Immunosorbent Assay/methods MH - Female MH - Green Fluorescent Proteins/genetics MH - Lithium Chloride/*pharmacology MH - Nerve Tissue Proteins/metabolism MH - Neurogenesis/*drug effects MH - Neurons/*drug effects MH - Rats MH - Rats, Sprague-Dawley MH - Spinal Nerve Roots/cytology/metabolism/surgery MH - Stem Cells/*drug effects EDAT- 2009/02/03 09:00 MHDA- 2009/04/03 09:00 CRDT- 2009/02/03 09:00 PHST- 2009/02/03 09:00 [entrez] PHST- 2009/02/03 09:00 [pubmed] PHST- 2009/04/03 09:00 [medline] AID - JNC5902 [pii] AID - 10.1111/j.1471-4159.2009.05902.x [doi] PST - ppublish SO - J Neurochem. 2009 Mar;108(6):1385-98. doi: 10.1111/j.1471-4159.2009.05902.x. Epub 2009 Jan 22.