title: Differential fate and functional outcome of lithium chloride primed adult neural progenitor cell transplants in a rat model of Huntington disease.
abstract: BACKGROUND
  The ability to predetermine the fate of transplanted neural progenitor cells (NPCs) and specifically to direct their maturation has the potential to enhance the efficiency of cell-transplantation therapy for neurodegenerative disease. We previously demonstrated that transient exposure of subventricular zone (SVZ)-derived adult NPCs to lithium chloride during in vitro proliferation alters differential fate in vitro and increases the proportion of cells expressing neuronal markers while reducing glial progeny. To extend these findings, we examined whether in vitro priming of adult SVZ-derived NPCs with lithium chloride before transplantation into the quinolinic acid (QA) lesion rat model of Huntington disease altered in vivo neuronal differentiation and sensorimotor function compared with nonprimed NPC transplants.
  
  
  METHODS
  NPCs were isolated from the SVZ of the adult rat brain and cultured for 2 weeks. Four days before transplantation into the QA-lesioned rat striatum, the cells were labeled with BrdU and primed with lithium chloride. The rats underwent regular evaluation of forelimb use and sensorimotor neglect to establish functional effects of NPC transplantation. Twelve weeks after transplantation, the brains were analyzed with immunohistochemistry to compare the differential fate of primed and nonprimed NPCs.
  
  
  RESULTS
  We observed that in vitro priming of adult NPCs with lithium chloride reduced gliogenesis and enhanced the occurrence of DARPP-32-positive neurons when compared with nonprimed cells 12 weeks after transplantation into the QA-lesioned striatum. Lithium chloride priming also augmented the formation of efferent projections from newly formed neurons in the damaged host striatum to the globus pallidus. This was associated with acceleration of sensorimotor function recovery in rats receiving transplants of lithium chloride-primed adult NPCs compared with nonprimed transplants.
  
  
  CONCLUSIONS
  These initial findings indicate that in vitro priming of adult NPCs with lithium chloride may augment transplant efficiency and accelerate sensorimotor function outcome in vivo.
authors.affiliation: Department of Pharmacology and Clinical Pharmacology, Centre for Brain Research, Faculty of Medical Health Sciences, The University of Auckland, Private Bag 92019, Auckland Mail Centre, Auckland 1142, New Zealand. vazey@musc.edu
authors.forename: Elena M
authors.initials: EM
authors.lastname: Vazey
authors.forename: Bronwen
authors.initials: B
authors.lastname: Connor
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D053687:Adult Stem Cells / Q000187:drug effects / Q000637:transplantation*; D000818:Animals; D001921:Brain / Q000166:cytology / Q000601:surgery; D002465:Cell Movement; D002470:Cell Survival; D064987:Cell- and Tissue-Based Therapy / Q000379:methods; D002478:Cells, Cultured; D004195:Disease Models, Animal; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000378:metabolism; D006816:Huntington Disease / Q000628:therapy*; D018021:Lithium Chloride / Q000494:pharmacology*; D008297:Male; D058953:Neural Stem Cells / Q000187:drug effects / Q000637:transplantation*; D055495:Neurogenesis / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D055748:SOXB1 Transcription Factors / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D055748:SOXB1 Transcription Factors; C527784:Sox2 protein, rat; D018021:Lithium Chloride