Neural stem cells improve memory in an inducible mouse model of neuronal loss.
Neuronal loss is a major pathological outcome of many common neurological disorders, including ischemia, traumatic brain injury, and Alzheimer disease. Stem cell-based approaches have received considerable attention as a potential means of treatment, although it remains to be determined whether stem cells can ameliorate memory dysfunction, a devastating component of these disorders. We generated a transgenic mouse model in which the tetracycline-off system is used to regulate expression of diphtheria toxin A chain. After induction, we find progressive neuronal loss primarily within the hippocampus, leading to specific impairments in memory. We find that neural stem cells transplanted into the brain after neuronal ablation survive, migrate, differentiate and, most significantly, improve memory. These results show that stem cells may have therapeutic value in diseases and conditions that result in memory loss.
Yamasaki
Tritia R
TR
Department of Neurobiology and Behavior, University of California, Irvine, Irvine, California 92697, USA.
Blurton-Jones
Mathew
M
Morrissette
Debbi A
DA
Kitazawa
Masashi
M
Oddo
Salvatore
S
LaFerla
Frank M
FM
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D001927:Brain Diseases / Q000150:complications / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D001973:Bromodeoxyuridine / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics; D002452:Cell Count / Q000379:methods; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D004167:Diphtheria Toxin / Q000096:biosynthesis / Q000633:toxicity; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins / Q000096:biosynthesis; D020287:In Situ Nick-End Labeling / Q000379:methods; D008569:Memory Disorders / Q000209:etiology / Q000601:surgery*; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000473:pathology* / Q000502:physiology*; D010446:Peptide Fragments / Q000096:biosynthesis / Q000633:toxicity; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D033581:Stem Cell Transplantation / Q000379:methods*; D013752:Tetracycline / Q000378:metabolism
D004167:Diphtheria Toxin; D010446:Peptide Fragments; C029795:diphtheria toxin fragment A; D049452:Green Fluorescent Proteins; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D010751:Phosphopyruvate Hydratase; D013752:Tetracycline; D001973:Bromodeoxyuridine