title: Donepezil rescues spatial learning and memory deficits following traumatic brain injury independent of its effects on neurogenesis.
abstract: Traumatic brain injury (TBI) is ubiquitous and effective treatments for it remain supportive largely due to uncertainty over how endogenous repair occurs. Recently, we demonstrated that hippocampal injury-induced neurogenesis is one mechanism underlying endogenous repair following TBI. Donepezil is associated with increased hippocampal neurogenesis and has long been known to improve certain aspects of cognition following many types of brain injury through unknown mechanisms. By coupling donepezil therapy with temporally regulated ablation of injury-induced neurogenesis using nestin-HSV transgenic mice, we investigated whether the pro-cognitive effects of donepezil following injury might occur through increasing neurogenesis. We demonstrate that donepezil itself enhances neurogenesis and improves cognitive function following TBI, even when injury-induced neurogenesis was inhibited. This suggests that the therapeutic effects of donepezil in TBI occur separately from its effects on neurogenesis.
authors.affiliation: Departments of Pediatrics and Pathology & Cell Biology, Columbia University College of Physicians and Surgeons, 3959 Broadway, CHN 10-24, New York, NY 10032, United States of America.
authors.forename: Tzong-Shiue
authors.initials: TS
authors.lastname: Yu
authors.affiliation: Departments of Pediatrics and Pathology & Cell Biology, Columbia University College of Physicians and Surgeons, 3959 Broadway, CHN 10-24, New York, NY 10032, United States of America.
authors.forename: Ahleum
authors.initials: A
authors.lastname: Kim
authors.affiliation: Departments of Pediatrics and Pathology & Cell Biology, Columbia University College of Physicians and Surgeons, 3959 Broadway, CHN 10-24, New York, NY 10032, United States of America.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Kernie
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D018891:Dentate Gyrus / Q000187:drug effects; D004195:Disease Models, Animal; D000077265:Donepezil; D005260:Female; D015774:Ganciclovir / Q000031:analogs & derivatives / Q000494:pharmacology; D007189:Indans / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000188:drug therapy*; D051379:Mice; D008822:Mice, Transgenic; D055495:Neurogenesis / Q000187:drug effects*; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D065853:Spatial Learning / Q000187:drug effects*; D000077562:Valganciclovir
chemical_list: D007189:Indans; D010880:Piperidines; D000077265:Donepezil; D000077562:Valganciclovir; D015774:Ganciclovir