Donepezil rescues spatial learning and memory deficits following traumatic brain injury independent of its effects on neurogenesis.

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...

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Main Authors: Tzong-Shiue Yu, Ahleum Kim, Steven G Kernie
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4340948?pdf=render
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author Tzong-Shiue Yu
Ahleum Kim
Steven G Kernie
author_facet Tzong-Shiue Yu
Ahleum Kim
Steven G Kernie
author_sort Tzong-Shiue Yu
collection DOAJ
description 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.
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spelling doaj.art-6d0183e9266d49c095f06c627842bc4c2022-12-22T01:52:05ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01102e011879310.1371/journal.pone.0118793Donepezil rescues spatial learning and memory deficits following traumatic brain injury independent of its effects on neurogenesis.Tzong-Shiue YuAhleum KimSteven G KernieTraumatic 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.http://europepmc.org/articles/PMC4340948?pdf=render
spellingShingle Tzong-Shiue Yu
Ahleum Kim
Steven G Kernie
Donepezil rescues spatial learning and memory deficits following traumatic brain injury independent of its effects on neurogenesis.
PLoS ONE
title Donepezil rescues spatial learning and memory deficits following traumatic brain injury independent of its effects on neurogenesis.
title_full Donepezil rescues spatial learning and memory deficits following traumatic brain injury independent of its effects on neurogenesis.
title_fullStr Donepezil rescues spatial learning and memory deficits following traumatic brain injury independent of its effects on neurogenesis.
title_full_unstemmed Donepezil rescues spatial learning and memory deficits following traumatic brain injury independent of its effects on neurogenesis.
title_short Donepezil rescues spatial learning and memory deficits following traumatic brain injury independent of its effects on neurogenesis.
title_sort donepezil rescues spatial learning and memory deficits following traumatic brain injury independent of its effects on neurogenesis
url http://europepmc.org/articles/PMC4340948?pdf=render
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AT ahleumkim donepezilrescuesspatiallearningandmemorydeficitsfollowingtraumaticbraininjuryindependentofitseffectsonneurogenesis
AT stevengkernie donepezilrescuesspatiallearningandmemorydeficitsfollowingtraumaticbraininjuryindependentofitseffectsonneurogenesis