Effect of voluntary running on adult hippocampal neurogenesis in cholinergic lesioned mice.
BACKGROUND
Cholinergic neuronal dysfunction of the basal forebrain is observed in patients with Alzheimer's disease and dementia, and has been linked to decreased neurogenesis in the hippocampus, a region involved in learning and memory. Running is a robust inducer of adult hippocampal neurogenesis. This study aims to address the effect of running on hippocampal neurogenesis in lesioned mice, where septohippocampal cholinergic neurones have been selectively eliminated in the medial septum and diagonal band of Broca of the basal forebrain by infusion of mu-p75-saporin immunotoxin.


RESULTS
Running increased the number of newborn cells in the dentate gyrus of the hippocampus in cholinergic denervated mice compared to non-lesioned mice 24 hours after injection of bromodeoxyuridine (BrdU). Although similar levels of surviving cells were present in cholinergic depleted animals and their respective controls four weeks after injection of BrdU, the majority of progenitors that proliferate in response to the initial period of running were not able to survive beyond one month without cholinergic input. Despite this, the running-induced increase in the number of surviving neurones was not affected by cholinergic depletion.


CONCLUSIONS
The lesion paradigm used here models aspects of the cholinergic deficits associated with Alzheimer's Disease and aging. We showed that running still increased the number of newborn cells in the adult hippocampal dentate gyrus in this model of neurodegenerative disease.
Ho
New Fei
NF
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Centre for Life Sciences (CeLS), Level 4, 28 Medical Drive, 117456, Singapore. g0300957@nus.edu.sg
Han
Siew Ping
SP
Dawe
Gavin S
GS
D000109:Acetylcholine / Q000378:metabolism*; D053687:Adult Stem Cells / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal; D001522:Behavior, Animal; D001930:Brain Injuries / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000534:rehabilitation; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D049109:Cell Proliferation; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000378:metabolism* / Q000503:physiopathology*; D051379:Mice; D055495:Neurogenesis / Q000502:physiology*; D054789:Ribosome Inactivating Proteins, Type 1; D012420:Running; D000076985:Saporins
C085696:192 IgG-saporin; D000911:Antibodies, Monoclonal; D054789:Ribosome Inactivating Proteins, Type 1; D002795:Choline O-Acetyltransferase; D000076985:Saporins; D001973:Bromodeoxyuridine; D000109:Acetylcholine