Alteration of hippocampal cell proliferation in mice lacking the beta 2 subunit of the neuronal nicotinic acetylcholine receptor.
Adult hippocampal neurogenesis declines with age in parallel with decreased performance on a variety of hippocampal-dependent tasks. We measured the rate of cellular proliferation in the hippocampus of mice lacking the beta 2-subunit of the nicotinic acetylcholine receptor (beta 2-/- mice) at three ages: young adult (3 months old), fully adult (7-10 months old), and aged (22-24 months old). Consistent with previous studies, we observed an age-related decline in hippocampal proliferation in both groups. However, in fully adult beta 2-/- mice a 43% reduction of granule cell proliferation was detected compared to age-matched controls. This was accompanied by a significant decrease in dentate gyrus area/section and the length of the granule cell layer in beta 2-/- mice. These alterations were not the result of a change in plasma corticosterone levels or expression of the neurotrophic factor BDNF in the dentate gyrus, two known regulators of hippocampal cell proliferation. Similarly, there was no increase in gliosis, abnormal myelination, or apoptotic cell death in the beta 2-/- animals, although there was a significant shift in the location of apoptotic cells in the dentate gyrus indicative of a change in neuronal survival. These results suggest that the beta 2-subunit containing nicotinic acetylcholine receptors play an important role in regulating cell proliferation in the hippocampus and that endogenous acetylcholine may act to oppose the negative effects of normal aging and stress on cellular proliferation.
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06508, USA.
Alexia
A
Harrist
Robert D
RD
Beech
Sarah L
SL
King
Alessio
A
Zanardi
Muriel A
MA
Cleary
Barbara J
BJ
Caldarone
Amelia
A
Eisch
Michele
M
Zoli
Marina R
MR
Picciotto
D000375:Aging / Q000473:pathology / Q000502:physiology; D000818:Animals; D017209:Apoptosis; D002455:Cell Division / Q000502:physiology; D005260:Female; D005911:Gliosis / Q000473:pathology; D006624:Hippocampus / Q000166:cytology* / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology* / Q000502:physiology; D011978:Receptors, Nicotinic / Q000235:genetics*
D011978:Receptors, Nicotinic