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Alteration of hippocampal cell proliferation in mice lacking the β2 subunit of the neuronal nicotinic acetylcholine receptor
Author(s) -
Harrist Alexia,
Beech Robert D.,
King Sarah L.,
Zanardi Alessio,
Cleary Muriel A.,
Caldarone Barbara J.,
Eisch Amelia,
Zoli Michele,
Picciotto Marina R.
Publication year - 2004
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20081
Subject(s) - dentate gyrus , hippocampal formation , neurogenesis , granule cell , nicotinic acetylcholine receptor , endocrinology , medicine , neuroscience , hippocampus , biology , neurotrophic factors , acetylcholine , acetylcholine receptor , 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 β2‐subunit of the nicotinic acetylcholine receptor (β2−/− 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 β2−/− 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 β2−/− 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 β2−/− 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 β2‐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. Synapse 54:200–206, 2004. © 2004 Wiley‐Liss, Inc.