Alteration of hippocampal cell proliferation in mice lacking the β2 subunit of the neuronal nicotinic acetylcholine receptor

Alexia Harrist, Robert D. Beech, Sarah L. King, Alessio Zanardi, Muriel A. Cleary, Barbara J. Caldarone, Amelia Eisch, Michele Zoli, Marina R. Picciotto

Research output: Contribution to journalArticlepeer-review

68 Scopus citations

Abstract

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 β-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.

Original languageEnglish (US)
Pages (from-to)200-206
Number of pages7
JournalSynapse
Volume54
Issue number4
DOIs
StatePublished - Dec 15 2004

Keywords

  • Adult neurogenesis
  • Aging
  • Dementia
  • Nicotine
  • nAChR

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Alteration of hippocampal cell proliferation in mice lacking the β2 subunit of the neuronal nicotinic acetylcholine receptor'. Together they form a unique fingerprint.

Cite this