Upregulation of neuronal nicotinic receptor subunits alpha4, beta2, and alpha7 in transgenic mice overexpressing human acetylcholinesterase

J Mol Neurosci. 2002 Jun;18(3):211-22. doi: 10.1385/JMN:18:3:211.

Abstract

Neuronal nicotinic receptor binding sites as well as mRNA levels encoding for subunits alpha4, beta2, and alpha7 were analysed in 3-mo-old transgenic mice generated with a neuronal overexpression of human acetylcholinesterase and in age-matched controls. The acetylcholinesterase transgenic mice display progressive cognitive impairment in spatial learning and memory. We here report a significantly increased [3H]epibatidine and [125I]alphabungarotoxin binding in the cortex and the caudate putamen of these mice. Quantitativein situ hybridization showed significant upregulation of mRNA corresponding to the nicotinic receptor subunits alpha4, beta2, and alpha7 in various brain regions in the transgenic mice compared to nontransgenic controls. Our results suggest that disruption of balanced cholinergic transmission by constitutive overexpression of acetylcholinesterase is accompanied by variable upregulation of several nicotinic receptor subtypes, in particular these associated with cholinergic terminals participating in compensatory response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / genetics
  • Acetylcholinesterase / metabolism*
  • Animals
  • Autoradiography
  • Brain / anatomy & histology
  • Brain / physiology
  • Bridged Bicyclo Compounds, Heterocyclic / metabolism
  • Bungarotoxins / metabolism
  • Butyrylcholinesterase / metabolism
  • Female
  • Humans
  • In Situ Hybridization
  • Learning / physiology
  • Male
  • Memory / physiology
  • Mice
  • Mice, Transgenic
  • Neurons / cytology
  • Neurons / physiology*
  • Nicotinic Agonists / metabolism
  • Protein Subunits
  • Pyridines / metabolism
  • Receptors, Nicotinic / genetics
  • Receptors, Nicotinic / metabolism*
  • Statistics as Topic
  • Up-Regulation / physiology*
  • alpha7 Nicotinic Acetylcholine Receptor

Substances

  • Bridged Bicyclo Compounds, Heterocyclic
  • Bungarotoxins
  • Chrna7 protein, human
  • Chrna7 protein, mouse
  • Nicotinic Agonists
  • Protein Subunits
  • Pyridines
  • Receptors, Nicotinic
  • alpha7 Nicotinic Acetylcholine Receptor
  • nicotinic acetylcholine receptor alpha4 subunit
  • nicotinic receptor beta2
  • Acetylcholinesterase
  • Butyrylcholinesterase
  • epibatidine