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Upregulation of neuronal nicotinic receptor subunits α4, β2, and α7 in transgenic mice overexpressing human acetylcholinesterase

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Abstract

Neuronal nicotinic receptor binding sites as well as mRNA levels encoding for subunits α4, β2, and α7 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]αbungarotoxin binding in the cortex and the caudate putamen of these mice. Quantitative in situ hybridization showed significant upregulation of mRNA corresponding to the nicotinic receptor subunits α4, β2, and α7 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.

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Authors and Affiliations

  1. Karolinska Institutet, NEUROTEC, Division of Molecular Neuropharmacology, Huddinge University Hospital, B84, S141 86, Stockholm, Sweden

    Marie M. Svedberg, Anne-Lie Svensson & Agneta Nordberg

  2. MRC Neurochemical Pathology Unit, Newcastle General Hospital, NE4 6BE, Newcastle upon Tyne, UK

    Mary Johnson, Mandy Lee, Jennifer Court & Elaine Perry

  3. Department of Biological Chemistry, Life Sciences Institute, Hebrew University of Jerusalem, Jerusalem, Israel

    Osnat Cohen & Hermona Soreq

Authors
  1. Marie M. Svedberg
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  2. Anne-Lie Svensson
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  3. Mary Johnson
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  4. Mandy Lee
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  5. Osnat Cohen
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  6. Jennifer Court
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  7. Hermona Soreq
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  8. Elaine Perry
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  9. Agneta Nordberg
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Correspondence to Marie M. Svedberg.

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Svedberg, M.M., Svensson, AL., Johnson, M. et al. Upregulation of neuronal nicotinic receptor subunits α4, β2, and α7 in transgenic mice overexpressing human acetylcholinesterase. J Mol Neurosci 18, 211–222 (2002). https://doi.org/10.1385/JMN:18:3:211

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  • DOI: https://doi.org/10.1385/JMN:18:3:211

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