Galanin transgenic mice display cognitive and neurochemical deficits characteristic of Alzheimer's disease

Robert A. Steiner, John G. Hohmann, Andrew Holmes, Craige C. Wrenn, Gary Cadd, Anders Juréus, Donald K. Clifton, Mulon Luo, Mitchell Gutshall, Shuang Y. Ma, Elliott J. Mufson, Jacqueline Crawley

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Abstract

Galanin is a neuropeptide with multiple inhibitory actions on neurotransmission and memory. In Alzheimer's disease (AD), increased galanin-containing fibers hyperinnervate cholinergic neurons within the basal forebrain in association with a decline in cognition. We generated transgenic mice (GAL-tg) that overexpress galanin under the control of the dopamine β-hydroxylase promoter to study the neurochemical and behavioral sequelae of a mouse model of galanin overexpression in AD. Overexpression of galanin was associated with a reduction in the number of identifiable neurons producing acetylcholine in the horizontal limb of the diagonal band. Behavioral phenotyping indicated that GAL-tgs displayed normal general health and sensory and motor abilities; however, GAL-tg mice showed selective performance deficits on the Morris spatial navigational task and the social transmission of food preference olfactory memory test. These results suggest that elevated expression of galanin contributes to the neurochemical and cognitive impairments characteristic of AD.

Original languageEnglish (US)
Pages (from-to)4184-4189
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number7
DOIs
StatePublished - Mar 27 2001
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • General

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    Steiner, R. A., Hohmann, J. G., Holmes, A., Wrenn, C. C., Cadd, G., Juréus, A., Clifton, D. K., Luo, M., Gutshall, M., Ma, S. Y., Mufson, E. J., & Crawley, J. (2001). Galanin transgenic mice display cognitive and neurochemical deficits characteristic of Alzheimer's disease. Proceedings of the National Academy of Sciences of the United States of America, 98(7), 4184-4189. https://doi.org/10.1073/pnas.061445598