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

doi:10.1073/pnas.061445598

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

Departments of ^*Obstetrics and Gynecology, ^†Physiology and Biophysics, and ^‡Zoology, ^§Graduate Program in Neurobiology and Behavior, University of Washington, Seattle, WA 98195-7290; ^¶Section on Behavioral Neuropharmacology, National Institute of Mental Health, Building 10, Room 4D11, Bethesda, MD 20892-1375; and ^‖Neurological Sciences, Rush Presbyterian–St. Luke's Medical Center, 2242 West Harrison Street, Suite 200, Chicago, IL 60612

Edited by Richard F. Thompson, University of Southern California, Los Angeles, CA, and approved December 21, 2000 (received for review September 15, 2000)

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.

Footnotes

↵ ** To whom reprint requests should be addressed. E-mail: jncrawle{at}codon.nih.gov.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations:

AD,

Alzheimer's disease;

GAL-tg,

galanin transgenic;

WT,

wild type;

hDBH,

human dopamine β-hydroxylase;

ChAT,

choline acetyltransferase;

MS,

medial septum;

VDB,

vertical limb diagonal band;

HDB,

horizontal limb diagonal band