Galanin transgenic mice display cognitive and neurochemical deficits characteristic of Alzheimer's disease.
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 beta-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.
Department of Obstetrics and Gynecology, University of Washington, Seattle, WA 98195-7290, USA.
R A
RA
Steiner
J G
JG
Hohmann
A
A
Holmes
C C
CC
Wrenn
G
G
Cadd
A
A
Juréus
D K
DK
Clifton
M
M
Luo
M
M
Gutshall
S Y
SY
Ma
E J
EJ
Mufson
J N
JN
Crawley
D000544:Alzheimer Disease / Q000378:metabolism / Q000523:psychology*; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D003072:Cognition Disorders / Q000209:etiology*; D004195:Disease Models, Animal; D019004:Galanin / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism; D016548:Prosencephalon / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D011950:Receptors, Cholinergic / Q000378:metabolism
D012333:RNA, Messenger; D011950:Receptors, Cholinergic; D019004:Galanin