Cognition, learning behaviour and hippocampal synaptic plasticity are not disrupted in mice over-expressing the cholesterol transporter ABCG1.
BACKGROUND
Cognitive deficits are a hallmark feature of both Down Syndrome (DS) and Alzheimer's Disease (AD). Extra copies of the genes on chromosome 21 may also play an important role in the accelerated onset of AD in DS individuals. Growing evidence suggests an important function for cholesterol in the pathogenesis of AD, particularly in APP metabolism and production of A beta peptides. The ATP-Binding Cassette-G1 (ABCG1) transporter is located on chromosome 21, and participates in the maintenance of tissue cholesterol homeostasis.


RESULTS
To assess the role of ABCG1 in DS-related cognition, we evaluated the cognitive performance of mice selectively over-expressing the ABCG1 gene from its endogenous regulatory signals. Both wild-type and ABCG1 transgenic mice performed equivalently on several behavioral tests, including measures of anxiety, as well as on reference and working memory tasks. No deficits in hippocampal CA1 synaptic plasticity as determined with electrophysiological studies were apparent in mice over-expressing ABCG1.


CONCLUSIONS
These findings indicate that although ABCG1 may play a role in maintaining cellular or tissue cholesterol homeostasis, it is unlikely that excess ABCG1 expression contributes to the cognitive deficits in DS individuals.
Parkinson
Pamela F
PF
The Department of Pathology and Laboratory Medicine, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada. parkinsonpam@gmail.com
Kannangara
Timal S
TS
Eadie
Brennan D
BD
Burgess
Braydon L
BL
Wellington
Cheryl L
CL
Christie
Brian R
BR
D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D001007:Anxiety; D001522:Behavior, Animal / Q000502:physiology*; D001692:Biological Transport; D001921:Brain / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D003071:Cognition; D005260:Female; D006624:Hippocampus / Q000502:physiology*; D007858:Learning; D008074:Lipoproteins / Q000378:metabolism*; D008568:Memory; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity; D009473:Neuronal Plasticity / Q000502:physiology*; D009928:Organ Specificity; D013569:Synapses / Q000378:metabolism*
C487540:ABCG1 protein, mouse; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D008074:Lipoproteins; D002784:Cholesterol