Journal
BRAIN RESEARCH
Volume 1562, Issue -, Pages 39-51Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.brainres.2014.03.016
Keywords
ATP-binding cassette transporter; Apolipoprotein E; Cholesterol; Reinnervation; LXR; TO901317
Categories
Funding
- Canadian Institutes of Health Research
- Natural Sciences and Engineering Research Council of Canada
- Alzheimer Society of Canada
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Entorhinal cortex lesioning (ECL) causes an extensive deafferentation of the hippocampus that is classically followed by a compensatory reinnervation, where apolipoprotein E, the main extracellular lipid-carrier in the CNS, has been shown to play a crucial role by shuttling cholesterol to reconstructing neurons terminals. Hence, we investigated whether the ATP-binding cassette (ABC) transporters -Al and -G1, known to regulate cellular cholesterol efflux and lipidation of the apolipoprotein E-containing lipoprotein complex are actively involved in this context of brain's plastic response to neurodegeneration and deafferentation. We assessed ABCA1 and ABCG1 mRNA and protein levels throughout the degenerative phase and the reinnervation process and evaluated the associated cholinergic sprouting following ECL in the adult mouse brain. We subsequently tested the effect of the pharmacological activation of the nuclear receptor LXR, prior to versus after ECL, on hippocampal ABCA1 and G1 expression and on reinnervation. ECL induced a timedependent up-regulation of ABCA1, but not G1, that coincided with a significant increase in acetylcholine esterase (AChE) activity in the ipsilateral hippocampus. Pre-ECL, but not post-ECL i.p. treatment with the LXR agonist TO901317 also led to a significant increase solely in hippocampal ABCA1 expression, paralleled by increases in both AchE and synaptophysin protein levels in the deafferented hippocampus. Thus, ABCA1 and -G1 are differentially regulated in the lesioned brain and upon treatment with an LXR agonist. Further, TO901317-induced up-regulation of ABCA1 appears to be more beneficial in a prevention (pre-lesion) than rescue (post-lesion) treatment; both findings support a central role for ABC transporters in brain plasticity.(c) 2014 Elsevier B.V. All rights reserved.
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