title: Differential regulation of ABCA1 and ABCG1 gene expressions in the remodeling mouse hippocampus after entorhinal cortex lesion and liver-X receptor agonist treatment.
abstract: 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 -A1 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 time-dependent 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.
authors.affiliation: Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada H4A 2B4; Douglas Mental Health University Institute, 6875 LaSalle Blvd, Verdun, Quebec, Canada H4H 1R3.
authors.forename: Stéphanie Bélanger
authors.initials: SB
authors.lastname: Jasmin
authors.affiliation: Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada H4A 2B4; Douglas Mental Health University Institute, 6875 LaSalle Blvd, Verdun, Quebec, Canada H4H 1R3.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Pearson
authors.affiliation: Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada H4A 2B4; Douglas Mental Health University Institute, 6875 LaSalle Blvd, Verdun, Quebec, Canada H4H 1R3.
authors.forename: Daphnée
authors.initials: D
authors.lastname: Lalonde
authors.affiliation: Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada H4A 2B4; Douglas Mental Health University Institute, 6875 LaSalle Blvd, Verdun, Quebec, Canada H4H 1R3.
authors.forename: Dorothée
authors.initials: D
authors.lastname: Domenger
authors.affiliation: Douglas Mental Health University Institute, 6875 LaSalle Blvd, Verdun, Quebec, Canada H4H 1R3.
authors.forename: Louise
authors.initials: L
authors.lastname: Théroux
authors.affiliation: Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada H4A 2B4; Douglas Mental Health University Institute, 6875 LaSalle Blvd, Verdun, Quebec, Canada H4H 1R3. Electronic address: judes.poirier@mcgill.ca.
authors.forename: Judes
authors.initials: J
authors.lastname: Poirier
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics* / Q000378:metabolism; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D018728:Entorhinal Cortex / Q000187:drug effects / Q000293:injuries* / Q000473:pathology; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D007839:Functional Laterality; D058851:GPI-Linked Proteins / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology; D008074:Lipoproteins / Q000235:genetics* / Q000378:metabolism; D000071518:Liver X Receptors; D008297:Male; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology; D057093:Orphan Nuclear Receptors / Q000819:agonists* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D016708:Synaptophysin / Q000378:metabolism; D013997:Time Factors; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
chemical_list: D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D000110:Acetylcholinesterase; D058851:GPI-Linked Proteins; D006845:Hydrocarbons, Fluorinated; D008074:Lipoproteins; D000071518:Liver X Receptors; D018696:Neuroprotective Agents; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger; D013449:Sulfonamides; D016708:Synaptophysin; C577833:Abca1 protein, mouse; C487540:ABCG1 protein, mouse; C569015:Syp protein, mouse; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides; C548245:Ache protein, mouse
keywords: ATP-binding cassette transporter; Apolipoprotein E; Cholesterol; LXR; Reinnervation; TO901317