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

TLR4 Gene Expression and Pro-Inflammatory Cytokines in Alzheimer’s Disease and in Response to Hippocampal Deafferentation in Rodents

“…In this model, it is possible to examine, in a plaque-free environment, the impact on the gene expression of multiple inflammation-related biomarkers of a) the synaptic loss and the microglial activation present in the first 14 days following the lesion and b) the synaptic remodelling and the cholinergic sprouting in the 14-30 days post-lesion window. [38][39][40] Moreover, this model mimics one of the first neuronal losses observed in AD, namely the degeneration of the perforant path, which consists mostly of projections from layer II entorhinal cortex neurons to the dentate gyrus of the hippocampus. [41] Since synapse loss is the major correlate of cognitive impairment, [42] the ECL mouse model is of great use in monitoring the inflammatory responses that might be involved in AD.…”

Differences in ABCA1 R219K Polymorphisms and Serum Indexes in Alzheimer and Parkinson Diseases in Northern China

“…Adenosine triphosphate (ATP)-binding cassette transporter A1 (ABCA1) is an important element in reverse cholesterol transport and removal of cholesterol from tissues [ 3 ]. ABCA1 was found to participate in the early remodeling process of brain injury, especially apolipoprotein E (ApoE) lipidation and glial cholesterol efflux regulation [ 4 , 5 ]. ABCA1 enhances clearance of Aβ, ameliorating brain injury via the ApoE-mediated pathway, which might be related to the risk of AD [ 6 ].…”

Alzheimer's-associated upregulation of mitochondria-associated ER membranes after traumatic brain injury

“…Elevated CEs have been reported previously [13,56,57], alongside elevations in 18:1 CE specifically [13] as well as the expression of ACAT1 [12]. There are also reports of increased expression of cholesterol transporter APOE [58–60], lipid transporter LDLR [58], and lipid efflux pump ABCA1 [59,61,62]. MAM upregulation likely contributes, in part, to these phenotypes.…”