ABSTRACT
Astroglia play an important role, providing de novo synthesized cholesterol to neurons in the form of ApoE-lipidated particles; disruption of this process can increase the risk of Alzheimer's disease. We recently reported that glia-specific suppression of the lipolysis-stimulated lipoprotein receptor (LSR) gene leads to Alzheimer's disease-like memory deficits. Since LSR is an Apo-E lipoprotein receptor, our objective of this study was to determine the effect of LSR expression modulation on cholesterol and ApoE output in mouse astrocytes expressing human ApoE3. qPCR analysis showed that siRNA-mediated lsr knockdown significantly increased expression of the genes involved in cholesterol synthesis, secretion, and metabolism. Analysis of media and lipoprotein fractions showed increased cholesterol and lipidated ApoE output in HDL-like particles. Further, lsr expression could be upregulated when astrocytes were incubated 5 days in media containing high levels (two-fold) of lipoprotein, or after 8 h treatment with 1 µM LXR agonist T0901317 in lipoprotein-deficient media. In both conditions of increased lsr expression, the ApoE output was repressed or unchanged despite increased abca1 mRNA levels and cholesterol production. We conclude that LSR acts as a sensor of lipoprotein content in the medium and repressor of ApoE release, while ABCA1 drives cholesterol efflux, thereby potentially affecting cholesterol load, ApoE lipidation, and limiting cholesterol trafficking towards the neuron.
Subject(s)
Alzheimer Disease , Receptors, Lipoprotein , Alzheimer Disease/metabolism , Animals , Apolipoproteins E/metabolism , Astrocytes/metabolism , Cholesterol/metabolism , Humans , Lipolysis , Mice , Receptors, Lipoprotein/genetics , Receptors, Lipoprotein/metabolismABSTRACT
Background: Carotid Web and focal carotid diaphragm are atypical fibromuscular dysplasia. The bilateral stroke due to this dysplasia is extremely rare. We will report a series of three young patients, admitted for a bilateral ischemic stroke caused by carotid bulb web and internal carotid diaphragm. Also, we will discuss their manifestations and treatment modalities. Case presentations: In our study, we will report a series of three North African patients, two females an one male, at the mean age of 37, admitted for an ischemic stroke caused by bilateral carotid bulb web and bilateral internal carotid diaphragm.All of our patients were young and didn't have a history of drug use. Conclusions: In our series, only end-vascular treatment was performed which was necessary to prevent any recurrence. Antiplatelet therapy was used in all cases to prevent any stroke during the follow-up.
ABSTRACT
Cavernous hemangiomas are rare account representing 5%-13% of the intracranial vascular malformations and occur in approximately 0.5%-1% of the population. We report the case of 34-years-old woman, having a medical history of seizure, admitted for headache with binocular diplopia. The radiology investigation and operatory piece has shown an association of cavernous sinus hemangioma and frontal focal cortical dysplasia. This study highlights clinical, radiological and therapeutic features of this entity.
ABSTRACT
Considering SARS-CoV-2 as a major differential diagnosis of pneumocystis in HIV-positive patients even if the lesions are typical.
