Novel method to quantify phenotypic markers of HIV-associated neurocognitive disorder in a murine SCID model

Autor: Christina Gavegnano, Selwyn J. Hurwitz, James J. Kohler, Raj Koneru, William R. Tyor, Raymond F. Schinazi, Woldeab B. Haile
Rok vydání: 2020
Předmět:
Male
0301 basic medicine
Neurology
HIV Core Protein p24
Gene Expression
HIV Infections
Mice
SCID
HIV-associated neurocognitive disorder
Mice
0302 clinical medicine
Macrophage
Gliosis
Neurons
medicine.diagnostic_test
Microglia
Brain
virus diseases
Astrogliosis
Phenotype
medicine.anatomical_structure
Immunohistochemistry
medicine.symptom
Microtubule-Associated Proteins
medicine.medical_specialty
Inflammation
Article
Flow cytometry
03 medical and health sciences
Cellular and Molecular Neuroscience
Virology
Glial Fibrillary Acidic Protein
medicine
Animals
Humans
Cognitive Dysfunction
business.industry
Macrophages
medicine.disease
Disease Models
Animal
030104 developmental biology
Astrocytes
Immunology
HIV-1
Leukocyte Common Antigens
Neurology (clinical)
business
Biomarkers
030217 neurology & neurosurgery
Zdroj: J Neurovirol
ISSN: 1538-2443
1355-0284
Popis: Despite combined antiretroviral therapy (cART), HIV infection in the CNS persists with reported increases in activation of macrophages (MΦ), microglia, and surrounding astrocytes/neurons, conferring HIV-induced inflammation. Chronic inflammation results in HIV-associated neurocognitive disorders (HAND) with reported occurrence of up to half of individuals with HIV infection. The existing HAND mouse model used by laboratories including ours, and the effect of novel agents on its pathology present with labor-intensive and time-consuming limitations since brain sections and immunohistochemistry assays have to be performed and analyzed. A novel flow cytometry-based system to objectively quantify phenotypic effects of HIV using a SCID mouse HAND model was developed which demonstrated that the HIV-infected mice had significant increases in astrogliosis, loss of neuronal dendritic marker, activation of murine microglia, and human macrophage explants compared to uninfected control mice. HIV p24 could also be quantified in the brains of the infected mice. Correlation of these impairments with HIV-induced brain inflammation and previous behavioral abnormalities studies in mice suggests that this model can be used as a fast and relevant throughput methodology to quantify preclinical testing of novel treatments for HAND.
Databáze: OpenAIRE
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