Proton magnetic resonance spectroscopy reveals neuroprotection by oral minocycline in a nonhuman primate model of accelerated NeuroAIDS

Autor: Elkan F. Halpern, R. Gilberto Gonzalez, Julian He, Robert Fell, Eva-Maria Ratai, Kenneth C. Williams, Lakshmanan Annamalai, Patrick Autissier, Margaret R. Lentz, Reza Hakimelahi, Jennifer H. Campbell, Chan-Gyu Joo, Susan V. Westmoreland, Tricia H. Burdo, Jeffrey P. Bombardier, Eliezer Masliah
Rok vydání: 2010
Předmět:
Male
Pathology
Pathology/Histopathology
Magnetic Resonance Spectroscopy
Cost effectiveness
Simian Acquired Immunodeficiency Syndrome
lcsh:Medicine
Administration
Oral
Minocycline
Pharmacology
CD8-Positive T-Lymphocytes
Cohort Studies
0302 clinical medicine
lcsh:Science
Neurons
0303 health sciences
Multidisciplinary
biology
Microglia
Glial fibrillary acidic protein
Chemistry
Radiology and Medical Imaging/Magnetic Resonance Imaging
Viral Load
Infectious Diseases/HIV Infection and AIDS
3. Good health
Astrogliosis
DNA-Binding Proteins
medicine.anatomical_structure
Neuroprotective Agents
Virology/Immunodeficiency Viruses
Virology/Animal Models of Infection
Protons
Cell activation
medicine.drug
Research Article
medicine.medical_specialty
Pathology/Immunology
Neuroprotection
Lymphocyte Depletion
03 medical and health sciences
medicine
Animals
Humans
AIDS-Associated Nephropathy
030304 developmental biology
Neurological Disorders/Infectious Diseases of the Nervous System
Infectious Diseases/Infectious Diseases of the Nervous System
lcsh:R
medicine.disease
Macaca mulatta
Disease Models
Animal
nervous system
Synaptophysin
biology.protein
lcsh:Q
030217 neurology & neurosurgery
Biomarkers
Zdroj: PLoS ONE
PLoS ONE, Vol 5, Iss 5, p e10523 (2010)
ISSN: 1932-6203
Popis: Background: Despite the advent of highly active anti-retroviral therapy (HAART), HIV-associated neurocognitive disorders continue to be a significant problem. In efforts to understand and alleviate neurocognitive deficits associated with HIV, we used an accelerated simian immunodeficiency virus (SIV) macaque model of NeuroAIDS to test whether minocycline is neuroprotective against lentiviral-induced neuronal injury. Methodology/Principal Findings: Eleven rhesus macaques were infected with SIV, depleted of CD8+ lymphocytes, and studied until eight weeks post inoculation (wpi). Seven animals received daily minocycline orally beginning at 4 wpi. Neuronal integrity was monitored in vivo by proton magnetic resonance spectroscopy and post-mortem by immunohistochemistry for synaptophysin (SYN), microtubule-associated protein 2 (MAP2), and neuronal counts. Astrogliosis and microglial activation were quantified by measuring glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule 1 (IBA-1), respectively. SIV infection followed by CD8+ cell depletion induced a progressive decline in neuronal integrity evidenced by declining N-acetylaspartate/creatine (NAA/Cr), which was arrested with minocycline treatment. The recovery of this ratio was due to increases in NAA, indicating neuronal recovery, and decreases in Cr, likely reflecting downregulation of glial cell activation. SYN, MAP2, and neuronal counts were found to be higher in minocyclinetreated animals compared to untreated animals while GFAP and IBA-1 expression were decreased compared to controls. CSF and plasma viral loads were lower in MN-treated animals. Conclusions/Significance: In conclusion, oral minocycline alleviates neuronal damage induced by the AIDS virus.
Databáze: OpenAIRE
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