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Decrease of aquaporin-4 and excitatory amino acid transporter-2 indicate astrocyte dysfunction for pathogenesis of cortical degeneration in HIV-associated neurocognitive disorders.
- Source :
-
Neuropathology : official journal of the Japanese Society of Neuropathology [Neuropathology] 2017 Feb; Vol. 37 (1), pp. 25-34. Date of Electronic Publication: 2016 Aug 10. - Publication Year :
- 2017
-
Abstract
- Human immunodeficiency virus (HIV) encephalitis and degeneration of cerebral cortex are established histopathologies of HIV-associated neurocognitive disorders (HAND). We previously reported decreased excitatory amino acid transporter-2 (EAAT-2) and astrocytic apoptosis in cortical degeneration using SIVmac239 and simian-human immunodeficiency virus (SHIV)-infected macaques and human AIDS autopsy cases. In the present study, we added highly pathogenic SIVsm543-3-infected macaques. These animals showed similar degenerative changes in the frontal cortex. Using 11 SIV-infected macaques, three SIVsm543-3, five SIVmac239 and three SHIV, we compared brain pathology caused by three different viruses and further analyzed the pathogenic process of HAND. We noticed vacuolar changes in perivascular processes of astrocytes by electron microscopy, and examined expression of astrocyte-specific protein aquaporin-4 (AQP4) by immunohistochemistry. APQ4 was diffusely positive in the neuropil and perivascular area in control brains. There was patchy or diffuse decrease of AQP4 staining in the neuropil of SIV-infected macaques, which was associated with EAAT-2 staining by double immunostaining. A quantitative analysis demonstrated significant positive correlation between areas of AQP4 and EAAT-2. Some astrocytes express EAAT-2 but not AQP4, and decrease of EAAT-2 expression tended to be less than the decrease of AQP4. Active-caspase-3 immunostaining demonstrated apoptosis of neurons and astrocytes in the area of AQP4/EAAT-2 reduction. These results suggest that AQP4 is damaged first and decrease of EAAT-2 may follow in pathogenesis of cortical degeneration. This is the first demonstration of decrease of AQP4 and its association with EAAT-2 decrease in AIDS brain, suggesting a role in the pathogenesis of HAND.<br /> (© 2016 Japanese Society of Neuropathology.)
- Subjects :
- AIDS Dementia Complex pathology
Animals
Apoptosis physiology
Astrocytes pathology
Brain pathology
Caspase 3 metabolism
Female
Macaca mulatta
Male
Neurons metabolism
Neurons pathology
Neuropil metabolism
Neuropil pathology
Simian Immunodeficiency Virus
AIDS Dementia Complex metabolism
Aquaporin 4 metabolism
Astrocytes metabolism
Brain metabolism
Excitatory Amino Acid Transporter 2 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1440-1789
- Volume :
- 37
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Neuropathology : official journal of the Japanese Society of Neuropathology
- Publication Type :
- Academic Journal
- Accession number :
- 27506782
- Full Text :
- https://doi.org/10.1111/neup.12321