title: Form follows function: astrocyte morphology and immune dysfunction in SIV neuroAIDS.
abstract: Cortical function is disrupted in neuroinflammatory disorders, including HIV-associated neurocognitive disorders (HAND). Astrocyte dysfunction includes retraction of foot processes from the blood-brain barrier and decreased removal of neurotransmitters from synaptic clefts. Mechanisms of astrocyte activation, including innate immune function and the fine neuroanatomy of astrocytes, however, remain to be investigated. We quantified the number of glial fibrillary acidic protein (GFAP)-labeled astrocytes per square millimeter and the proportion of astrocytes immunopositive for Toll-like receptor 2 (TLR2) to examine innate immune activation in astrocytes. We also performed detailed morphometric analyses of gray and white matter astrocytes in the frontal and parietal lobes of rhesus macaques infected with simian immunodeficiency virus (SIV), both with and without encephalitis, an established model of AIDS neuropathogenesis. Protoplasmic astrocytes (gray matter) and fibrous astrocytes (deep white matter) were imaged, and morphometric features were analyzed using Neurolucida. Gray matter and white matter astrocytes showed no change in cell body size in animals infected with SIV regardless of encephalitic status. In SIV-infected macaques, both gray and white matter astrocytes had shorter, less ramified processes, resulting in decreased cell arbor compared with controls. SIV-infected macaques with encephalitis showed decreases in arbor length in white matter astrocytes and reduced complexity in gray matter astrocytes compared to controls. These results provide the first evidence that innate immune activation of astrocytes is linked to altered cortical astrocyte morphology in SIV/HIV infection. Here, we demonstrate that astrocyte remodeling is correlated with infection. Perturbed neuron-glia signaling may be a driving factor in the development of HAND.
authors: Tulane National Primate Research Center, Covington, LA, USA.
authors: Kim M
authors: KM
authors: Lee
authors: Kevin B
authors: KB
authors: Chiu
authors: Nicole A
authors: NA
authors: Renner
authors: Hope A
authors: HA
authors: Sansing
authors: Peter J
authors: PJ
authors: Didier
authors: Andrew G
authors: AG
authors: MacLean
mesh_terms: D015526:AIDS Dementia Complex / Q000276:immunology / Q000473:pathology; D000818:Animals; D001253:Astrocytes / Q000276:immunology* / Q000473:pathology*; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000473:pathology*