Remodeling Of Astrocyte Morphology During Reactive Astrogliosis Is Dependent On Pathology
Description
Astrocytes display a complex, stellate morphology in the brain, commensurate with their role in regulating nearly every functional aspect of the central nervous system. Innate activation of astrocytes is a classic hallmark of neurologic injury and disorder, characterized by proliferation, process hypertrophy, and transition toward polygonal morphology. However, the extent and consistency of these morphological changes, especially in the context of distinct pathologies, remain largely unknown. Here, changes in the fine neuroanatomy of astrocytes in rhesus macaque monkeys were characterized under a variety of conditions with relevance to translational research, including autistic-like behavior, bacterial and viral infections. Brain slices from paraffin embedded tissue archives were stained for glial fibrillary acidic protein, a reactive astrocyte marker, and imaged for both grey and white matter astrocytes. These cells were 3D-reconstructed in Neurolucida software and morphometric data including soma size, process length, volume and branching were analyzed and aggregated by animal and condition. It was found that process complexity in white matter astrocytes atrophied during lentiviral infection and depressive behavior, with decreased arbor length and tip quantity observed in SIV-infected and self-injuring animals. However, the opposite was seen during a bacterial infection, with increased arbor complexity and process length seen in Brucella-infected animals. Additionally, astrocytes from animals receiving oral naltrexone treatment for self-injurious behavior displayed a reversion from atrophied cell phenotypes back to original, control morphology. Thus, astrocyte activation and subsequent remodeling is not consistent, but rather context-dependent on the specific pathology and cellular subtype, and may be a driving factor in neurocognitive disorder.