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Early and progressive accumulation of reactive microglia in the Huntington disease brain
1Department of Neurology, Massachusetts General Hospital, Boston 02129, USA.
Abstract:
Microglia may contribute to cell death in neurodegenerative diseases. We studied the activation of microglia in affected regions of Huntington disease (HD) brain by localizing thymosin beta-4 (Tbeta4), which is increased in reactive microglia. Activated microglia appeared in the neostriatum, cortex, and globus pallidus and the adjoining white matter of the HD brain, but not in control brain. In the striatum and cortex, reactive microglia occurred in all grades of pathology, accumulated with increasing grade, and grew in density in relation to degree of neuronal loss. The predominant morphology of activated microglia differed in the striatum and cortex. Processes of reactive microglia were conspicuous in low-grade HD, suggesting an early microglia response to changes in neuropil and axons and in the grade 2 and grade 3 cortex, were aligned with the apical dendrites of pyramidal neurons. Some reactive microglia contacted pyramidal neurons with huntingtin-positive nuclear inclusions. The early and proximate association of activated microglia with degenerating neurons in the HD brain implicates a role for activated microglia in HD pathogenesis.
Insights
Activated microglia, identified by thymosin beta-4, are present in Huntington disease (HD) brain regions. Their density correlates with disease severity and neuronal loss, suggesting a role in HD pathogenesis.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Microglia, the immune cells of the brain, are implicated in neurodegenerative diseases.
- Huntington disease (HD) is a progressive neurodegenerative disorder.
- Thymosin beta-4 (Tbeta4) is a protein found to be increased in reactive microglia.
Purpose of the Study:
- To investigate the activation and distribution of microglia in the Huntington disease brain.
- To examine the relationship between microglial activation and disease pathology in HD.
Main Methods:
- Localization of thymosin beta-4 (Tbeta4) in affected brain regions of HD patients.
- Microscopic examination of microglial morphology and density in relation to disease grade and neuronal loss.
Main Results:
- Activated microglia, marked by Tbeta4, were found in the neostriatum, cortex, and globus pallidus of HD brains, but not in control brains.
- Microglial density increased with higher grades of HD pathology and correlated with neuronal loss in the striatum and cortex.
- Reactive microglia showed distinct morphologies and early associations with degenerating neurons, including those with huntingtin inclusions.
Conclusions:
- Activated microglia are a prominent feature in the Huntington disease brain.
- The presence and density of activated microglia suggest an early and significant role in HD pathogenesis.
- Microglial activation may contribute to neuronal dysfunction and cell death in Huntington disease.