Microglial proliferation and astrocytic protein alterations in the human Huntington's disease cortex

• DOI: 10.1016/j.nbd.2024.106554
• Publication Date: 2024-06-05T11:15:07Z
• Authors: Adelie Y.S. Tan; Lynette J. Tippett; Clinton P. Turner; Molly E.V. Swanson; Thomas I.H. Park; Maurice A. Curtis; Richard L.M. Faull; Mike Dragunow; Malvindar K. Sing...
• Keywords: Gliosis

Huntington's disease (HD) is a neurodegenerative disorder that severely affects the basal ganglia and regions of cerebral cortex. While astrocytosis microgliosis both contribute to pathology, contribution gliosis potential factors driving glial activity in human HD cortex less understood. Our study aims identify nuanced indicators which challenging degenerated ganglia, by investigating middle temporal gyrus (MTG), cortical region previously documented demonstrate milder neuronal loss. Immunohistochemistry was conducted on MTG paraffin-embedded tissue microarrays (TMAs) comprising 29 35 neurologically normal cases compare immunoreactivity patterns key astrocytic proteins (glial fibrillary acidic protein, GFAP; inwardly rectifying potassium channel 4.1, Kir4.1; glutamate transporter-1, GLT-1; aquaporin-4, AQP4), microglial (ionised calcium-binding adapter molecule-1, IBA-1; leukocyte antigen (HLA)-DR; transmembrane protein 119, TMEM119; purinergic receptor P2RY12, P2RY12), proliferation (Ki-67; proliferative cell nuclear antigen, PCNA). findings an upregulation GFAP+ expression attributed presence more expressing cells HD, correlated with greater mutant huntingtin (mHTT) deposition. In contrast, Kir4.1, GLT-1, AQP4 levels were unchanged HD. We also increased number IBA-1+ TMEM119+ microglia somal enlargement. IBA-1+, TMEM119+, P2RY12+ reactive immunophenotypes identified evidenced rod-shaped, hypertrophic, dystrophic microglia. cases, contained either Ki-67 or PCNA, whereas astrocytes devoid nuclei. These suggest may be driven supporting hypothesis as feature pathophysiology. altered GFAP profile associated degree mHTT