Exploration of the Genetic Neuroinflammatory Environment in the Human Midcingulate Cortex in Huntington's Disease
Despite progress, the pathophysiology involving neuroinflammation in Huntington's disease (HD) remains uncertain, and the genetic environment of the HD midcingulate cortex (MCC) has not been investigated. This study shows that multiple neuroinflammatory processes are overexpressed in the HD MCC, such as classical complement, toll-like receptor signaling and AQP4 activity. However, related processes such as chemokine activity are downregulated, implying a complex combination of gain and loss of neuroinflammatory function is occurring. Utilizing 14 HD cases split into mood, motor and mixed symptomatology, we used mRNA sequencing to examine the MCC transcriptome in HD and NanoString analysis to validate the differentially expressed transcripts. These genes underwent bioanalysis including gene ontology enrichment, protein-protein interaction and cell-type enrichment analysis. Neuroinflammation-related transcripts were overrepresented in HD cases with motor symptoms compared to mood and mixed, potentially indicating a unique role for the MCC in motor-specific neuroinflammatory pathophysiology.