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 remains uncertain, and the genetic environment of the midcingulate cortex in the disease has not been investigated.

Utilizing 14 Huntington's disease cases (6 females and 8 males; age range 41-72) split into mood, motor and mixed symptomatology and nine control cases (3 females and 6 males; age range 53-72), we used mRNA sequencing to examine the midcingulate cortex transcriptome in Huntington's disease 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.

Here we show that multiple neuroinflammatory transcripts are overexpressed in the Huntington's disease midcingulate cortex, such as those linked to classical complement, toll-like receptor signaling and AQP4 activity. However, related processes, such as chemokine activity, are downregulated, implying that a complex combination of gain and loss of neuroinflammatory function is occurring.

In summary, neuroinflammation-related transcripts are overrepresented in Huntington's disease cases with motor symptoms compared to mood and mixed. These findings suggest a potentially unique role for the midcingulate cortex in motor-specific neuroinflammatory pathophysiology.