(174) RNA-Seq investigations of human post-mortem trigeminal ganglia with a perspective on headache and migraine

Chronic headache and migraine are debilitating conditions that affect millions of Americans, yet are poorly understood. Recent next-gen sequencing methodologies have greatly expanded the capabilities for probing molecular-genetic mechanisms of headache and migraine. Specifically, RNA-Seq provides the opportunity to examine and quantitatively measure all of the transcripts in a particular tissue, such as the trigeminal ganglion or dura mater, which are hypothesized to be sites of onset and regulatory processes in headache. Post-mortem measurements of gene expression in human trigeminal sub-regions were performed by RNA-Seq, and sequence alignment was made to human, viral, and bacterial genomic targets. Herpes simplex virus 1 (HSV-1) transcripts were detected in several ganglia and validated by measurement of HSV-1 antibodies in blood using the luciferase immunoprecipitation assay. The number of HSV-1 reads in transcriptomically positive ganglia correlated with HSV-1 antibody levels in respective whole blood samples. The differential expression patterns observed within anatomically distinct sub-regions of the excised ganglion demonstrate the diversity of trigeminal gene expression and highlight the neuronal trigeminal transcriptome. Characterization of migraine susceptibility genes expressed in the trigeminal ganglion revealed three patterns of expression: CNS, PNS, and broad spectrum. Of the genes broadly expressed throughout the body, 40% showed a strong arterial signature, emphasizing the blood vessel component of the trigeminovascular system. These data also provide a comprehensive framework for evaluation of many of the parameters, such as RNA-Seq quality control, next-gen sequencing methodologies, and downstream analyses, that impinge on post-mortem studies of pathological headache, migraine conditions, and the trigeminal ganglion.