Upregulation of histone deacetylase 2 in laser capture nigral microglia in Parkinson's disease

Histone deacetylase (HDAC) inhibitors have been widely reported to have considerable therapeutic potential in a host of neurodegenerative diseases. However, HDAC inhibitor selectivity and specificity in specific cell classes have been a source of much debate. To address the role of HDAC2 in specific cell classes, and in disease, we examined glial protein and mRNA levels in the substantia nigra (SN) of Parkinson's disease (PD) and normal controls (NCs) by immunohistochemistry and laser captured microdissection followed by quantitative real time polymerase chain reaction. Differential expression analysis in immunohistochemically defined laser capture microglia revealed significant upregulation of HDAC2 in the PD SN compared to NC subjects. Complementary in vivo evidence reveals significant upregulation of HDAC2 protein levels in PD SN microglia compared to NC subjects. Correspondingly, human immortalized telencephalic/mesencephalic microglial cells reveal significant upregulation of HDAC2 in the presence of the potent microglial activator lipopolysaccharide. These data provide evidence that selective inhibition of HDAC2 in PD SN microglia could be a promising approach to treat microglial-initiated nigral dopaminergic neuronal cell loss in PD.