Rod-shaped Microglia Show Disease and Regional Hippocampal Specificity

Microglial dysfunction is strongly tied to the pathogenesis of neurodegenerative diseases. Remarkable heterogeneity in microglial morphology has been described. The morphologic subtypes include ramified, hypertrophic, dystrophic and rod-shaped microglia. Rod-shaped microglia were first described by Nissl more than 100 years ago; however, little is known about the specific functions of the rod-shaped microglia in neurodegeneration. In this study, we determined if rod-shaped microglia are involved in the process of neurodegeneration, by evaluating the distribution of rod-shaped microglia in the hippocampi of brains with the neuropathology of frontotemporal lobar degeneration with TDP-43 proteinopathy (FTLD-TDP), Alzheimer disease (AD), or no abnormality. We conducted immunohistochemistry with total microglia marker, IBA-1 antibody, followed by semi-quantitation of the density of rod-shaped microglia in the hippocampal sub-regions. This was based on the idea that if rod-shaped microglia contribute to the pathogenesis of neurodegeneration, they would likely exhibit different distribution patterns in the different regions of vulnerability of the hippocampus associated with these different pathologic states. We found that rod-shaped microglia were mainly located in the hippocampal CA1 region, and that the density of rod-shaped microglia in CA1 was higher than the densities in the CA2-4 regions and dentate gyrus, in all groups. Interestingly, there was an increased number of rod-shaped microglia in CA1 in FTLD-TDP as compared to normal brains and those with AD. The densities of rod-shaped microglia were not related to the severity of hippocampal sclerosis in either AD or FTLD-TDP. In addition, the densities of rod-shaped microglia were not related to mutations in GRN or C9ORF72. These data suggest that the rod-shaped microglia have a disease specificity in FTLD and a location specificity in the CA1 sector of the hippocampus.