An ultrastructural analysis of microglial morphological changes in response to manipulation of RNA binding protein TIA1 in the P301S mouse model of Alzheimer's disease
Nicoletti, Nicholas William
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Microglia are essential to the brain’s innate immune response and play a vital role in neuropathology related to tauopathies. Understanding how microglia change in response to differential expression of RNA binding protein T-cell intracellular antigen 1 (TIA1) will lend insight to microglial function in tauopathy. In preliminary studies our laboratory has shown that decreasing the expression of TIA1 has an inverse and dose dependent effect on activated microglial density in the dentate gyrus of the P301S mouse (PhD Candidate Chelsey LeBlang, 2018). Here, we utilized serial sectioning electron microscopy to define whether this relationship between TIA1 level and microglia remains consistent in the hilus and granule cell layer (GCL) of the dentate gyrus. Our analyses of microglial volume and microglial interactions within the neuropil have yielded four conclusions. First, the hilus, but not the GCL, exhibited a significant decrease in microglial volume per volume of tissue with the knock out and heterozygous expression of TIA1. Second, the number of appositions on microglia steadily increased on AT8+ and AT8- presynaptic and postsynaptic appositions in the hilus with decreasing TIA1 expression. Third, with the exception of one AT8- somatic apposition, the surface area of microglia apposing AT8+ somata is greater than any other structure and exhibits a dose dependent decrease with decreasing TIA1 expression. Fourth, in the GCL there is a larger fractional surface area of AT8- presynaptic and AT8+ postsynaptic structures when compared to their respective synaptic counterparts. Though not entirely consistent with previous data, this study has important implications for microglial function in tauopathy and related diseases.