Microglial morphology as a factor of sex and SNCA gene status

Abstract

Microglia comprise the immune system of the central nervous system. Microglia vary in morphology and in transcriptional and translational profiles. These factors are indicative of function and activation state. The role of the protein alpha-synuclein in neurons is established but remains unclear in microglia. Austin et al. (2006) found that cultured SNCA-knockout microglia display morphologically and translationally distinct profiles as compared to cultured wildtype neurons, but little work has been done to characterize microglial morphology in SNCA-knockout and wildtype mice in vivo. Because Brown et al. (unpublished) found changes in the expression of several genes associated with microglial activation in the hippocampi of SNCA-knockout mice compared to wildtype, the aim of this work was to determine the morphology of microglia in the CA1 of SNCA-knockout and wild-type mice. Confocal microscopy was used to capture high magnification and high resolution images of single microglia from SNCA-knockout and wildtype mice of both sexes (n = 40). Cell morphology was then characterized using Imaris Filament Tracer. SNCA-knockout exhibits a sex-dependent effect on microglial morphology. Microglia from SNCA-knockout female possess significantly more segments, branch points, and terminal points than do cells from wildtype females. These results are suggestive of a hypersurveillant microglial phenotype in SNCA-knockout females. More studies are warranted that compare the phagocytic activity and response to inflammation of microglia in SNCA-knockout and wildtype mice.