Background Currently, the concept of neuroinflammation includes inflammation associated with neurodegenerative diseases, in which there is little or no infiltration of blood-derived immune cells into the brain. However, the roles of brain-resident and peripheral immune cells in inflammatory settings are poorly understood, and neuroinflammation has not been well investigated in either Huntington’s disease (HD) patients or equivalent preclinical models.
Aims This project aims to characterise the neuroinflammatory processes occurring in the R6/2 mouse model of HD over the time-course of the disease, using a number of molecular and cellular techniques in combination with in vivo imaging modalities (magnetic resonance spectroscopy [MRS] and magnetic resonance imaging [MRI]).
Methods The R6/2 mouse expresses exon 1 of the human HTT gene, containing ˜180 CAGs. To begin undertaking a time-course analysis of the disease, immunohistochemistry (IHC) and western blotting were used in R6/2 and wild type (WT) mice between the ages of four- (pre-symptomatic) and 14-weeks-old (late-stage disease) to assess the neuroinflammatory processes in HD.
Results Protocol optimisations to assess microglia and astrocytes (via their hallmark proteins IBA1 and GFAP respectively), two key cell types that mediate neuroinflammatory processes, have been performed for both western blotting and IHC. Subsequently, following their assessment in R6/2 mice, microglia and astrocytes were altered in terms of their reactivity, morphology and densities in comparison to WT controls.
Conclusions The results of these investigations have begun to reveal changes in key neuroinflammatory cell types throughout the time-course of HD. In vivo imaging approaches and other molecular and cellular assessments will now be used to enable a more detailed characterisation of neuroinflammation in HD, and to identify robust, translational markers by which to track disease progression.
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