![]() The disease manifests with a triad of clinical signs, including uncontrollable movements (chorea) later replaced by akinesia, psychiatric symptoms such as depression, and cognitive impairment culminating in dementia ( Tabrizi et al., 2020). Huntington’s disease (HD) is a hereditary movement disorder that typically starts in midlife and is inevitably lethal within 10–20 years after onset. Taken together, our findings point to differential molecular changes in cortical interneuron types of HD mice. In contrast to the R6/2 model, heterozygous zQ175DN knock-in HD mice do not show any significant histological changes in cortical cell types at the age of 12 months, apart from the presence of mHTT inclusions, which are abundant in pyramidal neurons and rare in interneurons. Furthermore, we demonstrate progressive accumulation of mutant Huntingtin (mHTT) inclusion bodies in interneurons, which occurs faster in SST and VIP compared to PV cells. We also observe a reduction in cell body size for all three interneuron populations. However, genetic labeling reveals unchanged cell numbers for all the interneuron types, pointing to molecular marker loss in the absence of cell death. In R6/2 mice, we find a selective reduction in SST and VIP, but not PV-positive cells. Here, we use a combination of immunostaining and genetic tracing to investigate histological changes in three major cortical interneuron types - parvalbumin (PV), somatostatin (SST), and vasoactive intestinal peptide (VIP) interneurons - in the R6/2 and zQ175DN mouse models of HD. In the cortex, glutamatergic pyramidal neurons are known to be severely affected by the disease, but the involvement of GABAergic interneurons remains unclear. HD causes neurodegeneration particularly in the basal ganglia and neocortex. Huntington’s disease (HD) is a debilitating hereditary motor disorder caused by an expansion of the CAG triplet repeat in the Huntingtin gene. 3Center for Anatomy, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.2Molecular Neurodegeneration Group, Max Planck Institute for Biological Intelligence, Martinsried, Germany. ![]() 1Department of Molecules–Signaling–Development, Max Planck Institute for Biological Intelligence, Martinsried, Germany.Kerstin Voelkl 1,2 Elena Katharina Schulz-Trieglaff 1 Rüdiger Klein 1 Irina Dudanova 1,2,3* ![]()
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