Glucocorticoid receptor antagonist CORT113176 attenuates motor and neuropathological symptoms of Huntington's disease in R6/2 mice

In this study, we evaluated the efficacy of the selective GR antagonist CORT113176 in the commonly used R6/2 mouse model. In male mice, CORT113176 treatment significantly delayed the loss of grip strength, the development of hindlimb clasping, gait abnormalities, and the occurrence of epileptic seizures. CORT113176 treatment delayed loss of DARPP-32 immunoreactivity in the dorsolateral striatum. It also restored HD-related parameters including astrocyte markers in both the dorsolateral striatum and the hippocampus, and microglia markers in the hippocampus. This suggests that CORT113176 has both cell-type and brain region-specific effects. CORT113176 delayed the formation of mHtt aggregates in the striatum and the hippocampus. In female mice, we did not observe major effects of CORT113176 treatment on HD-related symptoms, with the exception of the anti-epileptic effects. We conclude that CORT113176 effectively delays several key symptoms related to the HD phenotype in male R6/2 mice and believe that GR antagonism may be a possible treatment option.PMID:38216109 | DOI:10.1016/j.expneurol.2024.114675
Source: Experimental Neurology - Category: Neurology Authors: Source Type: research