Sex-dependent impaired locomotion and motor coordination in the HdhQ200/200 mouse model of Huntington’s Disease.

Sex-dependent impaired locomotion and motor coordination in the HdhQ200/200 mouse model of Huntington’s Disease.

Publication date: Sep 06, 2019

Huntington’s Disease (HD) is a fatal neurodegenerative disease characterized by severe loss of medium spiny neuron (MSN) function and striatal-dependent behaviors. We report that female HdhQ200/200 mice display an earlier onset and more robust deterioration in spontaneous locomotion and motor coordination measured at 8 months of age compared to male HdhQ200/200 mice. Remarkably, HdhQ200/200 mice of both sexes exhibit comparable impaired spontaneous locomotion and motor coordination at 10 months of age and reach moribund stage by 12 months of age, demonstrating reduced life span in this model system. Histopathological analysis revealed enhanced mutant huntingtin protein aggregation in male HdhQ200/200 striatal tissue at 8 months of age compared to female HdhQ200/200. Functional analysis of calcium dynamics in MSNs of female HdhQ200/200 mice using GCaMP6m imaging revealed elevated responses to excitatory cortical-striatal stimulation suggesting increased MSN excitability. Although there was no down-regulation of the expression of common HD biomarkers (DARPP-32, enkephalin and CBR), we measured a sex-dependent reduction of the astrocytic glutamate transporter, GLT-1, in female HdhQ200/200 mice that was not detected in male HdhQ200/200 mice when compared to respective wild-type littermates. Our study outlines a sex-dependent rapid deterioration of striatal-dependent behaviors occurring in the HdhQ200/200 mouse line that does not involve alterations in the expression of common HD biomarkers and yet includes impaired MSN function.

Cao, J.K., Viray, K., Zweifel, L., and Stella, N. Sex-dependent impaired locomotion and motor coordination in the HdhQ200/200 mouse model of Huntington’s Disease. 06670. 2019 Neurobiol Dis.

Concepts Keywords
Astrocytic Brain
Biomarkers Imaging
Calcium Branches of biology
Cortical Basal ganglia
Enkephalin Addiction
Excitatory Medium spiny neuron
Glutamate Neurons
Histopathological PPP1R1B
Huntingtin Huntingtin
Huntington Biomarker
Medium Spiny Neuron Striatum
Mice Animal locomotion
Motor Coordination
MSN
Mutant
Neurodegenerative
Striatal
Wild Type

Semantics

Type Source Name
gene UNIPROT NOP53
gene UNIPROT CBR1
gene UNIPROT PPP1R1B
drug DRUGBANK Calcium
gene UNIPROT HTT
disease DOID neurodegenerative disease
gene UNIPROT MSN
disease MESH neurodegenerative disease
gene UNIPROT PLXNA3

Original Article

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