Related Experiment Video
Updated: Aug 24, 2026
Dendritic Spine Quantification Using an Automatic Three-Dimensional Neuron Reconstruction Software
Published on: September 27, 2024
Dendritic spine pathology and deficits in experience-dependent dendritic plasticity in R6/1 Huntington's disease
Tara L Spires1, Helen E Grote, Sylvia Garry
1University Laboratory of Physiology, University of Oxford, Parks Road, Oxford, OX1 3PT, UK. tspires@partners.org
Insights
Huntington's disease (HD) causes dendritic spine loss in R6/1 mice, impacting brain connectivity. Environmental enrichment failed to reverse this neurodegenerative pathology in HD mice.
Area of Science:
- Neuroscience
- Genetics
- Pathology
Background:
- Huntington's disease (HD) is a fatal neurodegenerative disorder linked to CAG repeat expansion in the huntingtin gene.
- Dendritic abnormalities are observed in human HD patients and mouse models, suggesting disrupted neuronal connectivity.
Purpose of the Study:
- To investigate dendrite and spine pathology in the R6/1 mouse model of Huntington's disease.
- To examine the impact of environmental enrichment on dendrite pathology in HD.
Main Methods:
- Utilized Golgi-impregnation of brain tissue from R6/1 HD mice and wild-type controls.
- Analyzed dendritic spine density, length, and morphology in striatal and cortical neurons.
- Assessed the effects of environmental enrichment from 1 to 8 months of age.
Main Results:
- Symptomatic R6/1 mice showed reduced dendritic spine density and length in medium spiny and pyramidal neurons.
- A specific decrease in bifurcated dendritic spines was noted on basal dendrites of cortical neurons.
- Environmental enrichment did not improve spine pathology in HD mice, despite increasing spine density in wild-type mice.
Conclusions:
- Dendritic spine pathology in R6/1 mice mirrors human HD, indicating disrupted neural connectivity in the striatum and cortex.
- The Huntington's disease mutation impairs the brain's ability to respond to environmental enrichment, affecting neuronal plasticity.
Abstract:
Huntington's disease (HD) is a fatal neurodegenerative disease caused by a CAG repeat expansion coding for an expanded polyglutamine tract in the huntingtin protein. Dendritic abnormalities occur in human HD patients and in several transgenic mouse models of the disease. In this study, we examine, for the first time, dendrite and spine pathology in the R6/1 mouse model of HD, which mimics neurodegeneration seen in human HD. Enriching the environment of HD transgenic mice delays the onset of symptoms, so we also examine the effects of enrichment on dendrite pathology. Golgi-impregnated tissue from symptomatic R6/1 HD mice reveals a decrease in dendritic spine density and dendritic spine length in striatal medium spiny neurons and cortical pyramidal neurons. HD also causes a specific reduction in the proportion of bifurcated dendritic spines on basal dendrites of cortical pyramidal neurons. No differences in soma size, recurving distal dendrites, or dendritic branching were observed. Although home-cage environmental enrichment from 1 to 8 months of age increases spine density in wild-type mice, it has no effect on the spine pathology in HD mice. These results show that dendritic spine pathology in R6/1 HD mice resembles degenerative changes seen in human HD and in other transgenic mouse models of the disease. We thus provide further evidence that the HD mutation disrupts the connectivity in both neostriatum and cerebral cortex, which will contribute to motor and cognitive disease symptoms. Furthermore, we demonstrate that Huntington's disease pathology interferes with the normal plastic response of dendritic spines to environmental enrichment.
