Microstructural changes observed with DKI in a transgenic Huntington rat model: evidence for abnormal...

Area of Science:

• Neuroscience
• Biomedical Imaging
• Genetics

Background:

• Huntington Disease (HD) is a fatal neurodegenerative disorder caused by a mutation in the Huntington gene.
• While typically diagnosed mid-life, HD's origins may lie in early brain development.
• Studying early-onset changes is crucial for understanding HD progression.

Purpose of the Study:

• To investigate brain microstructure alterations in developing transgenic HD rat pups.
• To utilize in vivo Diffusion Kurtosis Imaging (DKI) to detect these changes.
• To validate DKI findings with histological analysis.

Main Methods:

• In vivo Diffusion Kurtosis Imaging (DKI) was performed on transgenic HD rat pups at postnatal days 15 (P15) and 30 (P30).
• Specific brain regions (caudate putamen, cortex, corpus callosum, external capsule, anterior commissure) were examined.
• DKI results were corroborated using myelin basic protein immunohistochemistry.

Main Results:

• At P15, increased mean (MD) and radial (RD) diffusivity were observed in the cortex of HD rat pups.
• At P30, decreased axial kurtosis (AK) was found in the caudate putamen of HD pups.
• Histology confirmed reduced and less ordered myelin fibers in HD rat pups, aligning with DKI findings.

Conclusions:

• Neuronal development differs in young transgenic HD rat pups compared to controls.
• The presence of mutant huntingtin significantly influences postnatal brain development.
• DKI is a powerful tool for assessing microstructural changes and developmental alterations in early-stage HD models.