Impaired Resting-State Functional Connectivity in Cerebral Autosomal-Dominant Arteriopathy, Subcortical Infarcts, and...

Area of Science:

• Neuroscience
• Genetics
• Vascular Biology

Background:

• Cerebral autosomal-dominant arteriopathy, subcortical infarcts, and leukoencephalopathy (CADASIL) is a common inherited cause of cerebral small vessel disease.
• Currently, no effective therapies exist to halt or reverse CADASIL progression.

Purpose of the Study:

• To investigate white matter tract integrity in a mouse model of CADASIL (Notch3R169C mice).
• To assess the impact of a corpus callosum lesion on brain connectivity and behavior.
• To evaluate the neuroprotective potential of tocotrienol in this CADASIL model.

Main Methods:

• Utilized optical resting-state functional connectivity imaging in Notch3R169C mutant and wild-type mice.
• Conducted behavioral tests (grid walk) to assess motor function.
• Introduced focal white matter lesions and administered tocotrienol treatment.

Main Results:

• Notch3R169C mice exhibited significantly reduced functional connectivity and poorer performance on the grid walk test compared to controls.
• Corpus callosum lesions similarly impaired connectivity and behavior in both genotypes.
• Tocotrienol treatment did not demonstrate any protective effects on the measured outcomes.

Conclusions:

• The Notch3R169C mouse model displays impaired functional connectivity and motor deficits, mirroring CADASIL.
• These findings establish relevant outcome measures for future therapeutic interventions in CADASIL research.