Blocking cholesterol synthesis impairs acquisition of the classically conditioned eyeblink response

Area of Science:

• Neuroscience
• Biochemistry
• Developmental Biology

Background:

• Smith-Lemli-Opitz syndrome (SLO) is a genetic disorder causing severe intellectual disability due to a defect in cholesterol synthesis.
• The enzyme 7-dehydrocholesterol reductase is crucial for the final step in cholesterol production.
• BM 15.766 (BM) is a chemical agent that inhibits 7-dehydrocholesterol reductase, mimicking SLO's biochemical profile.

Purpose of the Study:

• To investigate the functional impact of impaired cholesterol synthesis on new motor learning.
• To assess the effects of chronic BM treatment on the acquisition of the classically conditioned eyeblink response in rats.

Main Methods:

• Just-weaned rats were administered BM by gavage for four months.
• A subset of BM-treated rats received exogenous cholesterol supplementation during the final two months.
• The acquisition of the eyeblink response was used as a measure of associative learning.

Main Results:

• Rats treated with BM exhibited impaired acquisition of the eyeblink response.
• This learning impairment was observed despite normal responsiveness to conditioned and unconditioned stimuli.
• Exogenous cholesterol administration did not reverse the learning deficits caused by BM.

Conclusions:

• Chronic inhibition of cholesterol synthesis impairs associative learning in young rats.
• The findings suggest that adequate cholesterol levels are essential for normal motor learning processes.
• This study provides insights into the neurological consequences of disrupted cholesterol metabolism, relevant to SLO syndrome.