Cortical cholesterol deficit and reduced network excitability in ApoE-Deficient mice

Area of Science:

• Neuroscience
• Biochemistry
• Genetics

Background:

• Apolipoprotein E (ApoE) is crucial for cholesterol transport and a major genetic risk factor for Alzheimer's disease.
• ApoE deficiency elevates circulating cholesterol but its brain-specific effects on homeostasis and function are not fully understood.

Purpose of the Study:

• To investigate the impact of ApoE deficiency on systemic and brain cholesterol levels.
• To assess synaptic integrity and cortical network excitability in ApoE-deficient mice.

Main Methods:

• Comparison of ApoE knockout (ApoE-/-) and wild-type (WT) mice.
• Measurement of serum and brain cholesterol levels.
• Analysis of synaptic protein expression (SYP, PSD-95).
• Electrocorticography (ECoG) to assess cortical network activity and excitability.

Main Results:

• ApoE-/- mice exhibited elevated serum cholesterol but reduced cortical cholesterol.
• Synaptophysin and PSD-95 levels were decreased in ApoE-/- mice.
• Cortical network activity was reduced, with attenuated responses to pharmacological excitation.

Conclusions:

• ApoE deficiency causes a complex disruption: high peripheral cholesterol, low cortical cholesterol, synaptic loss, and reduced cortical excitability.
• Impaired brain cholesterol homeostasis in ApoE deficiency is linked to altered synaptic network function.