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Spinal Cord Electrophysiology

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Published on: January 19, 2010

CNS synaptogenesis promoted by glia-derived cholesterol.

D H Mauch¹, K Nägler, S Schumacher

¹Synapse Group and, Protein Chemistry Group, Max-Delbrück-Center for Molecular Medicine, D-13092 Berlin, Germany.

Science (New York, N.Y.)

|November 10, 2001

Summary

Glia provide essential cholesterol via lipoproteins to support central nervous system (CNS) synaptogenesis. Cholesterol availability limits synapse development, explaining developmental delays and neurological disorders.

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Area of Science:

Neuroscience
Cell Biology
Biochemistry

Background:

Synaptogenesis in the central nervous system (CNS) involves complex molecular mechanisms that remain largely unknown.
A previously identified glia-derived factor was shown to significantly enhance synapse development in cultured CNS neurons.

Purpose of the Study:

To identify the glia-derived factor that promotes synapse development.
To elucidate the role of cholesterol and lipoproteins in CNS synaptogenesis.

Main Methods:

Identification of the glia-derived factor using biochemical analysis.
Culturing of purified CNS neurons to study synapse formation.
Assessment of cholesterol requirements for synapse development.

Main Results:

The identified glia-derived factor is cholesterol complexed with apolipoprotein E-containing lipoproteins.
While CNS neurons produce sufficient cholesterol for survival and growth, mature synapse formation requires additional cholesterol supplied by glia.
Cholesterol availability was identified as a limiting factor for CNS synaptogenesis.

Conclusions:

Cholesterol supplied by glia, carried in apolipoprotein E lipoproteins, is crucial for central nervous system synaptogenesis.
The findings suggest that cholesterol availability regulates the rate and extent of synapse formation.
This mechanism may explain the timing of CNS synaptogenesis relative to glial differentiation and the neurobehavioral consequences of cholesterol homeostasis defects.