Fatty acid synthase expression during peripheral nervous system myelination.

Area of Science:

• Neuroscience
• Molecular Biology
• Biochemistry

Background:

• Fatty acid synthase (FAS) is a key enzyme in fatty acid synthesis.
• Understanding FAS expression is crucial for studying nerve development and myelination.
• The role of FAS in peripheral nervous system (PNS) myelination is not well-defined.

Purpose of the Study:

• To investigate the expression profile of fatty acid synthase (FAS) in rat and mouse sciatic nerves during postnatal development.
• To determine the relationship between FAS expression and peripheral nervous system (PNS) myelination.
• To elucidate the regulatory mechanisms of FAS expression during nerve development.

Main Methods:

• Quantification of FAS activity, protein levels, and mRNA expression in developing rat and mouse sciatic nerves.
• Analysis of FAS expression in a rat demyelination-nerve regeneration model.
• Assessment of FAS expression in the sciatic nerves of 'trembler' mutant mice, a model for PNS dysmyelination.

Main Results:

• FAS activity and protein content in sciatic nerves showed a significant increase from birth, peaking around postnatal day 11, and then declining by day 80.
• FAS mRNA levels paralleled ceramide galactosyl transferase (CGT) mRNA levels during development and regeneration.
• In 'trembler' mutant mice, FAS activity, protein, and mRNA levels were significantly reduced (25% of normal values), indicating impaired myelination.

Conclusions:

• Sciatic nerve FAS expression is closely linked to the peripheral nervous system (PNS) myelination process.
• The primary regulation of FAS during sciatic nerve development occurs at the gene expression level.
• FAS plays a significant role in the synthesis of lipids required for myelin formation.