Characterization of a target-derived neuronal cholinergic differentiation factor

Area of Science:

• Neuroscience
• Developmental Biology
• Cell Biology

Background:

• Sympathetic nerves in rat sweat glands change neurotransmitter expression during development.
• This switch involves a transition from noradrenergic to cholinergic and peptidergic phenotypes.
• Cultured sympathetic neurons treated with sweat gland extracts mimic these in vivo developmental changes.

Purpose of the Study:

• To investigate the factors responsible for the developmental neurotransmitter switch in rat sweat gland innervation.
• To characterize the properties of the identified sweat gland differentiation factor.
• To determine if this factor is related to known cholinergic differentiation factors.

Main Methods:

• Culture of sympathetic neurons with rat sweat gland extracts.
• Assays for neurotransmitter-related enzyme activity (e.g., choline acetyltransferase) and neuropeptide expression.
• Biochemical characterization of the active component in sweat gland extracts (heat lability, trypsin sensitivity, binding properties).
• Immunoprecipitation studies using antisera against known differentiation factors.

Main Results:

• Sweat gland extracts induced choline acetyltransferase activity and vasoactive intestinal peptide expression in cultured neurons.
• Extracts reduced catecholaminergic properties and neuropeptide Y expression in a dose-dependent manner.
• The active differentiation factor is a heat-labile, trypsin-sensitive, acidic protein, distinct from CDF/LIF.

Conclusions:

• A novel sweat gland-derived factor mediates the target-induced neurotransmitter phenotype switch in sympathetic neurons.
• This factor is crucial for the developmental regulation of sympathetic function in sweat glands.
• The identified factor is a strong candidate for the in vivo mediator of this neuroplasticity.