Amine sulfate formation in the central nervous system.

Area of Science:

• Neurochemistry
• Biochemistry
• Pharmacology

Background:

• Sulfated forms of neurotransmitters, including dopamine (DA) and serotonin (5-hydroxytryptamine [5HT]), are found in cerebrospinal fluid (CSF).
• In human CSF, sulfated amines are present in much higher concentrations than their free counterparts.
• Phenol sulfotransferase (PST) is the enzyme responsible for amine sulfation and is detected in human brain tissue.

Purpose of the Study:

• To investigate the significance of amine sulfation in the central nervous system.
• To explore the origin of amine sulfates in CSF, considering both central and peripheral sources.
• To understand the role of PST in regulating neurotransmitter levels.

Main Methods:

• Detection of sulfated amines (DA sulfate, 5HT sulfate) in CSF and plasma.
• Measurement of amine sulfate concentrations in different CSF compartments (lumbar vs. ventricular).
• Investigation of blood-CSF barrier permeability to amine sulfates using animal models (African green monkey).

Main Results:

• Human CSF contains significantly higher levels of sulfated amines than free amines.
• PST in the human brain exhibits high affinity but low capacity for amine sulfation.
• Evidence suggests both central nervous system synthesis and potential plasma contribution to CSF amine sulfates.
• Amine sulfate levels in CSF do not increase from lumbar to ventricular regions, supporting a possible peripheral origin.

Conclusions:

• Amine sulfation is a crucial process for regulating neurotransmitter economy, particularly under basal conditions.
• While the blood-CSF barrier allows some amine sulfates to enter CSF, a significant portion originates within the central nervous system.
• The dual origin of amine sulfates in CSF highlights the complex interplay between peripheral and central mechanisms in neurotransmitter homeostasis.