Probable Basis of Altered BBB Nutrient Transport in the Offspring of Severely Hypothyroid Dams

Area of Science:

• Neuroscience
• Endocrinology
• Biochemistry

Background:

• Maternal exposure to antithyroid compounds during gestation and lactation can impact offspring development.
• Previous observations indicated increased nutrient transport across the blood-brain barrier (BBB) in offspring of mothers exposed to 6-n-propyl-2-thiouracil (PTU).

Purpose of the Study:

• To investigate the underlying mechanisms of altered BBB nutrient transport in offspring exposed to PTU.
• To determine the kinetics of 2-deoxy-D-glucose transport across the BBB in situ.
• To assess the fluidity and fatty acid profile of brain microvessel plasma membranes.

Main Methods:

• In situ assessment of 2-deoxy-D-glucose transport kinetics across the BBB.
• Measurement of plasma membrane fluidity in isolated brain microvessels.
• Analysis of the fatty acid composition of brain microvessel plasma membranes.

Main Results:

• Offspring of PTU-fed dams exhibited a markedly increased maximal transport capacity (Tmax app) for 2-deoxy-D-glucose across the BBB.
• A significant increase in the fluidity of brain microvessel plasma membranes (BMVPM) was observed.
• This increased fluidity correlated with a higher unsaturation index and polyunsaturated fatty acid content in BMVPMs.

Conclusions:

• The study suggests that maternal hypothyroidism induced by PTU alters BBB nutrient transport in offspring.
• Changes in the membrane microenvironment, specifically increased fluidity and altered fatty acid composition, likely contribute to enhanced BBB transport.
• These alterations may involve modifications in the kinetics of existing transporters or the exposure of previously latent transporters.