Developmentally Regulated Expression and Activity of Sulphotransferases in the Rat Choroid Plexuses

During development, entry of any substances from the circulation into the brain is tightly regulated by a series of blood-brain interfaces. Notably, the choroid plexuses, which form the blood-cerebrospinal fluid barrier, serve as a key interface for molecular exchange in early life. Control mechanisms within the choroid plexuses include efflux transporters and conjugating enzymes, such as glutathione S-transferases and UDP-glucuronosyltransferases, which have been shown to play key roles in safeguarding the developing brain. Sulphotransferases are another family of conjugating enzymes reported to be highly expressed in the choroid plexus in humans and rats during development. However, their activity and functional significance in the central nervous system remain poorly understood. In the present study, sulphotransferase activity was measured in the lateral and fourth ventricle choroid plexus from rats at embryonic Day 19 and postnatal Day (P)1, 3, 8 and 30. Activity was correlated with expression of isoenzymes by RT-qPCR. Inhibition studies were performed by co-incubating a prototypical sulphotransferase substrate with a potential substrate or inhibitor. Finally, assays in freshly isolated live tissue were conducted to assess sulphoconjugation under more physiologically relevant conditions. Results showed that both sulphotransferase activity and expression of Sult1a1 in the choroid plexus were markedly increased at P1 to P3. This distinct temporal pattern suggests age- and tissue-specific roles of choroidal sulphotransferase activity during the early postnatal period. Interactions with xenobiotics and neuroendocrine factors further suggest that these enzymes may contribute to multiple processes during this critical window, including protection against potentially harmful substances and regulation of neurotransmitters. Furthermore, the observed modulation of choroidal sulphotransferase activity by various exogenous substances suggests that developmental exposure could disrupt sulphotransferase-mediated biological processes, with potential consequences for normal neurodevelopment.