A new study providing mechanistic insight into the biology of barrier function and glia-neuron interactions published in the Proceedings of the National Academy of Sciences (PNAS) explains the link between Delta/Notch signaling in sub perineurial glia (SPG) and the regulation of nerve ensheathment and neurotransmitter release at the Drosophila neuromuscular junction (NMJ). It showed that the SPG, the counterpart of the endothelial layer in the vertebrate blood-brain barrier, forms the key cellular layer that is critical for axonal ensheathment and the blood-brain barrier in Drosophila. The researchers observed that in fruit flies, signals originating in the cells of the barrier played a direct role in controlling what happened in the nerve cells the barrier was protecting.

The finding introduced a new conceptual approach to looking for therapies that could counter damage caused by neurodegenerative diseases and devise strategies to get drugs past the blood-brain barrier to target sites in the brain. Dr. Haghighi, the lead author of the study, stated that his team’s findings can be explained as such: Imagine that there is a gatekeeper at a door that checks IDs and ensures that anyone entering is supposed to be there, and also checks the ID of those who entered through a back door and kicks out anyone not supposed to be there. That is the job of the blood-brain barrier.

Now imagine that, beyond just being a security check, the gatekeeper also gives out directions about where to go and what to do. That was the second function that was revealed in the study. The team used fruit fly larvae for their study as fruit flies do not have the complexity of vertebrate blood-brain barriers and many of the properties are the same. Also, the key cells that provide a barrier for neurons in fruit flies are specialized glia which are similar to the specialized endothelial cells of the blood-brain barrier in higher vertebrates, including humans.

The investigation began with a focus on enzymes called metalloproteinases, a potential regulator of interactions between glia and neurons. Using a genetic approach, the team identified a pathway known as Notch signaling. Notch is found in both fruit flies and humans. It is associated with human diseases of vasculature, dementia, and stroke. The team discovered that Notch signaling in the glia regulates the overall structure of the barrier. Dr. Haghighi stated that when the signal is blocked, not only is barrier function impaired but the fundamental work of the nervous system is affected, including neurotransmitter release and muscle contractions. However, he explained that under certain conditions, manipulation of Notch signaling affected how neurons were fired, even though the blood-brain barrier remained intact. 

(Source: https://theprint.in/health/researchers-find-new-functions-for-blood-brain-barrier-in-neuron-function-and-damage/1085650/ )