Scientists discover new role of blood-brain barrier in neuronal function and damage

The role of the blood-brain barrier has long been appreciated because of its precise control over the molecules that enter the nervous system, but little is known about how the cells that form the blood-brain barrier affect the functioning of the nervous syste.

Haghay is the senior author of a study published in the Au.

Disruption of the blood-brain barrier accompanies many neurological diseases, including epilepsy and multiple sclerosis, as well as neurodegenerative diseases of the elderly, such as Alzheimer's disease and Parkinson's diseas.

The discovery introduces a new conceptual approach to finding treatments that can combat the damage caused by neurodegenerative diseases and devising strategies to get drugs across the blood-brain barrier to their target locations in the brai.

Haghighi explains his team's findings this way: Imagine having a gatekeeper checking identities at the door, making sure anyone entering is supposed to be there, while also checking the identities of those entering through the back door and expelling anyone who shouldn't be ther.

Now imagine that the doorman is more than a security check and tells you where to go and what to d.

The research team used fruit fly larvae for the stud.

The research began by focusing on enzymes called metalloproteinases, as they may play a key role in the interactions between glia and neuron.

"We didn't intend to study Notch, but we found that it is a major player in maintaining the blood-brain barrier," Haghely sai.

Under certain conditions, manipulation of Notch signaling affects neuronal activation even when the blood-brain barrier remains intac.

"Because we saw disruption of barrier function, without any apparent barrier leakage, that had an impact on synaptic function, this was a conceptual advance," he said, since no one had previously observed that cells in the barrier itself control neuronal activit.

"We can't yet say what's the cause and what's the effect, but we can say it's not just a correlation of blood-brain barrier disruption in some patients: it's an important correlation with neurodegeneration," Haghely sai.

Their findings open a completely different perspective on developing new therapies aimed at combating impairment of barrier function associated with neurodegenerative disease.

To build on this intriguing premise, Haghighi's team is exploring several direction.

Not much is known about the human versions of Notch and metalloproteinases except that mutations in the human Notch protein can lead to BBB disruption and dementia, and some human metalloproteinases have been found to be involved in neurodegenerative diseases and BBB defects abnormal expressio.

"We hope to be able to work in reverse to fully understand the relationship between the blood-brain barrier and neurodegenerative diseases," Haghighi sai.

Other Buck collaborators include: Mario .
Calderon, Hume Sen, Grant Covey, Jill Farnsworth, Susannah Urian-Benitez, Elie Maksoud and Jordan Shor.

Acknowledgments: This work was funded by the Glenn Foundation, Brain Canada and the National Institutes of Health (R01NS082793 and R01AG057353.

article title

Delta/Notch signaling in glia maintains motor nerve barrier function and synaptic transmission by controlling matrix metalloproteinase expression