Ari Barzilai (Neurobiology Department, Life Sciences Faculty, Tel Aviv University)

The Bernstein Center Freiburg

Bernstein Seminar

Ari Barzilai

Neurobiology Department
Life Sciences Faculty
Tel Aviv University, Israel

 

The role of the DNA damage response in the functionality of the neuro-glio-vascular unit

Abstract:
A hallmark of neurodegenerative diseases is impairment of certain aspects of "brain functionality", which is defined as the total input and output of the brain's neural circuits and networks. A given neurodegenerative disorder is characterized by affected network organization and topology, cell numbers, cellular functionality, and the interactions between neural circuits. Neuroscientists generally view neurodegenerative disorders as diseases of neuronal cells; however, recent advances suggest a role for glial cells and an impaired vascular system in the etiology of certain neurodegenerative diseases. It is now clear that brain pathology is, to a very great extent, pathology of neurons, glia and the vascular system as these determine the degree of neuronal death as well as the outcome and scale of the neurological deficit. To validate the role of neuro-glio-vasuclar unit in the etiology in genome stability disorders I will describe various aspects of neural and glial cell fate and the vascular system in genomic instability disorders including ataxia telangiectasia (A-T) and Nijmegen breakage syndrome (NBS). We found that specific deletion of the NBS1 gene in the CNS severely hampers glial cell functionality. In addition, we discovered that Atm deficiency led to retinal as well cerebellar vascular abnormalities. In addition, we found that Atm protein deficiency, which in humans leads to progressive motor impairment, leads to a reduced synchronization persistence compared to wild type synchronization, after chemically imposed DNA damage. These results suggest that impaired neural network activity as well as reduced glial cell functionality, hampered vascularization and astrocyte-endothelial cell interactions in the central nervous system play an important role in the etiology genome stability disorders and may underlie or aggravate neurodegeneration.

Host: Noah Levine-Small