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Sergey KasparovThe role of astrocytes in control of breathing : Studies using cell-specific viral gene expression.

Abstract :


For a number of years we have been using viral vector to deliver, and more recently knock-down genes in specific sub-sets of cells in the brain. This approach has great advantages for many neuroscience applications compared to conventional germ-line transgenesis. In the first part of this talk I will briefly review the basic principles of cell-specific viral transgenesis, strategies used to increase the potency of transgene expression and the approach we use for gene knock down. In the second part of the talk I will go through the recent data which was obtained in our collaborative project with Alex Gourine’s lab at UCL, which implicates ventral medullary astrocytes in central chemosensitivity, the most important mechanism regulating respiration in mammals. We used in vitro and in vivo preparations and novel imaging and opto-genetic tools expressed using viral vectors and found that astrocytes in the ventral regions of the medulla oblongata are highly sensitive to changes in pH. Astrocytes enwrapping penetrating arteries respond to acidification with [Ca2+]i,-mediated release of ATP which induces increases in breathing. This can be mimicked by optogenetic activation of ventral medullary astrocytes. These data directly demonstrate an essential role for glial cells in a fundamental physiological reflex.
 

Sergey Kasparov has pioneered research based on the use of cell-specific viral gene expression and dedicates considerable efforts to the development of new molecular and imaging techniques. He has published over 60 research papers in peer-reviewed journals.

 

Selected publications

Benzekhroufa K, Liu B, Tang F, Teschemacher AG, & Kasparov S (2009a). Adenoviral vectors for highly selective gene expression in central serotonergic neurons reveal quantal characteristics of serotonin release in the rat brain. BMC Biotechnol 9, 23.
 
Benzekhroufa K, Liu BH, Teschemacher AG, & Kasparov S (2009b). Targeting central serotonergic neurons with lentiviral vectors based on transcriptional amplification strategy. Gene Therapy 16, 681-688.

Duale H, Waki H, Howorth P, Kasparov S, Teschemacher AG, & Paton JFR (2007). Restraining infulence of A2 neurones in chronic control of blood pressure in SHR. Cardiovascular Research 76, 184-193.