In the work published in the Faseb Journal, researchers from the Institute for Organic Synthesis and Photoreactivity and the Institute for the Study of Nanostructured Materials of the National Research Council of Bologna, in collaboration with the University of Vanderbilt, the University of Bari, the University of Bologna and with the Centre of Excellence for Nanoscale BioPhotonics of the University of Adelaide (ARC CNBP) have shown that a flash of infrared laser light of only 8 thousandths of a second can modulate the function of astrocytes. The main activity of astrocytes is to act as sensors and controllers of the composition and chemophysical features of the extracellular brain space. To do this, astrocytes continuously transport and redistribute ions and water and activate intracellular calcium signals. These dynamics are fundamental for brain functions such as synapses, sleep, memory. The alteration of calcium signals and water transport in astrocytes is the cause of pathologies such as edema, ischemia, stroke and epilepsy.
The study shows that it is possible to activate the dynamics of astrocytes, in real time, in very small spaces (millionths of a millimeter), simply by using the infrared light stimulus and without the need to use genetic modifications or molecules that make cells sensitive to light , as instead happens in optogenetics or chemogenetics. "An important step to clarify the function of astrocytes in the brain, but also for the development of frontier therapeutic approaches for incurable diseases, characterized by impaired transport of water and ions, such as cerebral edema", says the coordinator of the study Valentina Benfenati, first researcher of Cnr-Isof.
The analysis was possible using the infrared nerve stimulation (Ins) technique, developed by Anita Mahadevan-Jansen of the University of Vanderbilt, which until now had only been used to excite or inhibit neurons.
This work is also the first demonstration of a technology that is capable of modulating the flow of water through the plasma membrane of cells. "To date, in fact, there are no drugs or methods capable of controlling the function of channel proteins that permeate water, the so-called aquaporins", underlines Grazia Paola Nicchia, professor at the Department of Biosciences, biotechnology and biopharmaceuticals of the University of Bari Aldo Moro and researcher associated with Cnr-Isof. The work shows that infrared light activates the calcium channel, called Transient Receptor Potential Vanilloid 4 (TRPV4). "A channel that activates in response to various stimuli such as pain, high temperatures or osmotic stress", adds Marco Caprini professor at the Pharmacy and biotechnology department of the University of Bologna and associate researcher at Cnr-Ismn.
The research was supported by the Astronir research project funded by the Air Force Office of Scientific Research, coordinated by Cnr-Isof and also by the European Olimpia project, coordinated by Cnr-Ismn.
Rome, 27th april 2020
Who: National Research Council: Institute for Organic Synthesis and Photoreactivity (Cnr-Isof) of Bologna, Institute for the Study of Nanostructured Materials, Cnr-Ismn, in collaboration with Vanderbilt Biophotonics Center, Vanderbilt University; University of Bari Aldo Moro, Dept of Bioscience, Biotechnology and Biopharmaceutics, University of Bologna, Department of Pharmacy and Biotechnology, FaBit, Bologna, Italy; Center for Nanoscale BioPhotonics, University of Adelaide, Adelaide, Australia
What: Identification of the strategic functions of astrocytes in identifying the causes of patholige such as: cerebral edema, ischemia, stroke and epilepsy: Stimulation of water and calcium dynamics in astrocytes with pulsed infrared light; Phaseb Journal, Wiley, IF 5.3, https://faseb.onlinelibrary.wiley.com/doi/full/10.1096/fj.201903049R
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