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Prof. Andjus is the founder and current Head of the Centre for laser microscopy, University of Belgrade Faculty of Biology and president of the Serbian Brain Council. In 1981 he graduated in Molecular Biology and Physiology at the University of Belgrade and obtained his MSc and PhD in Biophysics at the same University. He was trained in the Institute for Biological Physics - Pushchino (USSR), MBL - Woods Hole (USA) and obtained a postdoc fellowship in SISSA, Neurobiophysics, Trieste (Italy). His current research within the Centre for laser microscopy that he founded in 2004 is mainly devoted to the cellular mechanism of pathophysiology in models of neurodegenerative diseases and conditions by means of confocal microscopy, time-resolved video microscopy and electrophysiology.
Amyotrophic lateral sclerosis (ALS) is a complex neurological disorder characterized by fatal and selective degeneration of both upper and lower motor neurons, with glial cells playing an important role in the non-cell autonomous disease mechanism. Compromised astrocytic function as well as the involvement of immune-mediated mechanisms have been long recognised. Our previous study demonstrated that the purified IgGs from ALS patients enhance the mobility of acidic vesicles in cultured rodent astrocytes in a Ca2+ dependent manner (inducing IP3-mediated calcium release and entry of extracellular calcium through SOCE channels, with the activation of PI3K upstream of PLC). In the present study we further investigated the acute effect of ALS IgGs and their Fab fragments alone on cytosolic Ca2+ ([Ca2+]i) in rat astrocytes loaded with the calcium-sensitive dye Fluo-4 AM. Time-lapse imaging obtained with 1 s time resolution showed that all purified ALS IgG Fab fragments alone evoked [Ca2+]i changes, with some of them mimicking the effect of the whole IgG. In parallel we also show alterations in calcium homeostasis in primary microglial and hippocampal neuronal cell cultures upon ALS IgG acute treatment. These humoral immune factors induce transient calcium rise and/or an increase in spontaneous network activity of hippocampal neurons in culture. The detailed characterization of calcium responses in different neural cell types will elucidate the subtle intracellular processes and intercellular interactions as promising biomedical diagnostic targets that might help in stratifying patients and lead to the personalized treatments of this complex neurodegenerative disease.
Funding: H2020 MSCA RISE grant 778405 “AUTOIGG”
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