Autism and "Astro"logy

9th May 2024

Timing : 11:30 am EST

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Important insights into the pathophysiology of fragile X syndrome (FXS), a common monogenic cause of autism spectrum disorder, have emerged from analyses of rodent models. These findings, however, have been less effective in developing therapeutic interventions, thereby highlighting the need for model systems of human origin. Moreover, many studies have focused on neurons, and the role of glia remains largely unexplored in FXS. Here, we used human pluripotent stem cells to examine the potential role of astrocytes in physiological abnormalities in FXS neurons. FXS cortical neurons, co-cultured with FXS astrocytes, fired spontaneous bursts of action potentials that are more frequent, but shorter in duration, compared to control neurons co-cultured with control astrocytes. However, bursts fired by FXS neurons, co-cultured with control astrocytes, are indistinguishable from control neurons. Conversely, control neurons exhibit aberrant firing in the presence of FXS astrocytes. Thus, the genotype of astrocytes determines the physiological phenotype of neurons. Strikingly, astrocytic conditioned medium by itself, from either control or FXS astrocytes is capable of eliciting the same spontaneous burst firing patterns that would be observed if astrocytes were physically present in co-cultures. Further analysis of a mechanistic basis of this effect revealed that the astroglial-derived protein, S100b, restores normal firing by reversing the suppression of a persistent sodium current in FXS neurons. Together, these results identify an important cell non-autonomous contribution of astrocytes in correcting aberrant electrical activity in human FXS neurons, thereby suggesting a framework for exploring new therapeutic strategies aimed at neuron-glia interactions.



Snow
Professor Sumantra Chattarji
Director
Center for High Impact Neuroscience and Translational Applications (CHINTA)
Kolkata, India
Visiting Professor
Simons Initiative for the Developing Brain
University of Edinburgh, UK

Sumantra Chattarji received his Master’s degree in Physics from the Indian Institute of Technology, Kanpur. He then went on to do a Ph.D. in Neuroscience at the Johns Hopkins University and Salk Institute. After post-doctoral research at Yale University and MIT, he started his own laboratory at the National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India in 1999. His research has shown that prolonged stress leaves its mark by enhancing both the physiological and structural basis of synaptic connectivity in the amygdala, thereby triggering the emotional symptoms observed in stress-related psychiatric disorders. His lab also studies synaptic defects and their reversal in Fragile X Syndrome, the leading identified cause of autism. Prof. Chattarji was recently awarded the Global Champion Award by the Fragile X Research Foundation, USA. He is a Fellow of the Indian Academy of Sciences, International Union of Physiological Sciences, and EMBO. He also serves on the Council of the Society for Neuroscience.