KAUST Research Workshop on Innovative Technologies to Study Brain Energy Metabolism
Universität Heidelberg, Germany
Professor Agarwal is interested in combining mouse genetics, molecular biology and opto-electrophysiology techniques to understand the neural cells interaction in the mammalian brain. He is particularly interested in astrocytes and oligodendrocytes. He would likes to understand how intricate neuron-glia interactions are essential for generating complex neuropsychological processes such as memory and thoughts, and disruption of such cell-cell communications leads to various neurological and psychiatric disorders.
The brain constitutes only 2% of the total body mass but consumes ~25% of total glucose utilized by our body. According to the recent studies, astrocytes, a ubiquitous glial cells population, uptake ~50% of the total glucose and this number further increases upon enhanced brain activity. Thus, astrocytes play a significant role in brain energy production, storage, and consumption. Astrocytes provide metabolic support to the neighboring neurons and are responsible for performing essential homeostatic processes ranging from restoring ion gradients to maintaining the blood-brain barrier. Since astrocytes and neurons are structurally intertwined, and energy supply and demand are tightly coupled in the brain, astrocytes are well positioned to regulate such "neurometabolic coupling". But the mechanism by which astrocytes and neurons communicate to precisely balance the supply and demand of energy metabolites is not well understood. Astrocytes express a variety of receptors for neurotransmitters, which induce transient increases in intracellular calcium ion (Ca2+). Ca2+ changes in astrocytes can enhance glucose mobilization and influence the activity of surrounding neurons. However, the mechanisms that control Ca2+ signaling in astrocyte and their relationship to receptor-mediated Ca2+ transients are undefined. In my laboratory, we combine molecular, optophysiological and advanced in vivo microscopic techniques, novel mouse genetics tools and computational methodologies to study Ca2+ signals in astrocytes. We investigate the mechanisms that generate Ca2+ signals in astrocytes, and decipher the downstream cellular processes regulated by these signals. To understand the metabolic cross-talk between astrocytes and neurons in vivo, we study the cellular mechanism by which neurons modulate metabolic state of astrocytes. These studies will help us to understand the intimate neuron-glia interactions, which are required for an efficient functioning of neural circuits, and to identify the disturbances in these interactions that can contribute to various metabolic and neurological disorders.