Astrocyte regulation of circadian behavior
Italian Institute of Technology (Genova, Italy)
The human brain contains more than 100 billion cells, the majority being non-excitable glial cells, remarkably coordinated by an intrinsic clock to determine alertness waxes and wanes in highly predictable manner over the course of a 24-hour day. Genetic or environmental insults affecting this circadian clock accelerate aging and dramatically impacts sleep, cognitive functions and energy balance. Neurons in the suprachiasmatic nuclei of the hypothalamus are described as master pacemaker cells for these biological rhythms. However, it remains unclear how this clock signaling is orchestrated within so many brain cells that lead to the cycle-to-cycle precision of circadian rhythmicity.
Astrocytes, the most abundant cell type in the brain, cooperate with presynaptic and postsynaptic neuronal elements to regulate communication events and behavioral processes. While being directly involved in neuronal signaling, the implication of astrocytes in the timekeeping system had not being deeply investigated so far. In my talk, I will present my research on the contributions of astrocyte clock to the circadian timekeeping system. I found that deletion of the core clock gene BMAL1 in astrocytes desynchronizes the neuronal clocks, leading to altered circadian locomotor behavior and severely impaired cognition in mammals. Moreover, ablation of astrocytic BMAL1 is sufficient to shorten life span and alter energy balance and glucose homeostasis, phenocopying constitutive Bmal1 knockout mice. By demonstrating that astrocyte rhythmicity is required for the correct organization of oscillators at cellular, tissue and organism level, one of the most important finding arising from my studies is that the long-standing assumption that SCN neurons are the units in Chronobiology ought to be reconsidered.
I have a strong interest in the mechanism(s) by which astrocytes regulate brain function in physiological and pathological conditions, specifically those associated to altered circadian rhythms such as metabolic and aged-related neuropathologies. My research approach is to combine molecular and cellular neurobiology, glial technologies, genetics/epigenetics, behavioral neuroscience and chronobiological techniques.
Host: Jose Luis Zugaza