Medical Research

Huntington Medical Research Institutes

Michael Harrington, Linda Petzold, Brian Stoltz
Pasadena, CA
$1,000,000
December 2019

An interdisciplinary team of investigators at the Huntington Medical Research Institutes, the University of California, Santa Barbara, and the California Institute of Technology proposes a new fundamental biological mechanism in which varying sodium levels in cerebrospinal fluid (CSF) or brain tissue alter local neuronal firing rates, resulting in fluctuation of brain performance.  Their initial studies of migraine pathophysiology revealed that CSF sodium regulation is a key factor in migraine: CSF sodium levels are higher near specific cranial nerves at the time that their excitability increases.  Moreover, based on animal and cell culture studies, the team predicts that fluctuating sodium levels are responsible for fluctuating brain performance in health and disease.  For example, altered sodium in the frontotemporal cortex may change executive and memory functions, while sodium fluctuations in the limbic system, amygdala, and prefrontal cortex may alter mood or cause anxiety or panic attacks.  To test their hypothesis, the investigators will measure sodium and ATPase activity in well-characterized individuals using multinuclear magnetic resonance imaging and will identify symptoms that match the changing biochemistry.  Furthermore, the team will develop new compounds to modulate the sodium/potassium ATPase at different sites to improve neurological functions.  Lastly, they will generate a physics-based model of the data to further our understanding of when, where and how specific episodic neurological functions arise.  Thus, modeling will establish the key rate-limiting steps in a complex brain network to predict failure of brain homeostasis.  Successful completion of this project will ascertain a new paradigm for health or brain pathology, whereby fluctuating neurological functions arise from fluctuating sodium levels.

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