Krill Prize 2017
Dr. Asya Rolls
Physiological mechanisms of brain-body interactions.
The philosophical ‘mind-body problem’ examines the relationship between the mind, a mental process, and the body, a physical entity. In modern medicine, this dialog between the mental and physical state has multiple manifestations, for example, the emergence of disease following stress, or recovery in response to placebo treatment. Nevertheless, this fundamental aspect of physiology remains largely unexplored. My laboratory approaches this question by examining neuronal networks underlying specific brain-body interactions. We examine how the activity of specific brain regions, or specific neuronal ensembles correlated with defined emotional states, affects the immune system, the body’s main protective mechanism.
Using this approach, we recently uncovered a novel potential mechanism of the placebo response. For the past 50 years, most clinical trials include a placebo group to control for non-specific effects such as statistical errors, disease ontology, as well as patient expectations. This expectation of the patient for clinical improvement plays a key role in the placebo response, but it is not known how such expectation affects recovery. We used pharmacogenetics (DREADDs), a state of the art tool in neuroscience, to activate the reward system (dopaminergic neurons in the ventral tegmental area) and analyzed the effects on the immune system. We found that reward system activation strengthens the immediate, innate anti-bacterial immune response, as well as enhancing the formation of long-term immunological memory. We further showed that these effects were mediated via the sympathetic nervous system. These findings were recently published in Nature Medicine (Ben Shaanan, 2016), accompanied by a News and Views report in Nature Medicine, and were featured in Nature and Nature Neuroscience. We hypothesized that because natural rewards such as feeding and sex increase exposure to pathogens, coupling such rewarding activities with increased immunity can be of evolutionary benefit.
Our follow up study demonstrated that reward system activation can attenuate tumor growth by over 40%. We showed that these effects were mediated by an enhancement in the anti-tumor immune response, due to altered innervation to the bone marrow, the site of immune cell formation. This study proposes a potential mechanistic insight to extensive epidemiological data indicating that the patient’s mood is correlated with cancer progression (Spiegel, Lancet, 1989; Spiegel, Cancer, 2007). We expect that by uncovering the mechanisms underlying such brain-immune communication, we will be able to define means to harness the therapeutic potential embedded in the brain.
Accordingly, follow up projects in the laboratory are designed to dissect the specific effects of the peripheral nervous system on the immune compartment. We developed three strains of transgenic mice, each allowing us to control -through optogenetics- a different component of the peripheral nervous system, sympathetic, parasympathetic and serotonergic. We can now manipulate the innervation to the gut, bone marrow, lymph nodes and thymus using laser light, uncovering novel modes of communication between the nervous and immune systems.
This research direction builds on my multidisciplinary background, which places me in a unique position to investigate brain regulation of immunity. We expect this study to alter our understanding of brain-body interactions, and to set the stage for novel approaches to analyze how the state of the mind impacts physiology.