Have you ever had a stressful time in your life and then caught a cold? Have you ever wondered why you feel sad and depressed when you are sick? It turns out that it was not all in your head.

Recent research suggests that when our brain senses a threat in the environment (physical, psychological, or social) it sends signals – through a network of peripheral nerves – that mobilizes our immune system to protect us from injury. While this is essential for survival, this excessive effect on the immune system can lead to or aggravate a variety of illnesses including depression, cardiovascular disease, diabetes, and dermatitis among many others. Our recent research has begun to understand the bidirectional connections between the brain and immune system that mediate these effects.

The interactions between the nervous and immune systems are representative of the brain’s mutual connections with all the other organs in the body. The food we eat also effects the gut microbiome which affects both the immune and nervous systems. This Brain and Body Research Center is one of the first research centers in the nation to focus solely on how the brain and body interact.

Research

Stress-related illnesses such as major depressive disorder (MDD) or anxiety disorders are a leading cause of disability worldwide. Both are highly prevalent in patients with cardiovascular disease, irritable bowel disease (IBD), dermatitis, and diabetes, and can aggravate symptoms. In some cases, the conditions are associated with an increased risk of morbidity and mortality. Our world class research teams have found that stress associated with MDD or anxiety is the trigger that often initiates or worsens disease prognosis.

Our current research includes:

• Led by Scott Russo, PhD, and Miriam Merad, MD, PhD, a major research question being tested is how interleukins and other peripheral inflammatory molecules interact with the brain and vice versa to control disease. New research suggests that inflammatory molecules diffuse more readily into the brain following prolonged periods of stress in animal models. Brain imaging investigations propose that MDD patients may suffer from similar damage to blood vessels in the brain.
• Led by Filip Swirski, PhD, research on how chronic stress mobilizes the immune system and increases the production of monocytes, which produces inflammatory molecules called interleukins that circulate throughout the bloodstream. This can contribute to chronic pathology such as atherosclerosis, the leading cause of heart attacks and stroke. Therapeutic strategies to reduce inflammation is currently being tested for their antidepressant properties.
• Led by James Murrough, MD, PhD, a groundbreaking research on human depression is currently being conducted at Mount Sinai. The research shows great potential for novel immune modulatory drugs to treat major depressive disorder. If successful, it would result in the development of one of the first biologically distinct classes of antidepressant therapeutics in decades.
• Led by Filip Swirski, PhD, and Scott Russo, PhD, another research interest aims to understand how specific brain regions – acting through control of peripheral nerves—modulate immune cell function, which in turn results in damaged blood vessels contributing to increased risk for heart disease and depression. The goal is to obtain a detailed mechanistic understanding of this process at the molecular level. In collaboration with the Mount Sinai Drug Discovery Institute.
• Led by Jessica Ables, MD, PhD, another goal of our research is to understand brain and body interactions diabetes. Currently, we use animal models of diabetes to identify the ways in which long-term exposure to hyperglycemia can lead to increased susceptibility to stress and to addiction--or depression--or anxiety-like syndromes. Our goal is to eventually translate these findings to human patients.
• Led by Ivan De Araujo, PhD, we are investigating how signals originating within the body influence our decisions and actions. We study the neural networks that link body sensors to skeletomuscular effectors (“body-brain cybernetics”). Specifically, we make use of modern neurobiological tools to unveil the large-scale networks linking body parts to molecularly identified neurons in the brain. Methodologically, we use the vertebrate feeding system, including predatory hunting, to model body-brain communication. With clear behavioral readouts, feeding and prey capture are ideally suited for studying how body sensors generate motor actions.
• Led by Abha Rajbhandari, PhD, we seek to understand how the brain and body interact during exposure to traumatic stress. Trauma-related disorders like post-traumatic stress disorder (PTSD) involves dysregulation of cardiac and lung function. Our studies show that the brain sends a network of nerves through peripheral tissues and is directly involved in regulating cardiorespiratory function in response to traumatic stress. This type of bottom-up mechanistic approach will aide in the development of novel and targeted therapeutics based on targeting brain body interactions for the treatment of stress-related conditions.
• Led by Mone Zaidi, MD, PhD and Ki Gooses, PhD, this study explores how the thyroid-stimulating hormone receptor (TSHR) regulates physiological processes in the multiple peripheral systems, including the thyroid gland, bone, and gonads. However, our recent work highlights largely undiscovered roles for TSHR in the brain. Using RNAscope and immunofluorescence microscopy, we observed a high density of TSHRs in multiple sites of the mouse brain, including the bed nucleus of stria terminalis and substantia innominata, two regions important for anxiety. The density of TSHR in these brain regions was greater in female mice than male mice. Our work in mice suggests that THSR receptor activity potentiates anxiety, and that maternal THSR activity is important for setting anxiety-like behavior in offspring.  We also observed extremely high densities of TSHR in specialized glial cells called tanycytes. Tanycytes induce rapid structural remodeling of the blood-brain barrier near the metabolic hypothalamus under metabolic challenges such as hunger.  We are investigating the role of TSHR in stress-induced changes in blood-brain barrier permeability.