In a study recently published in Cell, Technion scientists explore the brain’s potential to cause diseases on its own. Specifically, they induced inflammation in mice, and then triggered the neurons in the brain that were active during the initial inflammation.
The study was conducted by the research group of Associate Professor Asya Rolls from the Technion Ruth and Bruce Rappaport Faculty of Medicine, led by Tamar Koren, an M.D./Ph.D. student in the lab.
They showed that during colon inflammation, several brain regions exert enhanced neuronal activity, one of which was the insular cortex (insula). The insula is an area in the brain responsible for interoception, that is the sense of the body’s physiological state. This includes hunger, thirst, pain, and heart rate.
The researchers postulated that if report of inflammation in some area of the body is stored somewhere in the brain, this area responsible for interoception would be involved.
Armed with this hypothesis, they induced in mice an inflammation in the colon and using genetic manipulation techniques, “captured” groups of neurons in the insular cortex that showed increased activity during the inflammation.
Once the mice were healthy, the researchers triggered these “captured” neurons artificially. Without any outside stimulus other than this triggering of cells in the brain, inflammation re-emerged, in the exact same area where it was before. “Remembering” the inflammation was enough to reactivate it.
If the brain can generate disease, is it possible that it can also turn it off?
Although this was a basic study in mice, and there are multiple challenges in translating the concept to humans, these discoveries open a new therapeutic avenue for treating chronic inflammatory conditions such as Crohn’s disease, psoriasis, and other autoimmune conditions, by attenuating their memory trace in the brain.
“There are evolutionary advantages to such a connection,” said Prof. Rolls in explaining the strange phenomenon whereby the immune system should be activated by memory alone, without an outside trigger.
“The body needs to respond to infection as quickly as possible before the attacking bacteria or viruses can multiply. If certain activity, for example consuming particular foods, has exposed the body to infection and inflammation once, there is an advantage to gearing up for battle when one is about to engage in the same activity again.
A shorter response time would allow the body to defeat the infection faster and with less effort. The problem of course is when such an effective mechanism goes out of control and can on its own generate the disease.”
The group’s findings have broad implications for understanding the way the human mind and body affect each other, but also more immediate implications for understanding and treating illness with a psychosomatic element, like irritable bowel syndrome, and even autoimmune diseases and allergies.
Losing a spouse can be a very stressful life event that places individuals at risk for mental and physical health problems (1, 2). Particularly in the immediate weeks and months following spousal loss, bereavement is associated with increased risk of multimorbidity and mortality (2–5), including an elevation in inflammation-related health problems (6–10), cardiovascular disease (CVD) (8, 11–14), and some types of cancer (12).
Despite a large body of research in the trauma literature attempting to identify risk factors for adverse health outcomes following spousal bereavement, however, the mechanisms through which mental and physical health problems emerge following interpersonal loss remain poorly understood.
Over the past 30 years, the field of psychoneuroimmunology has helped elucidate how different life stressors affect autonomic nervous system, neuroendocrine, and immune processes that could in turn be relevant for understanding the psychobiology of bereavement (15, 16).
In particular, the past decade has produced a substantial body of knowledge shedding light on how specific types of stressors can trigger increases in inflammation (15, 17–21), which has in turn been linked with the development of numerous disease conditions, including autoimmune disorders, CVD, and some cancers, as well as mortality (12).
Consequently, bereavement-related dysregulation in immune function may be one potential process that underlies the increased risk for morbidity and mortality seen in spousal bereaved individuals (22).
One strategy for better understanding the psychobiology of bereavement involves applying what we know about depression, which is also strongly precipitated by interpersonal loss. One model in particular, the Social Signal Transduction Theory of Depression (20), may be helpful for shedding light on how spousal loss and grief affect neural and immune processes that in turn structure risk for health problems following bereavement.
In brief, this theory suggests that both early and later-life stress can promote neuro-inflammatory sensitivity to subsequently occurring stressors and thus heighten a person’s vulnerability to physical and mental health problems across the lifespan. In the context of bereavement, this would occur if an individual with a history of past life stress exposure lost a terminally-ill spouse in adulthood after a sustained period of caregiving burden, in turn leading to mental and physical health problems that have an inflammatory basis.
Recently, Knowles et al. (23) published an excellent systematic review that focused on the link between bereavement and immune system functioning. The present review also examines links between bereavement and immune functioning but seeks to go beyond prior work by providing an integrated account of psychosocial, neural, immunologic, and genomic processes linking bereavement and health, as well as a description of how cumulative lifetime stress exposure may alter vulnerability to mental and physical health problems following spousal loss.
To accomplish this goal, we conducted a PubMed literature search of all relevant studies published through October 2019 using the following key words: bereavement, mental health, physical health, psychobiology, stress, genetic, epigenetic, neuroendocrine, neuroimmune, inflammation, and immunity. To be considered for this review, articles had to be peer reviewed and written in English (see Supplementary Table 1). The psychometric instruments used in the eligible studies are summarized in Table 1.
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reference link : https://www.frontiersin.org/articles/10.3389/fpsyt.2020.565239/full
Original Research: Closed access.
“Insular cortex neurons encode and retrieve specific immune responses” by Tamar Koren et al. Cell