A unifying theory of brain signaling and its possible role in acquired chronic disease

Acquired chronic disease is a significant, growing problem. Research has sought patient abnormalities that drugs can target, but to date, these have only provided equivocal symptom relief and no cures. However, as individual neuronal signals cannot be measured, the role of the brain in such diseases, has not been properly investigated. Here the authors propose that corticotropin-releasing factor (CRF) and serotonin act together in dedicated circuits, to architect precise, bidirectional signals that regulate normal function (e.g., thermoregulation, movement, memory, glomerular filtration rate). The authors propose further that the natural, circuit-specific upregulation of the CRF receptor type 2 (CRFR2), unidirectionally dysregulates these signals to cause chronic symptoms (e.g., low temperature, impaired movement, memory loss, reduced glomerular filtration rate). If confirmed, this view of chronic symptoms as a dysregulation of normal process via neuronal adaptation, has profound implications. It could explain Parkinson's, Alzheimer's and chronic kidney disease, among others, and, as it may be possible to downregulate CRFR2, could reverse the signs and symptoms of such diseases.