Corticotropin releasing hormone and imaging, rethinking the stress axis

Abstract

The stress system provides integration of both neurochemical and somatic physiologic functions within organisms as an adaptive mechanism to changing environmental conditions throughout evolution. In mammals and primates the complexity and sophistication of these systems has surpassed other species in triaging neurochemical and physiologic signaling to maximize chances of survival. Corticotropin releasing hormone (CRH) and its related peptides and receptors have been identified over the last three decades and are fundamental molecular initiators of the stress response. They are crucial in the top down regulatory cascade over a myriad of neurochemical, neuroendocrine and sympathetic nervous system events. From neuroscience, we’ve seen that stress activation impacts behavior, endocrine and somatic physiology and influences neurochemical events that one can capture in real time with current imaging technologies. To delineate these effects one can demonstrate how the CRH neuronal networks infiltrate critical cognitive, emotive and autonomic regions of the central nervous system (CNS) with somatic effects. Abundant preclinical and clinical studies show inter-regulatory actions of CRH with multiple neurotransmitters/peptides. Stress, both acute and chronic has epigenetic effects which magnify genetic susceptibilities to alter neurochemistry; stress system activation can add critical variables in design and interpretation of basic and clinical neuroscience and related research. This review will attempt to provide an overview of the spectrum of known functions and speculative actions of CRH and stress responses in light of imaging technology and its interpretation. Metabolic and neuroreceptor positron emission/single photon tomography (PET/SPECT), functional magnetic resonance imaging (fMRI), anatomic MRI, diffusion tensor imaging (DTI), proton magnetic resonance spectroscopy (pMRS) are technologies that can delineate basic mechanisms of neurophysiology and pharmacology. Stress modulates the myriad of neurochemical and networks within and controlled through the central and peripheral nervous system and the effects of stress activation on imaging will be highlighted.

Chronic psychosocial stress during pregnancy affects maternal behavior and neuroendocrine function and modulates hypothalamic CRH and nuclear steroid receptor expression

“…It remains to be assessed if in our model CeA CRH expression may be modulating behavioral changes, via its effect on HPA axis function or its neuromodulatory capacity on target neurons 80 . Our findings of decreased CRHR1 could be interpreted as being adaptive to protect from neurotoxic or metabolic challenges related to excessive CRH signaling 81 . In humans, increased levels of CRH have been reported in PPD 76 and been suggested as a possible diagnostic criterion for the disease 82 .…”

CRF-like receptor SEB-3 in sex-common interneurons potentiates stress handling and reproductive drive in C. elegans

“…In humans, addiction, anxiety, depression and other psychological disorders are linked to dysregulation of CRF signalling in the extended amygdala. Consistent with this, studies using mouse genetic knockout mutants suggest that activated CRF1 receptor promotes stress reactions (flight or freeze responses), whereas the CRF2 receptor dampens or manages rodent stress 45 46 47 48 . CRF1 receptor antagonists that can reduce stress-induced HPA axis activation in rodents have been identified; however, their efficacy in human clinical trials have been inconsistent 49 50 51 .…”

Prediction of Molecular Mechanisms for LianXia NingXin Formula: A Network Pharmacology Study

“…The stimulation of chronic stress will lead to constant HPA axis excitation. It will cause disorders of the endocrine system, imbalanced physiological functions, and mental disorders ( Contoreggi, 2015 ). The increase of GC synthesis is a key factor in HPA axis mechanism; the constant increase of GC promotes immune system activity and inflammatory response, injures vascular endothelial cells, and accelerates arteriolosclerosis (AS) ( Deuchar et al, 2011 ; Cho et al, 2015 ).…”