The brain norepinephrine system, stress and cardiovascular vulnerability

Abstract

Chronic exposure to psychosocial stress has adverse effects on cardiovascular health, however the stress-sensitive neurocircuitry involved remains to be elucidated. The anatomical and physiological characteristics of the locus coeruleus (LC)-norepinephrine (NE) system position it to contribute to stress-induced cardiovascular disease. This review focuses on cardiovascular dysfunction produced by social stress and a major theme highlighted is that differences in coping strategy determine individual differences in social stress-induced cardiovascular vulnerability. The establishment of different coping strategies and cardiovascular vulnerability during repeated social stress has recently been shown to parallel a unique plasticity in LC afferent regulation, resulting in either excitatory or inhibitory input to the LC. This contrasting regulation of the LC would translate to differences in cardiovascular regulation and may serve as the basis for individual differences in the cardiopathological consequences of social stress. The advances described suggest new directions for developing treatments and/or strategies for decreasing stress-induced cardiovascular vulnerability.

The spatial and cell-type distribution of SARS-CoV-2 receptor ACE2 in human and mouse brain

“…For the spatial distribution of ACE2 in human brain, we found ACE2 may be relatively high (Z score>1) expressed in many important brain nuclei as follows: (1) brain areas where located the neural cell bodies of different neuromodulators, including dopaminergic nuclei (midbrain reticular formation, VTA and substantia nigra), serotoninergic nuclei (midbrain raphe nuclei) (Pollak Dorocic et al, 2014), histaminergic nuclei (tuberomammillary nucleus, TM) (Hu and Chen, 2017), and norepinephrinergic nuclei (locus ceruleus) (Wood and Valentino, 2017); (2) Brain areas participating in important physiologic functions, including posterior hypothalamic area (involved in the control of the sleep-wake cycle, cardiovascular regulation and the expression of defensive-aggressive behavior)(Katagiri et al, 2013), paraventricular nuclei of thalamus (involved in the control of wakefulness, feeding, appetitive motivation, drug addiction, regulation of stress and negative emotional behavior, and epilepsy)(Chen et al, 2020; Ren et al, 2018), paraventricular nucleus of the hypothalamus (neuroendocrine neurons regarding oxytocin, vasopressin, corticotropin-releasing hormone, thyrotropin-releasing hormone)(Qin et al, 2018), and lateral hypothalamic area (the central regulation of hunger, thirst, rewarding, and autonomic nervous system) (Stuber and Wise, 2016); (3) Other brain areas, including amygdalo-hippocampal transition area (related to fear expression) (Fujisaki et al, 2004), hippocampal CA2 field (related to learning and memory) (Dudek et al, 2016), fastigial nucleus (related to body and eye movements) (Zhang et al, 2016), and piriform cortex (related to the sense of smell and epilepsy) (Cheng et al, 2020). Thus, our results may provide some clues to further study on the brain infection of SARS-CoV-2 in the COVID-19 patients, and suggesting SARS-CoV-2 might be able to result in serious CNS symptoms in COVID-19 patients (if it could infect these important brain areas by binding ACE2).…”

Vagally mediated gastric effects of brain stem α2-adrenoceptor activation in stressed rats

“…In rats, stressful stimuli induce an upregulation of central catecholamine levels in areas such as the locus coeruleus (25,60) and the neurons of the A2 group (41,44). Stress-mediated activation of the locus coeruleus, however, increases colonic motility but does not appear to modulate gastric functions (40,51,55,58).…”

“…Central catecholamines are known to play a prominent role in the stress-related pathophysiology, and robust catecholaminergic responses to stress are mediated via neurons of the A2 and A6 (locus coeruleus) areas, which provide inputs to hypothalamic neurons involved in the HPA axis response (32,41,60,61). In particular, the A2 area, embedded in the caudal brainstem comprising neurons of both NTS and DMV (30,34,59), is located strategically to provide a modulation of the neurocircuits that control vagal sensory-motor reflexes, including vagal motor outputs to the upper GI tract.…”

Psycho-Behavioral Spiral of Disturbances in Prosocial Behavior, Stress Response, and Self-Regulation inSubstance-Related and Addictive Disorders

“…The fight-or-flight response is dependent upon a functioning noradrenergic system [90,91]. On the other hand, tendand-befriend activity is associated with oxytocin and related hormones/neurotransmitters [2].…”