Central sympathetic network for thermoregulatory responses to psychological stress

Abstract

In mammals, many types of psychological stressors elicit a variety of sympathoexcitatory responses paralleling the classic fight-or-flight response to a threat to survival, including increased body temperature via brown adipose tissue thermogenesis and cutaneous vasoconstriction, and increased skeletal muscle blood flow via tachycardia and visceral vasoconstriction. Although these responses are usually supportive for stress coping, aberrant sympathetic responses to stress can lead to clinical issues in psychosomatic medicine. Sympathetic stress responses are mediated mostly by sympathetic premotor drives from the rostral medullary raphe region (rMR) and partly by those from the rostral ventrolateral medulla (RVLM). Hypothalamomedullary descending pathways from the dorsomedial hypothalamus (DMH) to the rMR and RVLM mediate important, stress-driven sympathoexcitatory transmission to the premotor neurons to drive the thermal and cardiovascular responses. The DMH also likely sends an excitatory input to the paraventricular hypothalamic nucleus to stimulate stress hormone release. Neurons in the DMH receive a stress-related excitation from the dorsal peduncular cortex and dorsal tenia tecta (DP/DTT) in the ventromedial prefrontal cortex. By connecting the corticolimbic emotion circuit to the central sympathetic and somatic motor systems, the DP/DTT → DMH pathway plays as the primary mediator of the psychosomatic signaling that drives a variety of sympathetic and behavioral stress responses. These brain regions together with other stress-related regions constitute a central neural network for physiological stress responses. This network model is relevant to understanding the central mechanisms by which stress and emotions affect autonomic regulations of homeostasis and to developing new therapeutic strategies for various stress-related disorders. muscles and the nervous system, which boosts physical and neural performance (Bishop, 2003). Simultaneously, stress-induced elevations of blood pressure and heart rate (i.e., cardiovascular responses) increase the supply of oxygen and energy sources (sugars and fatty acids) to skeletal muscles, thermogenic organs and the central nervous system. Another major sympathetic response to psychological stress is cutaneous Abbreviations: BAT, brown adipose tissue; CRH, corticotropin-releasing hormone; dDMH, dorsal part of the dorsomedial hypothalamus; dlPAG, dorsolateral subnucleus of the periaqueductal grey;

Hyperthermia as a trigger for Takotsubo syndrome in a rat model

“…Increases in body temperature from 38 to 41°C in rats have been shown to increase sympathetic nerve discharge rate ( 11 , 25 ), and may be supporting the hyper-catecholaminergic state present in the rat when isoproterenol is administered, particularly given the half-life of isoprenaline is <5 minu and a single dose of isoprenaline has been shown to induce persistent pathological cardiac changes ( 12 ). AMP-activated protein kinase (AMPK) is ubiquitously expressed throughout the body, and has been implicated in the pathophysiology of TTS as endomyocardial tissue biopsies taken during the acute TTS phase show increased PI3K/Akt pathway activity ( 26 ), which can be activated by AMPK ( 27 ).…”

“…It was noticed during initial experiments that body temperature tended to rise after isoprenaline administration. A rise in body temperature is known to be produced by high catecholamine levels (once known as “emotional fever”) ( 11 ), as is a suite of immunoinflammatory changes ( 12 ). In our experiments, the rise in body temperature was controlled by adjusting the external heating support for the anesthetized animal, which remained euthermic throughout.…”

Neural Circuitry for Stress Information of Environmental and Internal Odor Worlds

“…The DP and TTd are located in the medial part of the olfactory peduncle. They project to the dorsomedial hypothalamus (DMH) that targets to sympathetic premotor neurons in the brainstem ( Figure 1 ; Nakamura and Morrison, 2022 ). This observation suggests that the DP and TTd transform the retronasal odor information to sympathetic stress-responses.…”

“…Then, which neural pathway is responsible for the stress responses to retronasal odors? It has been shown that the DP and TTd in the medial OC play a role as a hub in transforming a variety of psychological stress-signals to sympathetic thermogenesis and cardiovascular responses via the pathway through DMH, rostral medullary raphe region (rMR), and rostral ventrolateral medulla (RVLM) ( Figure 1 ; Kataoka et al, 2020 ; Nakamura and Morrison, 2022 ). Because the DP and TTd receive rich inputs from MCs and TCs in the medial map of the OB, we speculate that stress-inducing internal odors activate the DP and TTd and transmit aversive odor signals to the DMH-rMR/RVLM-sympathetic pathway, thus inducing the sympathetic responses.…”

“…The TTd and DP have reciprocal connections with infralimbic cortex (IL), which projects to the autonomic centers in the hypothalamus and brainstem, such as DMH, LH, parabrachial nucleus (PBN), and nucleus of solitary tract (NTS). The ventral part of DMH projects to the paraventricular nucleus of hypothalamus (PVH) and activates the hypothalamo-pituitary-adrenal axis to release stress hormones ( Herman et al, 2016 ; Nakamura and Morrison, 2022 ). The lateral stream (blue arrows) originates from the lateral map of the OB (blue) and sends orthonasal/exteroceptive odor information to the external and lateral parts of the anterior olfactory nucleus (AONe, AONl), lateral part of the olfactory tubercle (OTl), ventral and dorsal parts of the anterior piriform cortex (APCv, APCd), posterior piriform cortex (PPC), nucleus of the lateral olfactory tract (NLOT), anterior, posterolateral, and posteromedial nuclei of the cortical amygdala (aCoA, plCoA, pmCoA), medial amygdala (MeA), amygdalo-piriform transition area (AmPir), and lateral entorhinal area (ENTl).…”