It has been reported that the clinical symptoms of functional dyspepsia (FD) exacerbate upon stress while the gender-related factors have been incompletely understood. This study aims to investigate the role of sex in chronic heterotypic stress (CHS)-induced autonomic and gastric motor dysfunction. For CHS, the rats were exposed to the combination of different stressors for 7 consecutive days. Subsequently, electrocardiography was recorded in anesthetized rats to evaluate heart rate variability (HRV) for the determination of autonomic outflow and sympathovagal balance. Solid gastric emptying (GE) was measured in control and CHS-loaded male and female rats. The immunoreactivities of catecholaminergic cell marker tyrosine hydroxylase (TH), choline acetyltransferase (ChAT), corticotropin releasing factor (CRF), and estrogen receptor (ER-α/β) were evaluated in medullary and pontine brainstem sections by immunohistochemistry. Compared with the controls, CHS significantly delayed GE in males but not in females. There was no significant sex-related difference in parasympathetic indicator HF under either control or CHS conditions. Sympathetic indicator LF was significantly higher in control females compared to the males. The higher sympathetic output in females was found to be attenuated upon CHS; in contrast, the elevated sympathetic output was detected in CHS-loaded males. No sex- or stress-related effect was observed on ChAT immunoreactivity in the dorsal motor nucleus of N.vagus (DMV). In males, greater number of TH-ir cells was observed in the caudal locus coeruleus (LC), while they were more densely detected in the rostral LC of females. Regardless of sex, CHS elevated immunoreactivity of TH throughout the LC. Under basal conditions, greater number of TH-ir cells was detected in the rostral ventrolateral medulla (RVLM) of females. In contrast, CHS remarkably increased the number of TH-ir cells in the RVLM of males which was found to be decreased in females. There was no sex-related alteration in TH immunoreactivity in the nucleus tractus solitarius (NTS) of control rats, while CHS affected both sexes in a similar manner. Compared with females, CRF immunoreactivity was prominently observed in control males, while both of which were stimulated by CHS. ER-α/β was found to be co-expressed with TH in the NTS and LC which exhibit no alteration related to either sex or stress status. These results indicate a sexual dimorphism in the catecholaminergic and the CRF system in brainstem which might be involved in the CHS-induced autonomic and visceral dysfunction occurred in males.

Color changes and pattern formations can represent strategies of the utmost importance for the survival of individuals or of species. Previous studies have associated capture with the formation of blotches (areas with light color) of coral trout, but the regulatory mechanisms link the two are lacking. Here, we report that capture induced blotches formation within 4-5 seconds. The blotches disappeared after anesthesia dispersed the pigment cells and reappeared after electrical stimulation. Subsequently, combining immunofluorescence, transmission electron microscopy and chemical sympathectomy, we found blotches formation results from activation of catecholaminergic neurons below the pigment layer. Finally, the in vitro incubation and intraperitoneal injection of norepinephrine (NE) induced aggregation of chromatosomes and lightening of body color, respectively, suggesting that NE, a neurotransmitter released by catecholaminergic nerves, mediates blotches formation. Our results demonstrate that acute stress response-induced neuronal activity can drive rapid changes in body color, which enriches our knowledge of physiological adaptations in coral reef fish.

High-calorie diets and chronic stress are major contributors to the development of obesity and metabolic disorders. These two risk factors regulate the activity of the sympathetic nervous system (SNS). The present study showed a key role of the cannabinoid type 1 receptor (CB1) in dopamine β-hydroxylase (dbh)-expressing cells in the regulation of SNS activity. In a diet-induced obesity model, CB1 deletion from these cells protected mice from diet-induced weight gain by increasing sympathetic drive, resulting in reduced adipogenesis in white adipose tissue and enhanced thermogenesis in brown adipose tissue. The deletion of CB1 from catecholaminergic neurons increased the plasma norepinephrine levels, norepinephrine turnover, and sympathetic activity in the visceral fat, which coincided with lowered neuropeptide Y (NPY) levels in the visceral fat of the mutant mice compared with the controls. Furthermore, the mutant mice showed decreased plasma corticosterone levels. Our study provided new insight into the mechanisms underlying the roles of the endocannabinoid system in regulating energy balance, where the CB1 deletion in dbh-positive cells protected from diet-induced weight gain via multiple mechanisms, such as increased SNS activity, reduced NPY activity, and decreased basal hypothalamic-pituitary-adrenal (HPA) axis activity.

This study aimed to determine the effect of age on CVLM C1 neuron glucoregulatory proteins in the feeding pathway. Male Sprague Dawley rats aged 3 months and 24 months old were divided into two subgroups: the treatment group with 2-deoxy-d-glucose (2DG) and the control group. Rat brains were dissected to obtain the CVLM region of the brainstem. Western blot was used to determine protein expression of tyrosine hydroxylase (TH), phosphorylated TH at Serine40 (pSer40TH), AMP-activated protein kinase (AMPK), phosphorylated AMPK (phospho AMPK), and neuropeptide Y Y5 receptors (NPY5R) in CVLM samples. Immunofluorescence was used to determine TH-, AMPK-, and NPY5R-like immunoreactivities among other brain coronal sections. Results obtained denote a decrease in basal TH phosphorylation levels and AMPK proteins and an increase in TH proteins among aged CVLM neurons. Increases in the basal immunoreactivity of TH+, AMPK+, NPY5R+, TH+/AMPK+, and TH+/NPY5R+ were also observed among old rats. Young treatment-group rats saw a decrease in TH phosphorylation and AMPK proteins following 2DG administration, while an increase in AMPK phosphorylation and a decrease in TH proteins were found among the old-treatment-group rats. These findings suggest the participation of CVLM C1 neurons in counter-regulatory responses among young and old rats. Altering protein changes in aged CVLM C1 neurons may attenuate responses to glucoprivation, thus explaining the decline in food intake among the elderly.

A newly discovered physical mechanism involving incoherent electron tunneling in layers of the protein ferritin that are found in catecholaminergic neurons (catecholaminergic neuron electron transport or CNET) is hypothesized to support communication between neurons. Recent tests further confirm that these ferritin layers can also perform a switching function (in addition to providing an electron tunneling mechanism) that could be associated with action selection in those neurons, consistent with earlier predictions based on CNET. While further testing would be needed to confirm the hypothesis that CNET allows groups of neurons to communicate and act as a switch for selecting one of the neurons in the group to assist in reaching action potential, this paper explains how that hypothesized behavior would be consistent with Integrated Information Theory (IIT), one of a number of consciousness theories (CTs). While the sheer number of CTs suggest that any one of them alone is not sufficient to explain consciousness, this paper demonstrates that CNET can provide a physical substrate and action selection mechanism that is consistent with IIT and which can also be applied to other CTs, such as to conform them into a single explanation of consciousness.

Lowered glucose availability, sensed by the hindbrain, has been suggested to enhance gluconeogenesis and food intake as well as suppress reproductive function. In fact, our previous histological and in vitro studies suggest that hindbrain ependymal cells function as a glucose sensor. The present study aimed to clarify the hindbrain glucose sensor-hypothalamic neural pathway activated in response to hindbrain glucoprivation to mediate counterregulatory physiological responses. Administration of 2-deoxy-D-glucose (2DG), an inhibitor of glucose utilization, into the fourth ventricle (4V) of male rats for 0.5 hour induced messenger RNA (mRNA) expression of c-fos, a marker for cellular activation, in ependymal cells in the 4V, but not in the lateral ventricle, the third ventricle or the central canal without a significant change in blood glucose and testosterone levels. Administration of 2DG into the 4V for 1 hour significantly increased blood glucose levels, food intake, and decreased blood testosterone levels. Simultaneously, the expression of c-Fos protein was detected in the 4V ependymal cells; dopamine β-hydroxylase-immunoreactive cells in the C1, C2, and A6 regions; neuropeptide Y (NPY) mRNA-positive cells in the C2; corticotropin-releasing hormone (CRH) mRNA-positive cells in the hypothalamic paraventricular nucleus (PVN); and NPY mRNA-positive cells in the arcuate nucleus (ARC). Taken together, these results suggest that lowered glucose availability, sensed by 4V ependymal cells, activates hindbrain catecholaminergic and/or NPY neurons followed by CRH neurons in the PVN and NPY neurons in the ARC, thereby leading to counterregulatory responses, such as an enhancement of gluconeogenesis, increased food intake, and suppression of sex steroid secretion.

The pontine A5 noradrenergic group contributes to the maturation of the respiratory system before birth in rats. These neurons are connected to the neural network responsible for respiratory rhythmogenesis. In the present study, we investigated the participation of A5 noradrenergic neurons in neonates (P7-8 and P14-15) in the control of ventilation during hypoxia and hypercapnia in in vivo experiments using conjugated saporin anti-dopamine beta-hydroxylase (DβH-SAP) to specifically ablate noradrenergic neurons. Thus, DβH-SAP (420 ng/μL) or saporin (SAP, control) was injected into the A5 region of neonatal male Wistar rats. Hypoxia reduced respiratory variability in control animals; however, A5 lesion prevented this effect in P7-8 rats. Our data suggest that noradrenergic neurons of the A5 region in neonate rats do not participate in the control of ventilation under baseline and hypercapnic conditions, but exert an inhibitory modulation on breathing variability under hypoxic challenge in early life (P7-8).

Some cardiovascular symptoms in the early stage of Parkinson\'s disease (PD) were related to degeneration of the rostral ventrolateral medulla (RVLM) catecholaminergic neurons. To date, little is known about the effects of hydrogen water on early stage of PD. Here, protective actions of hydrogen-saturated saline (HS) on rotenone-induced PD rats, as well as its underlying mechanisms were investigated. HS was used to treat PD rats at three general stages; early, medium and late, which were represented by rotenone induced rats for 0, 7 and 14 days. HS treatment significantly alleviated the cardiovascular and motor symptoms in rotenone-induced PD rats, improved the survival number of RVLM catecholaminergic neurons and nigral dopamine neurons only in early and medium stages of PD rats. Decreased levels of reactive oxygen species (ROS) and alpha-synuclein (α-Syn), transformation of microtubule associated protein 1 light chain 3 (LC3)-I/II and degradation of sequestosome 1 (p62) were detected, as well as increased expression level of autophagy related protein 5 (ATG5) and B-cell lymphoma-2 interacting protein 1 (Beclin-1) in the RVLM and substantia nigra (SN) after HS treatment in early and medium stages of PD rats. In addition, phosphorylation levels of phosphatidylinositol-3-kinase (PI3K), protein kinase B (Akt) and mammalian rapamycin target protein (mTOR) decreased after HS treatment in early and medium stages of PD rats. The results suggested that HS treatment exerted beneficial effects in early and medium stages before motor impairments emerged but not in the late stage of rotenone-induced PD rats. It exerted neuroprotection with RVLM catecholaminergic neurons and nigral dopamine neurons, mediated in part by decreasing levels of ROS and α-Syn through increasing autophagy machinery which were partly via inhibiting PI3K-Akt-mTOR pathway.

High salt intake is able to evoke neuroendocrine and autonomic responses that include vasopressin release and sympathoexcitation resulting in increasing in the arterial blood pressure (BP). The C1 neurons are a specific population of catecholaminergic neurons located in the RVLM region and they control BP under homeostatic imbalance. Thus, here we hypothesized that the ablation of C1 neurons mitigate the high blood pressure induced by high-salt intake. To test this hypothesis, we injected anti-DβH-SAP saporin at the RVLM and monitored the BP in unanesthetized animals exposed to high salt intake of 2% NaCl solution for 7 days. The injection of anti-DβH-SAP into the RVLM depleted 80% of tyrosine hydroxylase-positive neurons (TH+ neurons) in the C1, 38% in the A5, and no significant reduction in the A1 region, when compared to control group (saline as vehicle). High salt intake elicited a significant increase in BP in the control group, while in the anti-DβH-SAP group the depletion of TH+ neurons prevents the salt-induced hypertension. Moreover, the low frequency component of systolic BP and pulse interval were increased by high-salt intake in control animals but not in anti-DβH-SAP group, which indirectly suggests that the increase in the BP is mediated by increase in sympathetic activity. In conclusion, our data show that hypertension induced by high-salt intake is dependent on C1 neurons.

A fundamental question of physiology is how gut-brain signaling stimulates appetite. While many studies have emphasized the importance of vagal afferents to the brain in inducing satiation, little is known about whether and how the vagal-mediated gut-brain pathway senses orexigenic signals and stimulates feeding. Here, we identified a previously uncharacterized population of fasting-activated catecholaminergic neurons in the nucleus of the solitary tract (NTS). After characterizing the anatomical complexity among NTS catecholaminergic neurons, we surprisingly found that activation of NTS epinephrine (ENTS) neurons co-expressing neuropeptide Y (NPY) stimulated feeding, whereas activation of NTS norepinephrine (NENTS) neurons suppressed feeding. Monosynaptic tracing/activation experiments then showed that these NTS neurons receive direct vagal afferents from nodose neurons. Moreover, activation of the vagal→NPY/ENTS neural circuit stimulated feeding. Our study reveals an orexigenic role of the vagal→NTS pathway in controlling feeding, thereby providing important insights about how gut-brain signaling regulates feeding behavior.