Proteogenomics Reveals Orthologous Alternatively Spliced Proteoforms in the Same Human and Mouse Brain Regions with Differential Abundance in an Alzheimer's Disease Mouse Model.

Alternative splicing (AS) may increase the number of proteoforms produced by a gene. Alzheimer's disease (AD) is a neurodegenerative disease with well-characterized AS proteoforms. In this study, we used a proteogenomics strategy to build a customized protein sequence database and identify orthologous AS proteoforms between humans and mice on publicly available shotgun proteomics (MS/MS) data of the corpus callosum (CC) and olfactory bulb (OB).

Central Ang II (Angiotensin II)-Mediated Sympathoexcitation: Role for HIF-1α (Hypoxia-Inducible Factor-1α) Facilitated Glutamatergic Tone in the Paraventricular Nucleus of the Hypothalamus.

Central infusion of Ang II (angiotensin II) has been associated with increased sympathetic outflow resulting in neurogenic hypertension. In the present study, we appraised whether the chronic increase in central Ang II activates the paraventricular nucleus of the hypothalamus (PVN) resulting in elevated sympathetic tone and altered baro- and chemoreflexes. Further, we evaluated the contribution of HIF-1α (hypoxia-inducible factor-1α), a transcription factor involved in enhancing the expression of N-methyl-D-aspartate receptors and thus glutamatergic-mediated sympathetic tone from the PVN.

Intravenous doxapram administration as a potential model of panic attacks in rats.

Panic disorder can be categorized into the nonrespiratory or the respiratory subtypes, the latter comprising dyspnea, shortness of breath, chest pain, feelings of suffocation, and paresthesias. Doxapram is an analeptic capable of inducing panic attacks with respiratory symptoms in individuals diagnosed with the disorder; however, its neuroanatomical targets and its effects on experimental animals remain uncharacterized. One of the brain regions proposed to trigger panic attacks is the midbrain periaqueductal gray (PAG).

Central angiotensin II-Protein inhibitor of neuronal nitric oxide synthase (PIN) axis contribute to neurogenic hypertension.

Activation of renin-angiotensin- system, nitric oxide (NO•) bioavailability and subsequent sympathoexcitation plays a pivotal role in the pathogenesis of many cardiovascular diseases, including hypertension. Previously we have shown increased protein expression of PIN (a protein inhibitor of nNOS: neuronal nitric oxide synthase, known to dissociate nNOS dimers into monomers) with concomitantly reduced levels of catalytically active dimers of nNOS in the PVN of rats with heart failure. To elucidate the molecular mechanism by which Angiotensin II (Ang II) increases PIN expression, we used Sprague-Dawley rats (250-300 g) subjected to intracerebroventricular infusion of Ang II (20 ng/min, 0.

Effects of alprazolam and cannabinoid-related compounds in an animal model of panic attack.

Selective stimulation of carotid chemoreceptors by intravenous infusion of low doses of potassium cyanide (KCN) produces short-lasting escape responses that have been proposed as a model of panic attack. In turn, preclinical studies suggest that facilitation of the endocannabinoid system attenuate panic-like responses. Here, we compared the effects of cannabinoid-related compounds to those of alprazolam, a clinically effective panicolytic, on the duration of the escape reaction induced by intravenous infusion of KCN (80μg) in rats.

Changes in cardiovascular responses to chemoreflex activation of rats recovered from protein restriction are not related to AT receptors.

What is the central question of this study? In this study, we sought to investigate whether cardiovascular responses to peripheral chemoreflex activation of rats recovered from protein restriction are related to activation of AT receptors. What is the main finding and its importance? This study highlights the fact that angiotensinergic mechanisms activated by AT receptors do not support increased responses to peripheral chemoreflex activation by KCN in rats recovered from protein restriction. Also, we found that protein restriction led to increased resting ventilation in adult rats, even after recovery.

Excitatory amino acid receptors in the dorsomedial hypothalamic area contribute to the chemoreflex tachypneic response.

This study evaluated the effect of blockade of the excitatory amino acid (EAA) receptors in the dorsomedial hypothalamic (DMH) area on the ventilatory and cardiovascular responses of the chemoreflex activation in conscious rats. Bilateral microinjection of kynurenic acid (2.7 nmol, n = 6) into the DMH area reduced the tachypneic (+ 264 ± 13 versus + 204 ± 14 cpm, P < 0.

Exercise training starting at weaning age preserves cardiac pacemaker function in adulthood of diet-induced obese rats.

Peripheral sympathetic overdrive in young obese subjects contributes to further aggravation of insulin resistance, diabetes, and hypertension, thus inducing worsening clinical conditions in adulthood. Exercise training has been considered a strategy to repair obesity autonomic dysfunction, thereby reducing the cardiometabolic risk. Therefore, the aim of this study was to assess the effect of early exercise training, starting immediately after weaning, on cardiac autonomic control in diet-induced obese rats.

Physical exercise performance in temperate and warm environments is decreased by an impaired arterial baroreflex.

The present study aimed to investigate whether running performance in different environments is dependent on intact arterial baroreceptor reflexes. We also assessed the exercise-induced cardiovascular and thermoregulatory responses in animals lacking arterial baroafferent signals. To accomplish these goals, male Wistar rats were subjected to sinoaortic denervation (SAD) or sham surgery (SHAM) and had a catheter implanted into the ascending aorta to record arterial pressure and a telemetry sensor implanted in the abdominal cavity to record core temperature.

Sinoaortic denervation prevents enhanced heat loss induced by central cholinergic stimulation during physical exercise.

The present study investigated whether the effects of central cholinergic stimulation on thermoregulation during exercise are modulated by arterial baroreceptors. Wistar rats were submitted to sinoaortic denervation (SAD) or sham denervation (SHAM) and then fitted with a chronic guide cannula into the lateral cerebral ventricle. After 2 weeks, a catheter was implanted into the ascending aorta, and a temperature sensor was implanted into the peritoneal cavity.

Excitatory amino acid receptors in the dorsomedial hypothalamus are involved in the cardiovascular and behavioural chemoreflex responses.

The present study investigated the role of the dorsomedial hypothalamus (DMH) on cardiovascular and behavioural responses of chemoreflex activation in conscious rats. The arterial chemoreflex was activated by potassium cyanide (KCN, 40 μg, i.v.

Effect of L-NAME microinjected into the nucleus tractus solitarius on jejunal glucose and electrolyte absorption in anesthetized rats.

The aim of the present study was to investigate the effects of N(G)-nitro-L-arginine-methyl-ester (L-NAME) microinjected into the rostral nucleus tractus solitarius (NTS) on jejunal glucose, sodium and potassium absorption. Male Wistar rats (210-250 g, n=6-12) were anesthetized and submitted to midline laparotomy to expose and isolate 20 cm of jejunal loop and perform a subdiaphragmatic truncal vagotomy or sympathectomy. Either 0.

Altered cardiovascular reflexes responses in conscious Angiotensin-(1-7) receptor Mas-knockout mice.

This study evaluated the physiological importance of Angiotensin-(1-7) receptor Mas on reflex control of circulation. Experiments were performed in male Mas-knockout (Mas-KO) and Wild Type (WT) conscious mice (12-20 wk of age). Baroreceptor reflex was evaluated by the bradycardic response induced by phenylephrine (0.

The enhanced hyperglycemic response to hemorrhage hypotension in obese rats is related to an impaired baroreflex.

The aim of the present study was to assess the metabolic adjustments in adult rats with autonomic imbalance induced by hypercaloric diet. Male Wistar rats (4 weeks of age) were fed a chow diet (CD, n = 12) or hypercaloric diet (HD, n = 13) for 19 weeks. Body weight and dietary intake were measured every week and the basal metabolic rate was assessed.

Malnutrition enhances cardiovascular responses to chemoreflex activation in awake rats.

Several studies in the literature suggest that low-protein intake is associated with increases in sympathetic efferent activity and cardiovascular disease. Among the possible mechanisms, changes in the neurotransmission of cardiovascular reflexes have been implicated. Therefore, the present study comprised the evaluation of chemoreflex responsiveness in rats subjected to a low-protein diet during the 35 days after weaning.

Hyperglycemic response to hemorrhage is modulated by baroreceptors unloading but not by peripheral chemoreceptors activation.

The aim of this study was to assess the relative participation of carotid baro- and chemoreceptors on plasma glucose and lactate level in response to hemorrhagic hypotension. We also evaluated the effects of selective activation of carotid chemoreceptors. One week before the experiments, male Wistar rats (250-300 g) were submitted to bilateral total carotid denervation (BCD-group), or to bilateral ligature of the carotid body artery (ChD-group).

Effects of vasoactive intestinal polypeptide microinjected into the nucleus tractus solitarius on jejunal electrolytes absorption in rats.

It has been shown that vasoactive intestinal polypeptide (VIP) injected into the nucleus tractus solitarius inhibits alanine absorption across the jejunum. The aim of the present study was to investigate the effects of VIP injection into the nucleus tractus solitarius on jejunal absorption of electrolytes in the rat. Fifty-three Wistar rats were submitted to midline laparotomy to expose and isolate 20 cm of jejunal loop and to perform a subdiaphragmatic troncular vagotomy.

The hypothalamic paraventricular nucleus and carotid receptors modulate hyperglycemia induced by hemorrhage.

The aim of this study was to assess the role of cholinergic transmission in the paraventricular nucleus of the hypothalamus (PVN) and carotid body receptors in mediating a rise in plasma glucose levels in response to hemorrhagic hypotension in rats. Methylatropine (1x10(-9) mol) or 0.15 M NaCl (0.

Effects of vasoactive intestinal polypeptide microinjected into the nucleus tractus solitarius on jejunal glucose absorption in rats.

It has been shown that vasoactive intestinal polypeptide (VIP) injected into the nucleus tractus solitarius and into the dorsal motor nucleus of the vagus inhibits alanine absorption across the jejunum. The aim of the present study was to investigate the effects of VIP injection into the nucleus tractus solitarius on jejunal absorption of glucose in the rat. Forty Wistar rats were submitted to midline laparotomy to expose and isolate 20 cm of jejunal loop and to perform a subdiaphragmatic troncular vagotomy.

Cardiovascular responses to substance P in the nucleus tractus solitarii: microinjection study in conscious rats.

The cardiovascular effects of substance P (SP) microinjections in the nucleus tractus solitarii (NTS) were evaluated in conscious rats. We chose this model because it is an effective way to access some of the cardiovascular effects of neurotransmitters in the NTS without the inconvenience of blunting pathways with anesthetic agents or removing forebrain projections by decerebration. The cardiovascular responses to SP injections were also evaluated after chronic nodose ganglionectomy.

Characterization of a new selective antagonist for angiotensin-(1-7), D-pro7-angiotensin-(1-7).

Angiotensin-(1-7) [Ang-(1-7)] has biological actions that can often be distinguished from those of angiotensin II (Ang II). Recent studies indicate that the effects of Ang-(1-7) are mediated by specific receptor(s). We now report the partial characterization of a new antagonist selective for Ang-(1-7), D-Pro7-Ang-(1-7).

Involvement of the parabrachial nucleus in the pressor response to chemoreflex activation in awake rats.

Activation of the chemoreflex with potassium cyanide (KCN, 40 microg/rat, i.v.) in awake rats produces pressor and bradycardic responses as well as a tachypneic response.