RESUMEN
AIMS: In rats, stress-induced hyperthermia caused by social interaction depends on brown adipose tissue (BAT) thermogenesis and peripheral vasoconstriction. However, the peripheral mechanisms responsible for regulating the level of hyperthermia during social stress are still unknown. The transient receptor potential vanilloid 1 (TRPV1) subfamily, expressed in sensory and visceral neurons, can serve as a thermoreceptor. Here, we tested the hypothesis that the abdominal TRPV1 is essential in regulating stress-induced hyperthermia during social stress. MAIN METHODS: Male Wistar rats received an intraperitoneal injection of Resiniferatoxin (RTX) - an ultra-potent capsaicin analog, (i.e., to desensitize the TRPV1 channels) or vehicle. Seven days later, we evaluated the effects of abdominal TRPV1 channels desensitization on core body temperature (CBT), brown adipose tissue (BAT) temperature, tail skin temperature, and heart rate (HR) of rats subjected to a social stress protocol. KEY FINDINGS: We found abdominal TRPV1 desensitization increased CBT and BAT temperature but did not change tail skin temperature and HR during rest. However, under social stress, we found that abdominal TRPV1 desensitization heightened the increase in CBT and BAT caused by stress. Also, it abolished the increase in tail skin temperature that occurs during and after social stress. TRPV1 desensitization also delayed the HR recovery after the exposure to the social stress. SIGNIFICANCE: These results show that abdominal TRPV1 channels desensitization heightens stress-induced hyperthermia, causing heat dissipation during and after social stress, enabling optimal thermal control during social encounters.
Asunto(s)
Hipertermia Inducida , Canales Catiónicos TRPV , Animales , Masculino , Ratas , Capsaicina/farmacología , Ratas Sprague-Dawley , Ratas Wistar , Canales Catiónicos TRPV/fisiologíaRESUMEN
Overweight and obesity are a worldwide pandemic affecting billions of people. These conditions have been associated with a chronic low-grade inflammatory state that is recognized as a risk factor for a range of somatic diseases as well as neurodevelopmental disorders, anxiety disorders, trauma- and stressor-related disorders, and affective disorders. We previously reported that the ingestion of a high-fat diet (HFD; 45% fat kcal/g) for nine weeks was capable of inducing obesity in rats in association with increased reactivity to stress and increased anxiety-related defensive behavior. In this study, we conducted a nine-week diet protocol to induce obesity in rats, followed by investigation of anxiety-related defensive behavioral responses using the elevated T-maze (ETM), numbers of FOS-immunoreactive cells after exposure of rats to the avoidance or escape task of the ETM, and neuroinflammatory cytokine expression in hypothalamic and amygdaloid nuclei. In addition, we investigated stress-induced cutaneous thermoregulatory responses during exposure to an open-field (OF). Here we demonstrated that nine weeks of HFD intake induced obesity, in association with increased abdominal fat pad weight, increased anxiety-related defensive behavioral responses, and increased proinflammatory cytokines in hypothalamic and amygdaloid nuclei. In addition, HFD exposure altered avoidance- or escape task-induced FOS-immunoreactivity within brain structures involved in control of neuroendocrine, autonomic, and behavioral responses to aversive stimuli, including the basolateral amygdala (BLA) and dorsomedial (DMH), paraventricular (PVN) and ventromedial (VMH) hypothalamic nuclei. Furthermore, rats exposed to HFD, relative to control diet-fed rats, responded with increased tail skin temperature at baseline and throughout exposure to an open-field apparatus. These data are consistent with the hypothesis that HFD induces neuroinflammation, alters excitability of brain nuclei controlling neuroendocrine, autonomic, and behavioral responses to stressful stimuli, and enhances stress reactivity and anxiety-like defensive behavioral responses.
Asunto(s)
Regulación de la Temperatura Corporal/fisiología , Dieta Alta en Grasa/efectos adversos , Neuroinmunomodulación/fisiología , Amígdala del Cerebelo/metabolismo , Animales , Ansiedad/metabolismo , Trastornos de Ansiedad/metabolismo , Corticosterona , Hipotálamo/metabolismo , Masculino , Obesidad , Proteínas Proto-Oncogénicas c-fos/metabolismo , Ratas , Ratas Wistar , Aumento de PesoRESUMEN
The scorpion envenoming syndrome is an important worldwide public health problem due to its high incidence and potential severity of symptoms. Some studies address the high sensitivity of the central nervous system to this toxin action. It is known that cardiorespiratory manifestations involve the activation of the autonomic nervous system. However, the origin of this modulation remains unclear. Considering the important participation of the dorsomedial hypotalamus (DMH) in the cardiovascular responses during emergencial situations, the aim of this work is to investigate the involvement of the DMH on cardiovascular responses induced by intracerebroventricular (icv) injection of Tityustoxin (TsTX, a α-type toxin extracted from the Tityus serrulatus scorpion venom). Urethane-anaesthetized male Wistar rats (n=30) were treated with PBS, muscimol or ionotropic glutamate receptor antagonists, bilaterally in DMH and later, with an icv injection of TsTX, or treated only with PBS in both regions. TsTX evoked a marked increase in mean arterial pressure and heart rate in all control rats. Interestingly, injection of muscimol, a GABAA receptor agonist, did not change the pressor and tachycardic responses evoked by TsTX. Remarkably, the injection ionotropic glutamate receptors antagonists in DMH abolished the pressor and the tachycardic response evoked by TsTX. Our data suggest that the central circuit recruited by TsTX, whose activation results in an array of physiological and behavioral alterations, depend on the activation of DMH ionotropic glutamate receptors. Moreover, our data provide new insights on the central mechanisms involved in the development of symptoms in the severe scorpion envenomation syndrome.
Asunto(s)
Núcleo Hipotalámico Dorsomedial/efectos de los fármacos , Hipertensión/metabolismo , Receptores Ionotrópicos de Glutamato/metabolismo , Venenos de Escorpión/toxicidad , Taquicardia/metabolismo , Animales , Presión Arterial/efectos de los fármacos , Núcleo Hipotalámico Dorsomedial/metabolismo , Agonistas de Receptores de GABA-A , Hipertensión/inducido químicamente , Inyecciones Intraventriculares , Masculino , Ratas , Ratas Wistar , Receptores de GABA-A/metabolismo , Receptores Ionotrópicos de Glutamato/antagonistas & inhibidores , Venenos de Escorpión/administración & dosificación , Taquicardia/inducido químicamenteRESUMEN
There is ample evidence that both lateral/dorsolateral periaqueductal gray (l/dlPAG) and basolateral amygdala (BLA) are essential for the regulation of the autonomic responses evoked during innate reactions to threatening stimuli. However, it is not well established to what extent the BLA regulates the upstream functional connection from the l/dlPAG. Here we evaluated the role of the BLA and its glutamatergic receptors in the cardiovascular responses induced by l/dlPAG stimulation in rats. We examined the influence of acute inhibition of the BLA, unilaterally, by injecting muscimol on the cardiovascular responses evoked by the injection of N-methyl D-aspartate (NMDA) into the l/dlPAG. We also evaluated the role of BLA ionotropic glutamate receptors in these responses by injecting antagonists of NMDA and AMPA/kainate receptor subtypes into the BLA. Our results show that the microinjection of NMDA in the BLA increased the mean arterial pressure (MAP) and heart rate (HR). Injection of NMDA into the l/dlPAG caused similar increases in these variables, which was prevented by the prior injection of muscimol, a GABAA agonist, into the BLA. Moreover, injection of glutamatergic antagonists (2-amino-5-phosphonopentanoate (AP5) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)) into the BLA reduced the increase in MAP and HR induced by l/dlPAG activation. Finally, the inhibition of the central amygdala neurons failed to reduce the cardiovascular changes induced by l/dlPAG activation. These results indicate that physiological responses elicited by l/dlPAG activation require the neuronal activity in the BLA. This ascending excitatory pathway from the l/dlPAG to the BLA might ensure the expression of the autonomic component of the defense reaction.
Asunto(s)
Amígdala del Cerebelo/fisiología , Presión Arterial/fisiología , Frecuencia Cardíaca/fisiología , Neuronas/fisiología , Sustancia Gris Periacueductal/fisiología , Receptores de Glutamato/metabolismo , 2-Amino-5-fosfonovalerato/farmacología , 6-Ciano 7-nitroquinoxalina 2,3-diona/farmacología , Amígdala del Cerebelo/efectos de los fármacos , Animales , Presión Arterial/efectos de los fármacos , Agonistas de Aminoácidos Excitadores/farmacología , Antagonistas de Aminoácidos Excitadores/farmacología , Agonistas de Receptores de GABA-A/farmacología , Ácido Glutámico/metabolismo , Frecuencia Cardíaca/efectos de los fármacos , Masculino , Microinyecciones , Muscimol/farmacología , N-Metilaspartato/farmacología , Neuronas/efectos de los fármacos , Sustancia Gris Periacueductal/efectos de los fármacos , Ratas Wistar , Receptores de GABA-A/metabolismoRESUMEN
Rats fed a high-fat diet (HFD) present an exaggerated endocrine response to stress conditions, which, like obesity, show a high correlation with cardiovascular diseases. Meanwhile the GABAergic neurotransmission within the dorsomedial hypothalamus (DMH) is involved in the regulation of the physiological responses during emotional stress. Here we evaluated the influence of obesity, induced by a HFD, on the cardiovascular responses induced by air jet stress in rats, and the role of the GABAergic tonus within the DMH in these changes. Our results showed that consumption of a HFD (45% w/w fat) for 9 weeks induced obesity and increases in baseline mean arterial pressure (MAP) and heart rate (HR). Moreover, obesity potentiated stress responsiveness, evidenced by the greater changes in MAP and HR induced by stress in obese rats. The injection of muscimol into the DMH reduced the maximal increases in HR and MAP induced by stress in both groups; however, the reduction in the maximal increases in MAP in the HFD group was less pronounced. Moreover, the injection of muscimol into the DMH of obese rats was less effective in reducing the stress-induced tachycardia, since the HR attained the same levels at the end of the stress paradigm as after the vehicle injection. Injection of bicuculline into DMH induced increases in MAP and HR in both groups. Nevertheless, obesity shortened the tachycardic response to bicuculline injection. These data show that obesity potentiates the cardiovascular response to stress in rats due to an inefficient GABAA-mediated inhibition within the DMH.
Asunto(s)
Presión Arterial/fisiología , Dieta Alta en Grasa/efectos adversos , Frecuencia Cardíaca , Obesidad/fisiopatología , Receptores de GABA-A/metabolismo , Estrés Psicológico/fisiopatología , Ácido gamma-Aminobutírico/metabolismo , Animales , Presión Arterial/efectos de los fármacos , Bicuculina/farmacología , Emociones , Agonistas de Receptores de GABA-A/farmacología , Antagonistas de Receptores de GABA-A/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Masculino , Muscimol/farmacología , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Estimulación Física , Ratas , Ratas Wistar , Estrés Psicológico/complicaciones , Estrés Psicológico/tratamiento farmacológico , Taquicardia/tratamiento farmacológico , Taquicardia/etiología , Taquicardia/fisiopatología , Factores de TiempoRESUMEN
Few studies have investigated whether neuronal function in the amygdaloid complex is necessary for the occurrence of the cardiovascular response to natural (unconditioned) environmental threats. In the present investigation in conscious unrestrained Sprague-Dawley rats we inactivated neuronal function in the amygdaloid complex acutely (bilateral muscimol injections) or chronically (unilateral or bilateral ibotenic acid injections) and measured the effect on sudden falls in tail artery blood flow elicited by non-noxious salient stimuli (sympathetic cutaneous vasomotor alerting responses, SCVARs). After acute bilateral injection of vehicle (200nl Ringer's solution) the SCVAR index was 81 ± 2%, indicating that tail blood flow was reduced by 81% in response to the salient stimuli. After acute bilateral injection of muscimol (1 nmol in 200 nl of Ringer's solution) into the amygdaloid complex the SCVAR index was 49 ± 5%, indicating that tail blood flow was reduced by 49% in response to the salient stimuli (p<0.01 versus vehicle, n=7 rats for vehicle and 6 for muscimol). One week after unilateral ibotenic acid lesions, the SCVAR index was 68 ± 3%, significantly less than 90 ± 1%, the corresponding value after unilateral injection of vehicle (p<0.01, n=6 rats in each group). After bilateral ibotenic acid lesions the SCVAR index was 52 ± 4%, significantly less than 93 ± 1%, the corresponding value after bilateral injection of vehicle (p<0.001, n=6 rats in each group). Ibotenic acid caused extensive neuronal destruction of the whole amygdaloid complex, as well as lateral temporal lobe structures including the piriform cortex. Our results demonstrate that the amygdaloid complex plays an important role in mediating the tail artery vasoconstriction that occurs in rats in response to the animal's perception of a salient stimulus, redirecting blood to areas of the body with more immediate metabolic requirements.
Asunto(s)
Amígdala del Cerebelo/fisiología , Estado de Conciencia/fisiología , Neuronas/fisiología , Cola (estructura animal)/irrigación sanguínea , Cola (estructura animal)/fisiología , Vasoconstricción/fisiología , Amígdala del Cerebelo/efectos de los fármacos , Animales , Estado de Conciencia/efectos de los fármacos , Ácido Iboténico/administración & dosificación , Infusiones Intraventriculares , Masculino , Muscimol/administración & dosificación , Neuronas/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Flujo Sanguíneo Regional/efectos de los fármacos , Flujo Sanguíneo Regional/fisiología , Cola (estructura animal)/efectos de los fármacos , Vasoconstricción/efectos de los fármacosRESUMEN
Psychological stress elicits increases in sympathetic activity accompanied by a marked cardiovascular response. Revealing the relevant central mechanisms involved in this phenomenon could contribute significantly to our understanding of the pathogenesis of stress-related cardiovascular diseases, and the key to this understanding is the identification of the nuclei, pathways and neurotransmitters involved in the organization of the cardiovascular response to stress. The present review will focus specifically on the dorsomedial hypothalamus, a brain region now known to play a primary role in the synaptic integration underlying the cardiovascular response to emotional stress.
Asunto(s)
Sistema Cardiovascular/fisiopatología , Núcleo Hipotalámico Dorsomedial/fisiopatología , Estrés Psicológico/fisiopatología , Sistema Nervioso Simpático/fisiopatología , Animales , Neuronas/fisiología , RatasRESUMEN
Brown adipose tissue (BAT), body and brain temperatures, as well as behavioral activity, arterial pressure and heart rate, increase episodically during the waking (dark) phase of the circadian cycle in rats. Phase-linking of combinations of these ultradian (<24 h) events has previously been noted, but no synthesis of their overall interrelationships has emerged. We hypothesized that they are coordinated by brain central command, and that BAT thermogenesis, itself controlled by the brain, contributes to increases in brain and body temperature. We used chronically implanted instruments to measure combinations of bat, brain and body temperatures, behavioral activity, tail artery blood flow, and arterial pressure and heart rate, in conscious freely moving Sprague-Dawley rats during the 12-h dark active period. Ambient temperature was kept constant for any particular 24-h day, varying between 22 and 27 degrees C on different days. Increases in BAT temperature (> or = 0.5 degrees C) occurred in an irregular episodic manner every 94+/-43 min (mean+/-SD). Varying the temperature over a wider range (18-30 degrees C) on different days did not change the periodicity, and neither body nor brain temperature fell before BAT temperature episodic increases. These increases are thus unlikely to reflect thermoregulatory homeostasis. Episodic BAT thermogenesis still occurred in food-deprived rats. Behavioral activity, arterial pressure (18+/-5 mmHg every 98+/-49 min) and heart rate (86+/-31 beats/min) increased approximately 3 min before each increase in BAT temperature. Increases in BAT temperature (1.1+/-0.4 degrees C) were larger than corresponding increases in brain (0.8+/-0.4 degrees C) and body (0.6+/-0.3 degrees C) temperature and the BAT episodes commenced 2-3 min before body and brain episodes, suggesting that BAT thermogenesis warms body and brain. Hippocampal 5-8 Hz theta rhythm, indicating active engagement with the environment, increased before the behavioral and autonomic events, suggesting coordination by brain central command as part of the 1-2 h ultradian basic rest-activity cycle (BRAC) proposed by Kleitman.
Asunto(s)
Tejido Adiposo Pardo/fisiología , Encéfalo/fisiología , Ritmo Circadiano/fisiología , Termogénesis/fisiología , Animales , Conducta Animal/fisiología , Presión Sanguínea/fisiología , Temperatura Corporal , Regulación de la Temperatura Corporal/fisiología , Femenino , Privación de Alimentos/fisiología , Frecuencia Cardíaca/fisiología , Hipocampo/fisiología , Masculino , Periodicidad , Ratas , Ratas Sprague-Dawley , Flujo Sanguíneo Regional/fisiología , Descanso/fisiología , Ritmo TetaRESUMEN
To determine the prevalence of intestinal parasitism in the Tembé settlements, parasitological examination was performed in December 1996 in the entire population (93 Indians). Hookworms were found in 29.0%, A. lumbricoides in 34.4%, E. histolytica in 12.9%, and G. lamblia in 4.3% of the individuals. The Turé-Mariquita settlement had the highest prevalence of hookworms and A. lumbricoides, while Acará-Mirim had the highest prevalence of E. histolytica and G. lamblia. No differences in mean age were found between Indians with parasites and Indians without parasites. The association between intestinal parasites and sex was nonsignificant, except for the prevalence of hookworms, which was very high in males (38.6%) compared to females (20.4%). The study showed a high prevalence of some intestinal parasites in the Tembé settlements, indicating that primary and secondary health measures should taken immediately for the prevention of intestinal parasitoses.