Mice with nucleus tractus solitarius injury induced by chronic restraint stress present impaired ability to raise blood glucose and glucagon levels when blood glucose levels plummet.

Chronic restraint stress (CRS) induces insulin-resistant hyperglycemia by inducing injury to the brain neurons in the nucleus tractus solitarius (NTS). However, the CRS mice did not suffer from hypoglycemia. In this study, mice of both CRS and NTS mechanical injury models were induced to investigate whether impaired glucose metabolism has changed upon the extension of the survival time after modeling. Body weight, food and water intake, fasting blood glucose, glucose tolerance, and glucose metabolism related to blood hormone levels were monitored for 12 weeks following the induction of injury. The mice were also administered with insulin intraperitoneally, and the blood glucose and glucagon levels were measured and compared to those in the control mice administered with saline. The results showed that the body weights of CRS-hyperglycemic mice were significantly higher than those in the control group, while the body weights of NTS mechanically injured mice were significantly lower than those in the control group. The food and water intake of both CRS-hyperglycemic and NTS mechanically injured mice were significantly more than those in the control groups. Although the levels of fasting blood glucose and resting serum hormone in the injured mice have returned to normal levels, the utilization of glucose and hypoglycemic counterregulation (the response that raises the blood glucose levels) was impaired in either CRS-hyperglycemic or NTS mechanically injured mice. The blood glucagon levels following insulin administration showed abnormal increase. These findings suggest that the CRS-induced NTS injury resulted not only in early insulin-resistant hyperglycemia but also impaired the ability to raise blood glucose and glucagon levels when blood glucose levels plummet in the later stage.

Supportive effect of interferential current stimulation on susceptibility of swallowing in guinea pigs.

Sensory-motor control of the pharyngeal swallow requires sensory afferent inputs from the pharynx and larynx evoked by introducing bolus into the pharynx. Patients with reduced sensitivity of the pharynx and larynx are likely to have a swallowing impairment, such as pre-swallow aspiration due to delayed swallow triggering. Interferential current stimulation applied to the neck is thought to improve the swallowing function of dysphagic patients, although the mechanism underlying the facilitatory effect of such stimulation remains unknown. In the present study, we examined the changes in the elicitability of swallowing due to the stimulation and the responses of the swallowing-related neurons in the nucleus tractus solitarius and in the area adjacent to the stimulation in decerebrate and paralyzed guinea pigs. The swallowing delay time was shortened by the stimulation, whereas the facilitatory effect of eliciting swallowing was attenuated by kainic acid injection into the nucleus tractus solitarius. Approximately half of the swallowing-related neurons responded to the stimulation. These data suggest that the interferential current stimulation applied to the neck could enhance the sensory afferent pathway of the pharynx and larynx, subserving excitatory inputs to the neurons of the swallowing pattern generator, thereby facilitating the swallowing reflex.

Changes in sodium appetite evoked by lesions of the commissural nucleus of the tractus solitarius

Ablation of the area postrema/caudal nucleus of the tractus solitarius (NTS) complex increases sodium intake, but the effect of selective lesions of the caudal NTS is not known. We measured depletion-induced sodium intake in rats with electrolytic lesions of the commissural NTS that spared the area postrema. One day after the lesion, rats were depleted of sodium with furosemide (10 mg/kg body weight, sc) and then had access to water and a sodium-deficient diet for 24 h when 1.8 percent NaCl was offered. Water and saline intakes were measured for 2 h. Saline intake was higher in lesioned than in sham-lesioned rats (mean ± SEM: 20 ± 2 vs 11 ± 3 mL/2 h, P < 0.05, N = 6-7). Saline intake remained elevated in lesioned rats when the tests were repeated 6 and 14 days after the lesion, and water intake in these two tests was increased as well. Water intake seemed to be secondary to saline intake both in lesioned and in sham-lesioned rats. A second group of rats was offered 10 percent sucrose for 2 h/day before and 2, 7, and 15 days after lesion. Sucrose intake in lesioned rats was higher than in sham-lesioned rats only 7 days after lesioning. A possible explanation for the increased saline intake in rats with commissural NTS lesions could be a reduced gastrointestinal feedback inhibition. The commissural NTS is probably part of a pathway for inhibitory control of sodium intake that also involves the area postrema and the parabrachial nucleus.

Changes in sodium appetite evoked by lesions of the commissural nucleus of the tractus solitarius.

Ablation of the area postrema/caudal nucleus of the tractus solitarius (NTS) complex increases sodium intake, but the effect of selective lesions of the caudal NTS is not known. We measured depletion-induced sodium intake in rats with electrolytic lesions of the commissural NTS that spared the area postrema. One day after the lesion, rats were depleted of sodium with furosemide (10 mg/kg body weight, sc) and then had access to water and a sodium-deficient diet for 24 h when 1.8% NaCl was offered. Water and saline intakes were measured for 2 h. Saline intake was higher in lesioned than in sham-lesioned rats (mean +/- SEM: 20 +/- 2 vs 11 +/- 3 mL/2 h, P < 0.05, N = 6-7). Saline intake remained elevated in lesioned rats when the tests were repeated 6 and 14 days after the lesion, and water intake in these two tests was increased as well. Water intake seemed to be secondary to saline intake both in lesioned and in sham-lesioned rats. A second group of rats was offered 10% sucrose for 2 h/day before and 2, 7, and 15 days after lesion. Sucrose intake in lesioned rats was higher than in sham-lesioned rats only 7 days after lesioning. A possible explanation for the increased saline intake in rats with commissural NTS lesions could be a reduced gastrointestinal feedback inhibition. The commissural NTS is probably part of a pathway for inhibitory control of sodium intake that also involves the area postrema and the parabrachial nucleus.

Lesions of the commissural subnucleus of the nucleus of the solitary tract increase isoproterenol-induced water intake.

The nucleus of the solitary tract (NTS) is the primary site of the cardiovascular afferent information about arterial blood pressure and volume. The NTS projects to areas in the central nervous system involved in cardiovascular regulation and hydroelectrolyte balance, such as the anteroventral third ventricle region and the lateral parabrachial nucleus. The aim of the present study was to investigate the effects of electrolytic lesion of the commissural NTS on water and 0.3 M NaCl intake and the cardiovascular responses to subcutaneous injection of isoproterenol. Male Holtzman rats weighing 280 to 320 g were submitted to sham lesion or electrolytic lesion of the commissural NTS (N = 6-15/group). The sham-lesioned rats had the electrode placed along the same coordinates, except that no current was passed. Water intake induced by subcutaneous isoproterenol (30 microg/kg body weight) significantly increased in chronic (15 days) commissural NTS-lesioned rats (to 2.4 +/- 0.2 vs sham: 1.9 +/- 0.2 mL 100 g body weight-1 60 min-1). Isoproterenol did not induce any sodium intake in sham or in commissural NTS-lesioned rats. The isoproterenol-induced hypotension (sham: -27 +/- 4 vs commissural NTS-lesioned rats: -22 +/- 4 mmHg/20 min) and tachycardia (sham: 168 +/- 10 vs commissural NTS: 144 +/- 24 bpm/20 min) were not different between groups. The present results suggest that the commissural NTS is part of an inhibitory neural pathway involved in the control of water intake induced by subcutaneous isoproterenol, and that the overdrinking observed in lesioned rats is not the result of a cardiovascular imbalance in these animals.

Lesions of the commissural subnucleus of the nucleus of the solitary tract increase isoproterenol-induced water intake

The nucleus of the solitary tract (NTS) is the primary site of the cardiovascular afferent information about arterial blood pressure and volume. The NTS projects to areas in the central nervous system involved in cardiovascular regulation and hydroelectrolyte balance, such as the anteroventral third ventricle region and the lateral parabrachial nucleus. The aim of the present study was to investigate the effects of electrolytic lesion of the commissural NTS on water and 0.3 M NaCl intake and the cardiovascular responses to subcutaneous injection of isoproterenol. Male Holtzman rats weighing 280 to 320 g were submitted to sham lesion or electrolytic lesion of the commissural NTS (N = 6-15/group). The sham-lesioned rats had the electrode placed along the same coordinates, except that no current was passed. Water intake induced by subcutaneous isoproterenol (30 µg/kg body weight) significantly increased in chronic (15 days) commissural NTS-lesioned rats (to 2.4 ± 0.2 vs sham: 1.9 ± 0.2 mL 100 g body weight-1 60 min-1). Isoproterenol did not induce any sodium intake in sham or in commissural NTS-lesioned rats. The isoproterenol-induced hypotension (sham: -27 ± 4 vs commissural NTS-lesioned rats: -22 ± 4 mmHg/20 min) and tachycardia (sham: 168 ± 10 vs commissural NTS: 144 ± 24 bpm/20 min) were not different between groups. The present results suggest that the commissural NTS is part of an inhibitory neural pathway involved in the control of water intake induced by subcutaneous isoproterenol, and that the overdrinking observed in lesioned rats is not the result of a cardiovascular imbalance in these animals.

Receptor changes in the nucleus tractus solitarii of the rat after exercise training.

PURPOSE: The aim of the present study was to evaluate neurotransmitter receptor changes in the nucleus tractus solitarii (NTS) of the rat after exercise training. METHODS: Twelve Wistar Kyoto rats were used. Six rats were submitted to a progressive training program in which they ran on a treadmill 5 d x wk(-1) for 13 wk (trained). The other rats were kept as controls (sedentary). After this period, the rats were killed and the brains processed for quantitative receptor autoradiography. Coronal brain sections were obtained using a cryostat and were incubated with a specific buffer solution containing [(3)H]vasopressin or (3)Hp-aminoclonidine. RESULTS: In the NTS of the trained rats, a decrease in the values of binding parameters (IC(50) and K(D)) of vasopressin receptors was observed, indicating an increase in the affinity of vasopressin receptors. On the other hand, a decreased affinity was observed for alpha(2)-adrenoceptors in the NTS of the trained rats in comparison with the sedentary animals. CONCLUSION: Exercise training leads to changes in vasopressin and alpha(2)-adrenoceptors, which may explain several physiological alterations occurring during physical activity.

The anorectic effect of a chronic peripheral infusion of amylin is abolished in area postrema/nucleus of the solitary tract (AP/NTS) lesioned rats.

OBJECTIVE: Neurons in the area postrema/nucleus of the solitary tract (AP/NTS) region mediate amylin's anorectic effect elicited by a single intraperitoneal (i.p.) injection of a low dose (5 microg/kg). Here, we tested if a sustained elevation in amylin levels which was achieved by chronic amylin infusion reduces food intake by acting in the AP/NTS region or, possibly, at other brain sites. Further, we tested the role of the AP/NTS region in mediating the anorectic effects of high doses of amylin and its receptor agonist salmon calcitonin (sCT) after an acute single injection. DESIGN: Amylin (2 microg/kg/h) was chronically infused i.p. by osmotic minipumps in AP/NTS-lesioned (AP-X) or sham-lesioned (SHAM) rats. For the acute experiments, amylin or sCT was injected i.p. at doses of 0.5 (only sCT), 5 or 50 microg/kg. Food intake was measured by a computerized system. Body weight was assessed by manually weighing the rats. RESULTS: Amylin significantly reduced cumulative food intake for about 7 days in SHAM but not in AP-X rats. Amylin's effect in SHAM rats was mainly due to a reduction of the size of nocturnal meals (eg average meal size during the first four dark phases; SHAM, NaCl 4.1+/-0.6 vs amylin 2.6+/-0.4 g; n=6, P<0.05; AP-X, 2.6+/-0.3 vs 3.7+/-0.3) while light phase food intake was unaffected. Body weight gain over the whole 14 day infusion period was reduced by amylin in SHAM (NaCl 61+/-6 vs amylin 46+/-4 g; P<0.05) but not in AP-X rats (54+/-4 vs 62+/-4). After single injection, the anorectic effect of high doses of amylin and sCT (50 microg/kg) was attenuated, but not abolished, in AP-X rats. CONCLUSION: We conclude that, under our experimental conditions, neurons in the AP/NTS region are necessary for chronically elevated peripheral amylin to reduce food intake in rats. High doses of amylin, however, may be able to overrun these receptors and reduce feeding by acting at other brain sites.

Symmetrical necrosis of the solitary tract nuclei as a contributory cause of death.

A 64-year-old man died in spite of surgery 4 days after attempting suicide. He first tried to hang himself with a rope and when the hanging did not succeed, he cut his throat with a knife. The autopsy showed four sutured cervical wounds with laryngeal wounds but without associated important vascular injury. The neuropathological study revealed two watershed-type haemorrhagic infarcts, involving the left occipital lobe and the left cerebellum. It also showed a symmetrical necrosis of solitary tract nuclei in the medullary tegmentum. Such a lesion is likely to result from sudden acute transient circulatory failure and might have played a role in the secondary autonomous cardiac and respiratory dysfunctions following a non-lethal trauma.

Lesion of the area postrema/nucleus of the solitary tract (AP/NTS) attenuates the anorectic effects of amylin and calcitonin gene-related peptide (CGRP) in rats.

The area postrema/nucleus of the solitary tract (AP/NTS) region plays an important role in the control of food intake since it receives peripheral satiety signals via splanchnic and vagal afferents. Due to the lack of the blood brain barrier in this region, blood borne signals can directly be monitored in the AP/NTS. Furthermore, receptors for anorectic peptides such as amylin or calcitonin gene-related peptide (CGRP) have been found in the AP/NTS. It was therefore the aim of the present study to investigate the role of the AP/NTS region in mediating the anorectic effects of these peptides. Thermal ablation of the AP/NTS resulted in a significant reduction of the anorectic effects of IP injected amylin (5 microg/kg) and CGRP (5 microg/kg) in food deprived rats. The anorectic actions of CCK and BBS were also reduced by the AP/NTS lesion which agrees with previous studies. We conclude that the AP/NTS region is an important brain site for mediating the anorectic effects of amylin and CGRP. It remains to be clarified whether this effect is due to amylin and CGRP action on receptors within the AP/NTS region or peripheral receptors on afferent nerves projecting to the AP/NTS.