GABA-mediated neurotransmission in the nucleus of the solitary tract alters resting ventilation following exposure to chronic hypoxia in conscious rats

Chung, Sean; Ivy, Gwen O.; Reid, Scott D.

doi:10.1152/ajpregu.00645.2005

Cited by 15 publications

(17 citation statements)

References 36 publications

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“…GABA A receptors in the pons are upregulated during chronic hypoxia (23), but dissociated NTS neurons from chronically hypoxic rats exhibit decreased sensitivity to GABA A receptor blockers (58). Also, inhibiting GABA neurotransmission in the caudal NTS decreases ventilatory drive in chronically hypoxic rats breathing normoxic gas (10). This is opposite the increase in ventilatory drive predicted by our results, if the NK1R lesions destroyed the inhibitory cells with GABA receptors too.…”

Section: R348 Ventilatory Effect Of Nk1r Lesion In the Ntscontrasting

confidence: 81%

Ventilatory effects of substance P-saporin lesions in the nucleus tractus solitarii of chronically hypoxic rats

Wilkinson

Powell

2011

American Journal of Physiology-Regulatory, Integrative and Comp

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Wilkinson KA, Fu Z, Powell FL. Ventilatory effects of substance P-saporin lesions in the nucleus tractus solitarii of chronically hypoxic rats. Am J Physiol Regul Integr Comp Physiol 301: R343-R350, 2011. First published May 18, 2011 doi:10.1152/ajpregu.00375.2010.-During ventilatory acclimatization to hypoxia (VAH), time-dependent increases in ventilation lower PCO2 levels, and this persists on return to normoxia. We hypothesized that plasticity in the caudal nucleus tractus solitarii (NTS) contributes to VAH, as the NTS receives the first synapse from the carotid body chemoreceptor afferents and also contains CO2-sensitive neurons. We lesioned cells in the caudal NTS containing the neurokinin-1 receptor by microinjecting the neurotoxin saporin conjugated to substance P and measured ventilatory responses in awake, unrestrained rats 18 days later. Lesions did not affect hypoxic or hypercapnic ventilatory responses in normoxic control rats, in contrast to published reports for similar lesions in other central chemosensitive areas. Also, lesions did not affect the hypercapnic ventilatory response in chronically hypoxic rats (inspired PO 2 ϭ 90 Torr for 7 days). These results suggest functional differences between central chemoreceptor sites. However, lesions significantly increased ventilation in normoxia or acute hypoxia in chronically hypoxic rats. Hence, chronic hypoxia increases an inhibitory effect of neurokinin-1 receptor neurons in the NTS on ventilatory drive, indicating that these neurons contribute to plasticity during chronic hypoxia, although such plasticity does not explain VAH. chemosensitivity; substance P conjugated saporin; ventilatory acclimatization to hypoxia MULTIPLE AREAS OF THE BRAIN stem have been established as CO 2 sensitive by both stimulation and lesion experiments (3-5, 11, 29, 36, 42-44, 47). The organization and significance of these multiple chemoreceptor sites is a major question in this field, and different sites may play different roles in controlling ventilation (V I) or the cardiovascular system during different states (19,38,41). We hypothesized that CO 2 -sensitive chemoreceptors in the nucleus tractus solitarii (NTS) play a role in ventilatory acclimatization to chronic hypoxia.This hypothesis is based on several published observations. First, chronic hypoxia changes the ventilatory response to CO 2 (60), and the NTS contains CO 2 -sensitive cells (11,14,43). Also, the NTS receives the first synapse from O 2 -sensitive afferents from the carotid bodies (15,21,22,33,59), and this could lead to hypoxic or activity-dependent plasticity that has been demonstrated in the central nervous system with chronic hypoxia (16,49,62). The NTS is, therefore, well suited to integrate the increased hypoxic drive to breathe from the arterial chemoreceptors with the decreased drive to breathe from hypocapnia in chronic hypoxia.To test the role of CO 2 -sensitive chemoreceptors in the NTS to ventilatory acclimatization to hypoxia, we studied the effects of NTS lesions. Large lesions to the NT...

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Section: R348 Ventilatory Effect Of Nk1r Lesion In the Ntscontrasting

confidence: 81%

Ventilatory effects of substance P-saporin lesions in the nucleus tractus solitarii of chronically hypoxic rats

Wilkinson

Powell

2011

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Importantly, a role for g-amino butyric acid (GABA), which is the primary inhibitory neurotransmitter in the adult mammalian central nervous system (CNS), and acts at 25-40% of the synapses within the CNS [10], has yet to be investigated. Relative to glutamate, GABA does not play a major role in the acute HVR or VAH in other small rodents [11,12], however, given the polarity between the HVR of naked mole rats and that of other small rodents (decreased versus increased breathing in acute hypoxia), we hypothesized that GABAergic signalling may be important in regulating the HVR or HMR of naked mole rats to both acute and prolonged hypoxia. Therefore, the aims of this study were to (i) evaluate the occurrence of plasticity in ventilatory and metabolic responses of naked mole rats after 8-10 days of chronic sustained normoxia (CSN: 21% O 2 ) or CSH (8% O 2 ) and (ii) evaluate a role for GABAergic neurotransmission in regulating the acute HVR, VAH and the HMR of naked mole rats.…”

Section: Introductionmentioning

confidence: 95%

Naked mole rats exhibit metabolic but not ventilatory plasticity following chronic sustained hypoxia

et al. 2016

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ResearchCite this article: Chung D, Dzal YA, Seow A, Milsom WK, Pamenter ME. 2016 Naked mole rats exhibit metabolic but not ventilatory plasticity following chronic sustained hypoxia. Naked mole rats are among the most hypoxia-tolerant mammals identified and live in chronic hypoxia throughout their lives. The physiological mechanisms underlying this tolerance, however, are poorly understood. Most vertebrates hyperventilate in acute hypoxia and exhibit an enhanced hyperventilation following acclimatization to chronic sustained hypoxia (CSH). Conversely, naked mole rats do not hyperventilate in acute hypoxia and their response to CSH has not been examined. In this study, we explored mechanisms of plasticity in the control of the hypoxic ventilatory response (HVR) and hypoxic metabolic response (HMR) of freely behaving naked mole rats following 8-10 days of chronic sustained normoxia (CSN) or CSH. Specifically, we investigated the role of the major inhibitory neurotransmitter g-amino butyric acid (GABA) in mediating these responses. Our study yielded three important findings. First, naked mole rats did not exhibit ventilatory plasticity following CSH, which is unique among adult animals studied to date. Second, GABA receptor (GABAR) antagonism altered breathing patterns in CSN and CSH animals and modulated the acute HVR in CSN animals. Third, naked mole rats exhibited GABAR-dependent metabolic plasticity following longterm hypoxia, such that the basal metabolic rate was approximately 25% higher in normoxic CSH animals than CSN animals, and GABAR antagonists modulated this increase.

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“…Group 2 was not given any treatment and assigned as HFD control. Group 3 was given DMSO 1ml kg -1 day -1 , i.p 19 and assigned as vehicle control. Group 4 was given orlistat 30mg kg -1 day -1 , p.o.…”

Section: Methodsmentioning

confidence: 99%

“…Group 4 was given orlistat 30mg kg -1 day -1 , p.o. 19 and assigned as standard control. Group 5 and 6 were given bicuculline 0.6 and 1.25mg kg -1 day -1 , i.p.…”

Section: Methodsmentioning

confidence: 99%

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2017

IJPSR

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Arcuate nucleus GABAergic system plays an important role in the energy balance evidenced by various studies. The present study was designed to investigate the involvement of GABA type A receptor in experimental obesity. In the present study effects of chronic administration of diazepam (0.5 and 1mg/kg/day, i.p) and bicuculline (0.6 and 1.25mg/kg/day, i.p) specific GABA type A receptor agonist and antagonist respectively for 8 weeks along with high fat diet to the obese rats which were pre-treated with high fat diet feeding for 8 weeks on the various parameters of obesity were analysed. Treatment with bicuculline (0.6 and 1.25mg/kg/day, i.p) produced significant dose dependent decrease (p < 0.05) in various parameters of obesity as compared to high fat diet group. Diazepam (0.5 and 1mg/kg/day, i.p) produced dose dependent increase in the feeding behaviour in experimental obese rats, while the other parameters were not significantly altered with chronic administration of diazepam as compared to high fat diet control group. Diazepam a negatively alter the parameters of obesity, while the bicuculline positively modulate the parameters of obesity. The present data demonstrated that high fat diet induced obesity was prevented by GABA type A receptor blocker bicuculline. The diazepam a GABA type A receptor agonist increased the feeding behaviour in rats and promote the fat deposition which in-turn result in obese rats, while this effect was not significantly differ from the alone high fat diet group. These findings give the strong evidence of involvement of GABA type A receptor in obesity.

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GABA-mediated neurotransmission in the nucleus of the solitary tract alters resting ventilation following exposure to chronic hypoxia in conscious rats

Cited by 15 publications

References 36 publications

Ventilatory effects of substance P-saporin lesions in the nucleus tractus solitarii of chronically hypoxic rats

Ventilatory effects of substance P-saporin lesions in the nucleus tractus solitarii of chronically hypoxic rats

Naked mole rats exhibit metabolic but not ventilatory plasticity following chronic sustained hypoxia

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