Glutamate receptors in the nucleus tractus solitarius contribute to ventilatory acclimatization to hypoxia in rat

Pamenter, Matthew E.; Carr, J. Austin; Go, Ariel; Fu, Zhenxing; Reid, Scott D.; Powell, Frank L.

doi:10.1113/jphysiol.2013.268706

Cited by 44 publications

(68 citation statements)

References 52 publications

(122 reference statements)

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“…Given that increased breathing due to the acute HVR and VAH in other vertebrates is mediated by excitatory neurotransmitters [6,8], we hypothesized that decreased breathing in the hypoxic naked mole rat might be mediated by increased activity of this key inhibitory neurotransmitter. GABA no longer plays a signalling role in this response after acclimatization to CSH, and that other pathways become dominant.…”

Section: Discussionmentioning

confidence: 99%

“…VAH typically requires a few days to a week to fully manifest [6]. Plasticity changes related to VAH occur mainly at excitatory glutamatergic and dopaminergic synapses, both at the carotid body/carotid sinus nerve and within the CNS components of the ventilatory reflex, and build upon synaptic signalling mechanisms that underlie the acute HVR [8,9,23,24]. Given the otherwise ubiquitous occurrence of VAH in experimental models, it is a remarkable finding of our study that naked mole rats do not exhibit VAH or any apparent plasticity in their ventilatory responses following 8-10 days of CSH.…”

Section: Discussionmentioning

confidence: 99%

“…VAH is ubiquitous in all adult vertebrates studied to date and persists for days to weeks after the removal of the hypoxic stimulus, indicating the occurrence of plasticity within the ventilatory control circuits [7]. In adult mammals, the acute HVR and VAH are primarily mediated by the activation and subsequent remodelling of glutamatergic synapses, which upregulate the gain of excitatory signalling in ventilatory control circuits, resulting in increased breathing in hypoxia [8,9]. The occurrence of VAH has not been explored in naked mole rats but the ventilatory decrease observed during acute hypoxic exposure is partially mediated by an upregulation of inhibitory signalling, with early evidence implicating adenosine as a key regulator of this response [5].…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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“…Microinjection of an AMPA receptor agonist in the nucleus tractus solitaries increased ventilation by 50% under sustained hypoxia, while an AMPA receptor antagonist abolished this effect. Expression of phosphorylated AMPA receptor protein subunits increased in nucleus of the solitary tract of chronic sustained hypoxia rats (Pamenter et al, 2014). However, the mechanisms and modulation of postsynaptic AMPA receptor trafficking during hypoxia are unclear.…”

Section: Introductionmentioning

confidence: 99%

Protein tyrosine kinase regulates α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor trafficking induced by acute hypoxia in cultured brainstem neurons

Wang

Yu²,

2016

Genet. Mol. Res.

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ABSTRACT. This study was performed to investigate the modulation effect of protein tyrosine kinase on postsynaptic a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor trafficking induced by acute hypoxia in cultured brainstem neurons. The cultured neurons were exposed to 1% O 2 and the expression of AMPA receptor subunit GluR2 on the cell surface was significantly increased, while total GluR2 was not markedly changed. Furthermore, the hypoxia- induced increase in GluR2 expression on the cell surface was partially blocked by the protein tyrosine kinase membrane-permeable inhibitor genistein. In contrast, both the protein tyrosine kinase agonist nerve growth factor and protein tyrosine phosphatase inhibitor vanadate promoted the hypoxia-induced increase of GluR2 expression on cell surface. Moreover, GluR2 could be phosphorylated by tyrosine under normoxia and hypoxia conditions in vitro on brainstem neurons, and tyrosine phosphorylation of GluR2 was significantly stronger under hypoxia conditions. Our results indicate that acute hypoxia induces the AMPA receptor subunit GluR2 to rapidly migrate to the cell membrane to modify the strength of the synapse. This study indicates that tyrosine phosphorylation of the receptor is an important pathway regulating the rapid migration of GluR2 in the postsynaptic domain induced by hypoxia.

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“…A similar effect is reported in mice with a specific deletion of the HIF-1α gene in the central nervous system (Bavis et al, 2007), while the induction of HIF-1α expression with desferrioxamine (an iron chelator) in rats enhances ventilatory response to hypoxia (Nguyen et al, 2007). The plasticity occurring in the central nervous system in response to sustained hypoxia involves activation of the glutamatergic signaling pathway in the NTS (Pamenter et al, 2014;Reid and Powell, 2005), and a recent study pointed out that HIF coordinates the transcriptional activation of multiple genes encoding glutamate transporters and receptors in response to hypoxia in cancer cells (Hu et al, 2014); therefore, this might be a way by which HIF-1 induces higher ventilation under hypoxia in mice. HIF-1 is also a key element for metabolic control by promoting glycolysis, and by suppressing the activity of the mitochondrial Krebs cycle and ), (ii) relative protein level (a.u.…”

Section: Hif-1α Expression Is Correlated With Respiratory and Metabolmentioning

confidence: 60%

HIF1α and physiological responses to hypoxia are correlated in mice but not in rats

Jochmans-Lemoine

Shahare

Soliz

et al. 2016

Journal of Experimental Biology

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We previously reported that rats and mice that have been raised for more than 30 generations in La Paz, Bolivia (3600 m), display divergent physiological responses to high altitude, including improved respiratory and metabolic control in mice. In the present study, we asked whether these traits would also be present in response to hypoxia at sea level. To answer this question, we exposed rats (Sprague Dawley) and mice (FVB) to normoxia (21% O 2 ) or hypoxia (15 and 12% O 2 ) for 6 h and measured ventilation and metabolic rate (whole-body plethysmography), and expression of the transcription factor HIF-1α (ELISA and mass spectrometry) and other proteins whose expression are regulated by hypoxia (glucose transporter 1, pyruvate dehydrogenase kinase 1 and angiopoietin 2; mass spectrometry) in the brainstem. In response to hypoxia, compared with rats, mice had higher minute ventilation, lower metabolic rate and higher expression of HIF-1α in the brainstem. In mice, the expression level of HIF-1α was positively correlated with ventilation and negatively correlated with metabolic rate. In rats, the concentration of brainstem cytosolic protein decreased by 38% at 12% O 2 , while expression of the glucose transporter 1 increased. We conclude that mice and rats raised at sea level have divergent physiological and molecular responses to hypoxia, supporting the hypothesis that mice have innate traits that favor adaptation to altitude.

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Glutamate receptors in the nucleus tractus solitarius contribute to ventilatory acclimatization to hypoxia in rat

Cited by 44 publications

References 52 publications

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

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

Protein tyrosine kinase regulates α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor trafficking induced by acute hypoxia in cultured brainstem neurons

HIF1α and physiological responses to hypoxia are correlated in mice but not in rats

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