Neurochemical development of brain stem nuclei involved in the control of respiration

Wong‐Riley, Margaret T.T.; Liu, Qiuli

doi:10.1016/j.resp.2005.01.011

Cited by 110 publications

(128 citation statements)

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“…Significantly, at or around postnatal day (P) 12, the expression of excitatory neurotransmitter glutamate and its N-methyl-D-aspartate receptors dropped precipitously, whereas the expression of inhibitory neurotransmitter ␥-aminobutyric acid (GABA), GABA B receptors, and glycine receptors rose sharply (27,30,61). Concomitantly, there was a sudden fall in cytochrome oxidase activity (27,28,61), a sensitive indicator of metabolic capacity and neuronal activity (60). We hypothesized that at and around P12 is a sensitive period in the postnatal development of the rat's respiratory control network, when a transient dominance of inhibitory over excitatory neurotransmission renders the animals less capable of overcoming exogenous respiratory stressors.…”

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confidence: 99%

Postnatal development of metabolic rate during normoxia and acute hypoxia in rats: implication for a sensitive period

Liu¹,

Fehring²,

Lowry³

et al. 2009

Journal of Applied Physiology

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Liu Q, Fehring C, Lowry TF, Wong-Riley MTT. Postnatal development of metabolic rate during normoxia and acute hypoxia in rats: implication for a sensitive period. J Appl Physiol 106: 1212-1222, 2009. First published December 31, 2008 doi:10.1152/japplphysiol.90949.2008.-Previously, we reported that the hypoxic ventilatory response (HVR) in rats was weakest at postnatal day (P) P13, concomitant with neurochemical changes in respiratory nuclei. A major determinant of minute ventilation (V E) is reportedly the metabolic rate [O2 consumption (V O2) and CO2 production (V CO2)]. The present study aimed at testing our hypothesis that daily metabolic rates changed in parallel with ventilation during development and that a weak HVR at P13 was attributable mainly to an inadequate metabolic rate in hypoxia. Ventilation and metabolic rates were monitored daily in P0 -P21 rats. We found that 1) ventilation and metabolic rates were not always correlated, and V E/V O2 and V E/V CO2 ratios were not constant during development; 2) metabolic rate and V E/V O2 and V E/V CO2 ratios at P0 -P1 were significantly different from the remaining first postnatal week in normoxia and hypoxia; 3) at P13, metabolic rates and V E/V O2 and V E/V CO2 ratios abruptly increased in normoxia and were compromised in acute hypoxia, unlike more stable trends during the remaining second and third postnatal weeks; and 4) the respiratory quotient (V CO2/V O2) was quite stable in normoxia and fluctuated slightly in hypoxia from P0 to P21. Thus our data revealed heretofore unsuspected metabolic adjustments at P0 -P1 and P13. At P0 -P1, ventilation and metabolic rates were uncorrelated, whereas at P13, they were closely correlated under normoxia and hypoxia. The findings further strengthened the existence of a critical period of respiratory development around P13, when multiple physiological and neurochemical adjustments occur simultaneously. carbon dioxide production; critical period; oxygen consumption; respiratory quotient; ventilation PREVIOUSLY, WE CONDUCTED DETAILED, day-to-day studies of various brain stem respiratory nuclei of the rat and found that neurotransmitters and receptors underwent distinct developmental changes. Significantly, at or around postnatal day (P) 12, the expression of excitatory neurotransmitter glutamate and its N-methyl-D-aspartate receptors dropped precipitously, whereas the expression of inhibitory neurotransmitter ␥-aminobutyric acid (GABA), GABA B receptors, and glycine receptors rose sharply (27,30, 61). Concomitantly, there was a sudden fall in cytochrome oxidase activity (27,28, 61), a sensitive indicator of metabolic capacity and neuronal activity (60). We hypothesized that at and around P12 is a sensitive period in the postnatal development of the rat's respiratory control network, when a transient dominance of inhibitory over excitatory neurotransmission renders the animals less capable of overcoming exogenous respiratory stressors. Our subsequent ventilatory studies revealed striking changes in normoxic ventilation ...

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confidence: 99%

Postnatal development of metabolic rate during normoxia and acute hypoxia in rats: implication for a sensitive period

Liu¹,

Fehring²,

Lowry³

et al. 2009

Journal of Applied Physiology

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“…Such a window of vulnerability has been reported in P12 rats with an absence of increasing V E /V O2 , due to a decrease in tidal volume and a comparatively weak metabolic response to hypoxia; a response that was different from that in the rest of the first 3 postnatal weeks (Liu et al, 2006). In addition, a reduction in excitatory and an increase in inhibitory neurotransmitters (Wong-Riley and Liu, 2005) as well as a significant decline in tryptophan hydroxylase and serotonin transporter immunoreactivity (Liu and Wong-Riley, 2010b;Liu and Wong-Riley, 2010a) further suggests that normal development can contribute to a narrow window of vulnerability in rats at this age (P12), though lack of proper controls limits the interpretation of these developmental studies. Developmentally, the P12 dunnart (eye opening at P49; weaning at P70) is markedly more immature when compared with the P12 rat (eye opening at P14.5; weaning at P21), with lungs that are yet to commence alveolarisation (Simpson et al, 2011).…”

Section: The Journal Of Experimental Biology 215 (24)mentioning

confidence: 69%

The ventilatory response to hypoxia and hypercapnia is absent in the neonatal fat-tailed dunnart

Simpson

Fong

Cummings

et al. 2012

Journal of Experimental Biology

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SUMMARYAt birth, the newborn fat-tailed dunnart relies on cutaneous gas exchange to meet metabolic demands, with continuous lung ventilation emerging several days later. We hypothesised that the delayed expression of lung ventilation (V E ) in these animals is in part due to a low responsiveness of the respiratory control system to blood gas perturbations. To address this hypothesis, we assessed the ventilatory and metabolic response to hypoxia (10% O 2 ) and hypercapnia (5% CO 2 ) using closed-system respirometry from birth to 23days postpartum (P). Neonatal fat-tailed dunnarts displayed no significant hypoxic or hypercapnic ventilatory responses at any age. Regardless, significant hyperventilation through a suppression of metabolic rate (V O2 ) was observed at birth in response to hypercapnia and in response to hypoxia at all ages, except P12. Therefore, reliance on cutaneous gas exchange during early life may be partially attributed to reduced chemosensitivity or a lack of central integration of chemosensitive afferent information. This may be in part due to the relative immaturity of this species at birth, compared with other mammals.

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“…Details of antibodies and concentrations of antigen for preabsorption testing are summarized in Table 2. Differences in immunoreactivity were carefully compared [26]. Double immunofluorescence: Cryostat sections were also used for double immunofluorescence for Kir channel subunits with 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) and glial fibrillary acidic protein (GFAP) in order to identify the Kir immunoreactive glial cells in the oblongata.…”

Section: Methodsmentioning

confidence: 99%

Immunohistochemical Distribution of Inwardly Rectifying K+ Channels in the Medulla Oblongata of the Rat

et al. 2008

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ABSTRACT. The inwardly rectifying K + channels, Kir1.1, Kir2.3 and Kir4.1-Kir5.1, are the candidate chemosensory molecules for CO 2 / H + . We determined the mRNA expression and immunohistochemical localization of these channels in the medulla oblongata of the rat. RT-PCR analysis revealed mRNAs of Kir1.1, Kir2.3, Kir4.1 and Kir5.1 were detected in the medulla. The immunoreactivities for Kir1.1, Kir2.3, Kir4.1, and Kir5.1 were observed in the medulla, and immunolabeling pattern was varied by the subunit. Immunoreactivities for Kir1.1 and Kir2.3 were observed in the nerve cell bodies and glial cells both in the chemosensory areas [nucleus tractus solitarius (NTS), nucleus raphe obscurus (RO), pre-Bötzinger complex (PreBötC)] and non-chemosensory area [hypoglossal nucleus (XII), inferior olive nucleus (IO)]. Kir4.1 immunoreactivity was observed in the glial cells and neuropil, especially in XII and IO. Kir5.1 immunoreactivity was observed in the nerve cell bodies in the XII, RO, and PreBötC, but not in the NTS or IO. In the NTS, a dense network of varicose nerve fibers showed immunoreactivity for Kir5.1. Our findings suggest that Kir channels may not act specific to the central chemoreception, but regulate the ionic properties of cellular membranes in various neurons and glial cells. KEY WORDS: chemoreceptor, hypercapnic acidosis, inwardly rectifying K + channel, medulla oblongata.

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Neurochemical development of brain stem nuclei involved in the control of respiration

Cited by 110 publications

References 120 publications

Postnatal development of metabolic rate during normoxia and acute hypoxia in rats: implication for a sensitive period

Postnatal development of metabolic rate during normoxia and acute hypoxia in rats: implication for a sensitive period

The ventilatory response to hypoxia and hypercapnia is absent in the neonatal fat-tailed dunnart

Immunohistochemical Distribution of Inwardly Rectifying K+ Channels in the Medulla Oblongata of the Rat

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