scholarly journals AMPA glutamate receptors and respiratory control in the developing rat: anatomic and pharmacological aspects

2000 ◽  
Vol 278 (2) ◽  
pp. R520-R528 ◽  
Author(s):  
Gina M. Whitney ◽  
Patricia J. Ohtake ◽  
Narong Simakajornboon ◽  
Ying-Dan Xue ◽  
David Gozal
Keyword(s):  
Brain Stem ◽  
Glutamate Receptors ◽  
Ampa Receptor ◽  
Age Groups ◽  
Respiratory Control ◽  
Receptor Expression ◽  
Whole Body ◽  
Ampa Glutamate Receptors ◽  
Rat Pups

The developmental role of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) glutamate receptors in respiratory regulation remains undefined. To study this issue, minute ventilation (V˙E) was measured in 5-, 10-, and 15-day-old intact freely behaving rat pups using whole body plethysmography during room air (RA), hypercapnic (5% CO2), and hypoxic (10% O2) conditions, both before and after administration of the non- N-methyl-d-aspartate (NMDA) receptor antagonist 1,2,3,4-tetrahydro-6-nitro-2,3-dioxobenzo[f]quinoxaline-7-sulfonamide disodium (NBQX; 10 mg/kg ip). In all age groups,V˙E during RA was unaffected by NBQX, despite reductions in breathing frequency ( f) induced by increases in both inspiratory and expiratory duration. During hypoxia and hypercapnia, V˙Eincreases were similar in both NBQX and control conditions in all age groups. However, tidal volume was greater and f lower after NBQX. To determine if AMPA receptor-positive neurons are recruited during hypoxia, immunostaining for AMPA receptor (GluR2/3) and c -fos colabeling was performed in caudal brain stem sections after exposing rat pups at postnatal ages 2, 5, 10, and 20 days, and adult rats to room air or 10% O2 for 3 h. GluR2/3 expression increased with postnatal age in the nucleus of the solitary tract (NTS) and hypoglossal nucleus, whereas a biphasic pattern emerged for the nucleus ambiguus (NA). c -fos expression was enhanced by hypoxia at all postnatal ages in the NTS and NA and also demonstrated a clear maturational pattern. However, colocalization of GluR2/3 and c -fos was not affected by hypoxia. We conclude that AMPA glutamate receptor expression in the caudal brain stem is developmentally regulated. Furthermore, the role of non-NMDA receptors in respiratory control of conscious neonatal rats appears to be limited to modest, albeit significant, regulation of breathing pattern.

scholarly journals What is the role of neurotransmitter systems in cortical seizures?

2008 ◽  
pp. S111-S120
Author(s):  
P Mareš ◽  
H Kubová
Keyword(s):  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Gabab Receptor ◽  
Age Groups ◽  
Gabab Receptors ◽  
Neurotransmitter Systems ◽  
Metabotropic Glutamate ◽  
Rat Pups ◽  
Epileptic Afterdischarges

Epileptic afterdischarges (ADs) elicited by electrical stimulation of sensorimotor cortical area were used as a model to study the role of neurotransmitter systems in cortical seizures in three age groups of developing rats. Drugs augmenting inhibition mediated by GABAA receptors were found to suppress ADs in all age groups, their activity was usually more marked in younger than in 25-day-old rat pups. Drugs potentiating GABAB receptors exhibit lower efficacy and more complicated developmental profile than GABAA-ergic drugs. Effects of an antagonist of GABAB receptor--marked prolongation of ADs in all three age groups--suggest an important role of GABAB receptors in arrest of cortical seizures. Drugs affecting glutamate receptors exhibit variable effects, usually better expressed in older animals than in 12-day-old ones. No specific role for ionotropic as well as metabotropic glutamate receptors could be predicted. Activation of adenosinergic inhibitory modulatory system also exhibited anticonvulsant action in the present model. All three neurotransmitter systems probably participate in mechanisms of generation, maintenance and arrest of cortical seizures.

Renal interstitial hyaluronan: functional aspects during normal and pathological conditions

2012 ◽  
Vol 302 (11) ◽  
pp. R1235-R1249 ◽  
Author(s):  
Sara Stridh ◽  
Fredrik Palm ◽  
Peter Hansell
Keyword(s):  
Current Knowledge ◽  
Stone Formation ◽  
Ischemia Reperfusion ◽  
The Body ◽  
Receptor Expression ◽  
Whole Body ◽  
Hydration Status ◽  
Hyaluronan Synthases ◽  
Pathological Conditions

The glycosaminoglycan (GAG) hyaluronan (HA) is recognized as an important structural component of the extracellular matrix, but it also interacts with cells during embryonic development, wound healing, inflammation, and cancer; i.e., important features in normal and pathological conditions. The specific physicochemical properties of HA enable a unique hydration capacity, and in the last decade it was revealed that in the interstitium of the renal medulla, where the HA content is very high, it changes rapidly depending on the body hydration status while the HA content of the cortex remains unchanged at very low amounts. The kidney, which regulates fluid balance, uses HA dynamically for the regulation of whole body fluid homeostasis. Renomedullary HA elevation occurs in response to hydration and during dehydration the opposite occurs. The HA-induced alterations in the physicochemical characteristics of the interstitial space affects fluid flux; i.e., reabsorption. Antidiuretic hormone, nitric oxide, angiotensin II, and prostaglandins are classical hormones/compounds involved in renal fluid handling and are important regulators of HA turnover during variations in hydration status. One major producer of HA in the kidney is the renomedullary interstitial cell, which displays receptors and/or synthesis enzymes for the hormones mentioned above. During several kidney disease states, such as ischemia-reperfusion injury, tubulointerstitial inflammation, renal transplant rejection, diabetes, and kidney stone formation, HA is upregulated, which contributes to an abnormal phenotype. In these situations, cytokines and other growth factors are important stimulators. The immunosuppressant agent cyclosporine A is nephrotoxic and induces HA accumulation, which could be involved in graft rejection and edema formation. The use of hyaluronidase to reduce pathologically overexpressed levels of tissue HA is a potential therapeutic tool since diuretics are less efficient in removing water bound to HA in the interstitium. Although the majority of data describing the role of HA originate from animal and cell studies, the available data from humans demonstrate that an upregulation of HA also occurs in diabetic kidneys, in transplant-rejected kidneys, and during acute tubular necrosis. This review summarizes the current knowledge regarding interstitial HA in the role of regulating kidney function during normal and pathological conditions. It encompasses mechanistic insights into the background of the heterogeneous intrarenal distribution of HA; i.e., late nephrogenesis, its regulation during variations in hydration status, and its involvement during several pathological conditions. Changes in hyaluronan synthases, hyaluronidases, and binding receptor expression are discussed in parallel.

scholarly journals Maternal dietary tryptophan deficiency alters cardiorespiratory control in rat pups

2011 ◽  
Vol 110 (2) ◽  
pp. 318-328 ◽  
Author(s):  
Eliana M. Penatti ◽  
Alexis E. Barina ◽  
Sharat Raju ◽  
Aihua Li ◽  
Hannah C. Kinney ◽  
...  
Keyword(s):  
Brain Stem ◽  
Sudden Infant Death ◽  
Normal Weight ◽  
Sudden Infant ◽  
Postnatal Life ◽  
Cardiorespiratory Control ◽  
Cardiorespiratory Function ◽  
Rat Pups ◽  
Neuronal Number

Malnutrition during pregnancy adversely affects postnatal forebrain development; its effect upon brain stem development is less certain. To evaluate the role of tryptophan [critical for serotonin (5-HT) synthesis] on brain stem 5-HT and the development of cardiorespiratory function, we fed dams a diet ∼45% deficient in tryptophan during gestation and early postnatal life and studied cardiorespiratory variables in the developing pups. Deficient pups were of normal weight at postnatal day (P)5 but weighed less than control pups at P15 and P25 ( P < 0.001) and had lower body temperatures at P15 ( P < 0.001) and P25 ( P < 0.05; females only). Oxygen consumption (V̇o2) was unaffected. At P15, deficient pups had an altered breathing pattern and slower heart rates. At P25, they had significantly lower ventilation (V̇e) and V̇e-to-V̇o2 ratios in both air and 7% CO2. The ventilatory response to CO2 (% increase in V̇e/V̇o2) was significantly increased at P5 (males) and reduced at P15 and P25 (males and females). Deficient pups had 41–56% less medullary 5-HT ( P < 0.01) compared with control pups, without a difference in 5-HT neuronal number. These data indicate important interactions between nutrition, brain stem physiology, and age that are potentially relevant to understanding 5-HT deficiency in the sudden infant death syndrome.

scholarly journals Alterations of the rewarding actions of amphetamine by prior nicotine and alcohol treatment: The role of age and dopamine

2020 ◽  
Author(s):  
Andrea Stojakovic ◽  
Syed Muzzammil Ahmad ◽  
Kabirullah Lutfy
Keyword(s):  
Glutamate Receptors ◽  
Age Groups ◽  
Alcohol Exposure ◽  
Female Adolescent ◽  
D1 Receptors ◽  
Dopaminergic Neurotransmission ◽  
Adult Mice ◽  
State Dependent ◽  
Drug Free

AbstractRationaleNicotine and alcohol each can serve as the gateway to other drugs.ObjectiveThe current study was sought to determine if prior nicotine and alcohol exposure alters amphetamine reward and if age and dopaminergic neurotransmission are involved.MethodsMale and female adolescent and adult C57BL/6J mice were tested for baseline place preference, received six conditioning with saline/nicotine (0.25 mg/kg) twice daily followed by six conditioning with saline/ethanol (2 g/kg) in a counterbalance manner. Control mice were conditioned with saline/saline throughout. Finally, mice were conditioned with amphetamine (3 mg/kg) once in the nicotine-alcohol-paired chamber and then tested for CPP 24 h later. The following day, mice were challenged with amphetamine (1 mg/kg) and tested for CPP under a drugged state. Mice were then immediately euthanized, brain removed and nucleus accumbens isolated and processed for the expression of dopamine receptors and transporter, and glutamate receptors.ResultsWe observed a greater amphetamine-induced CPP in adolescent than adult mice but no change in state-dependent CPP between the two age groups. In contrast, amphetamine-induced CPP in mice with prior nicotine-alcohol exposure was greater in adult than adolescent mice under both drug-free and drugged states. The enhanced response in adult mice was associated with greater expression of dopamine-transporter, reduced D2 receptors, and increased D1 receptors with no changes in glutamate receptors.ConclusionsThese results suggest that prior nicotine and alcohol exposure differentially alters the rewarding action of amphetamine in adult and adolescent mice and alterations in dopaminergic neurotransmission may be involved in this phenotype.

scholarly journals Membrane progesterone receptor-β, but not -α, in dorsal brain stem establishes sex-specific chemoreflex responses and reduces apnea frequency in adult mice

2016 ◽  
Vol 121 (3) ◽  
pp. 781-791 ◽  
Author(s):  
Ryma Boukari ◽  
Orlane Rossignol ◽  
Cécile Baldy ◽  
François Marcouiller ◽  
Aida Bairam ◽  
...  
Keyword(s):  
Brain Stem ◽  
Progesterone Receptors ◽  
Respiratory Control ◽  
Staining Intensity ◽  
Whole Body ◽  
Male And Female ◽  
Female Mice ◽  
Adult Mice ◽  
Specific Effects ◽  
Membrane Progesterone Receptor

We tested the hypothesis that membrane progesterone receptors (mPR) contribute to respiratory control in adult male and female mice. Mice were implanted with osmotic minipumps for continuous infusion of small interfering RNA (siRNA) directed against mPRα, mPRβ, or a control solution in the fourth ventricle (to target brain stem respiratory areas) for 14 days. We then performed respiratory and metabolic recordings by whole body plethysmography at rest and in response to hypoxia (12% O2) or hypercapnia (5% CO2, 5 min each). For each treatment, we have verified with immunohistochemistry that the staining intensity of mPRα or mPRβ in the brain stem is decreased. At rest, the siRNA against mPRα and mPRβ increased respiratory frequency in males only. The siRNA against mPRβ almost tripled the frequency of apneas in male and in female mice, while the siRNA against mPRα had no effect. Regarding respiratory chemoreflex, the siRNA against mPRβ suppressed the response to hypoxia in male and female mice and reduced by ∼50% the response to hypercapnia, while the siRNA against mPRα had more limited effects. Interestingly, control females had higher ventilatory response to hypoxia and hypercapnia than males, and these sex-specific effects were suppressed by the siRNA against mPRβ, whereas they were still present after treatment with the siRNA against mPRα. We conclude that mPRβ reduces apnea frequency in male and female mice and establishes sex-specific ventilatory chemoreflex.

Role of AMPA glutamate receptors in the conditioned rewarding effects of MDMA in mice

2018 ◽  
Vol 347 ◽  
pp. 57-60 ◽  
Author(s):  
M.P. García-Pardo ◽  
J. Miñarro ◽  
M.A. Aguilar
Keyword(s):  
Glutamate Receptors ◽  
Ampa Glutamate Receptors

Disruption of adenosinergic modulation of ventilation at rest and during hypercapnia by neonatal caffeine in young rats: role of adenosine A1 and A2A receptors

2007 ◽  
Vol 292 (4) ◽  
pp. R1621-R1631 ◽  
Author(s):  
Gaspard Montandon ◽  
Richard Kinkead ◽  
Aida Bairam
Keyword(s):  
Developmental Plasticity ◽  
Respiratory Control ◽  
Long Term Effects ◽  
Water Control ◽  
A2a Receptors ◽  
Rat Pups ◽  
Freely Behaving ◽  
Hypercapnic Response

Caffeine is commonly used to treat respiratory instabilities related to prematurity. However, the role of adenosinergic modulation and the potential long-term effects of neonatal caffeine treatment (NCT) on respiratory control are poorly understood. To address these shortcomings, we tested the following hypotheses: 1) adenosine A1- and A2A-receptor antagonists modulate respiratory activity at rest and during hypercapnia; 2) NCT has long-term consequences on adenosinergic modulation of respiratory control. Rat pups received by gavage either caffeine (15 mg/kg) or water (control) once a day from postnatal days 3 to 12. At day 20, rats received intraperitoneal injection with vehicle, DPCPX (A1 antagonist, 4 mg/kg), or ZM-241385 (A2A antagonist, 1 mg/kg) before plethysmographic measurements of resting ventilation, hypercapnic ventilatory response (5% CO2), and occurrence of apneas in freely behaving rats. In controls, data show that A2A, but not A1, antagonist decreased resting ventilation by 31% ( P = 0.003). A1 antagonist increased the hypercapnic response by 60% ( P < 0.001), whereas A2A antagonist increased the hypercapnic response by 42% ( P = 0.033). In NCT rats, A1 antagonist increased resting ventilation by 27% ( P = 0.02), but the increase of the hypercapnic response was blunted compared with controls. A1 antagonist enhanced the occurrence of spontaneous apneas in NCT rats only ( P = 0.005). Finally, A2A antagonist injected in NCT rats had no effect on ventilation. These data show that hypercapnia activates adenosinergic pathways, which attenuate responsiveness (and/or sensitivity) to CO2 via A1 receptors. NCT elicits developmental plasticity of adenosinergic modulation, since neonatal caffeine persistently decreases ventilatory sensitivity to adenosine blockers.

Episodic hypoxia enhances late hypoxic ventilation in developing rat: putative role of neuronal NO synthase

1999 ◽  
Vol 276 (1) ◽  
pp. R17-R22 ◽  
Author(s):  
David Gozal ◽  
Evelyne Gozal
Keyword(s):  
Brain Stem ◽  
Respiratory Control ◽  
No Synthase ◽  
Whole Body ◽  
Western Blots ◽  
Excitatory Neurotransmitter ◽  
Neuronal No Synthase ◽  
Episodic Hypoxia ◽  
Developing Rat ◽  
Nnos Expression

Nitric oxide (NO) is an excitatory neurotransmitter in the hypoxic ventilatory response (HVR). Furthermore, neuronal NO synthase (nNOS) activity in the developing rat correlates with the magnitude of late hypoxic ventilatory depression. To test the hypothesis that repeated short exposures to hypoxia may modify late HVR characteristics in young rats, we conducted 30-min hypoxic challenges in 2- to 3-day-old rat pups, before (Pre) and 6 h after (Post) they completed a series of eight cycles consisting of 5 min of hypoxia and 10 min of normoxia (Hyp-Norm) or normoxia throughout (Norm-Norm). In an additional group, similar challenges were performed after administration of either intraperitoneal vehicle or 25 mg/kg 7-nitroindazole (7-NI). Ventilation (V˙e) was measured using whole body plethysmography. Although no changes in peakV˙e responses occurred with episodic hypoxia (Pre vs. Post, P = not significant), lateV˙e reductions were markedly attenuated in Post (ΔV˙e from early to late: 7.2 ± 1.5 ml/min in Pre vs. 4.5 ± 1.1 ml/min in Post; P < 0.002). Furthermore, 7-NI treatment of Post animals was associated with lateV˙e reductions to Pre levels in Hyp-Norm-exposed animals. Western blots of protein equivalents from the caudal brain stem revealed increased nNOS expression in Hyp-Norm compared with Norm-Norm ( P < 0.01). Current findings suggest that repeated short hypoxic exposures improve the ability to sustain V˙e, which appears to be mediated by increased nNOS expression and activity in brain stem respiratory regions. We postulate that changes in nNOS may play a role in respiratory control plasticity.

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