Lung-injury depresses glutamatergic synaptic transmission in the nucleus tractus solitarii via discrete age-dependent mechanisms in neonatal rats

Sustained hypoxia (SH) activates chemoreceptors to produce cardiovascular and respiratory responses to bring the arterial partial pressure of O2 back to the physiological range. We evaluated the effect of SH (fraction of inspired O2 = 0.10, 24 h) on glutamatergic synaptic transmission and the interaction neuron-astrocyte in neurons of the nucleus tractus solitarii (NTS). Tractus solitarius (TS) fiber stimulation induced glutamatergic currents in neurons and astrocytes. SH increased α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate (AMPA/kainate) [−183 ± 122 pA ( n = 10) vs. −353 ± 101 pA ( n = 10)] and N-methyl-d-aspartate (NMDA) current amplitude [61 ± 10 pA ( n = 7) vs. 102 ± 37 pA ( n = 10)]. To investigate the effects of SH, we used fluoroacetate (FAC), an astrocytic inhibitor, which revealed an excitatory modulation on AMPA/kainate current and an inhibitory modulation of NMDA current in control rats. SH blunted the astrocytic modulation of AMPA [artificial cerebrospinal fluid (aCSF): −353 ± 101 pA vs. aCSF + FAC: −369 ± 76 pA ( n = 10)] and NMDA currents [aCSF: 102 ± 37 pA vs. aCSF + FAC: 108 ± 32 pA ( n = 10)]. SH increased AMPA current density [control: −6 ± 3.5 pA/pF ( n = 6) vs. SH: −20 ± 12 pA/pF ( n = 7)], suggesting changes in density, conductance, or affinity of AMPA receptors. SH produced no effect on astrocytic resting membrane potential, input resistance, and AMPA/kainate current. We conclude that SH decreased the neuron-astrocyte interaction at the NTS level, facilitating the glutamatergic transmission, which may contribute to the enhancement of cardiovascular and respiratory responses to baro- and chemoreflexes activation in SH rats. NEW & NOTEWORTHY Using an electrophysiological approach, we have shown that in nucleus tractus solitarii (NTS) from control rats, astrocytes modulate the AMPA and NMDA currents in NTS neurons, changing their excitability. Sustained hypoxia (SH) increased both glutamatergic currents in NTS neurons due to 1) a reduction in the astrocytic modulation and 2) an increase in the density of AMPA receptors. These new findings show the importance of neuron-astrocyte modulation in the excitatory synaptic transmission in NTS of control and SH rats.

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Acute lung injury in neonatal rats causes postsynaptic depression in nucleus tractus solitarii second-order neurons

Respiratory Physiology & Neurobiology ◽

10.1016/j.resp.2019.103250 ◽

2019 ◽

Vol 269 ◽

pp. 103250 ◽

Cited By ~ 2

Author(s):

Paulina M. Getsy ◽

Catherine A. Mayer ◽

Peter M. MacFarlane ◽

Frank J. Jacono ◽

Christopher G. Wilson

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Second Order ◽

Nucleus Tractus Solitarii ◽

Neonatal Rats

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GABAc receptor mediated modulation of glutamatergic synaptic transmission to amacrine cells in the mouse retina

Neuroscience Research ◽

10.1016/s0168-0102(00)81038-x ◽

2000 ◽

Vol 38 ◽

pp. S32

Author(s):

K Matsui

Keyword(s):

Synaptic Transmission ◽

Amacrine Cells ◽

Mouse Retina ◽

Glutamatergic Synaptic Transmission ◽

Gabac Receptor

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Spreading Depression (SD) Waves in the Brainstem of Immature Rats Propagate Independently of Glutamatergic Synaptic Transmission

Klinische Neurophysiologie ◽

10.1055/s-2004-832137 ◽

2004 ◽

Vol 35 (03) ◽

Author(s):

F Richter ◽

A Lehmenkuhler ◽

HG Schaible

Keyword(s):

Synaptic Transmission ◽

Spreading Depression ◽

Glutamatergic Synaptic Transmission ◽

Immature Rats

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Bidirectional modulation of glutamatergic synaptic transmission by mGlu7 receptors at Schaffer Collateral-CA1 hippocampal synapses

10.26226/morressier.5b31ec632afeeb001345a2fa ◽

2018 ◽

Author(s):

Ricardo Martín

Keyword(s):

Synaptic Transmission ◽

Schaffer Collateral ◽

Glutamatergic Synaptic Transmission ◽

Hippocampal Synapses ◽

Bidirectional Modulation

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Citalopram reduces glutamatergic synaptic transmission in the auditory cortex via activation of 5-HT1A receptors

Neuroreport ◽

10.1097/wnr.0000000000001366 ◽

2019 ◽

Vol 30 (18) ◽

pp. 1316-1322 ◽

Cited By ~ 2

Author(s):

Víctor Cervantes-Ramírez ◽

Martha Canto-Bustos ◽

Diana Aguilar-Magaña ◽

Elsy Arlene Pérez-Padilla ◽

José Luis Góngora-Alfaro ◽

...

Keyword(s):

Synaptic Transmission ◽

Auditory Cortex ◽

Glutamatergic Synaptic Transmission

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Consecutive daily administration of intratracheal surfactant and human umbilical cord-derived mesenchymal stem cells attenuates hyperoxia-induced lung injury in neonatal rats

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02335-4 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Hsiu-Chu Chou ◽

Chien-Hsiang Chang ◽

Chien-Han Chen ◽

Willie Lin ◽

Chung-Ming Chen

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Lung Injury ◽

Umbilical Cord ◽

Daily Administration ◽

Vascular Density ◽

Human Umbilical Cord ◽

Neonatal Rats ◽

Vegf Expression ◽

Intratracheal Administration

Abstract Background Surfactant therapy is a standard of care for preterm infants with respiratory distress and reduces the incidence of death and bronchopulmonary dysplasia in these patients. Our previous study found that mesenchymal stem cells (MSCs) attenuated hyperoxia-induced lung injury and the combination therapy of surfactant and human umbilical cord-derived MSCs (hUC-MSCs) did not have additive effects on hyperoxia-induced lung injury in neonatal rats. The aim is to evaluate the effects of 2 consecutive days of intratracheal administration of surfactant and hUC-MSCs on hyperoxia-induced lung injury. Methods Neonatal Sprague Dawley rats were reared in either room air (RA) or hyperoxia (85% O2) from postnatal days 1 to 14. On postnatal day 4, the rats received intratracheal injections of either 20 μL of normal saline (NS) or 20 μL of surfactant. On postnatal day 5, the rats reared in RA received intratracheal NS, and the rats reared in O2 received intratracheal NS or hUC-MSCs (3 × 104 or 3 × 105 cells). Six study groups were examined: RA + NS + NS, RA + surfactant + NS, O2 + NS + NS, O2 + surfactant + NS, O2 + surfactant + hUC-MSCs (3 × 104 cells), and O2 + surfactant + hUC-MSCs (3 × 105 cells). The lungs were excised for histological, western blot, and cytokine analyses. Results The rats reared in hyperoxia and treated with NS yielded significantly higher mean linear intercepts (MLIs) and interleukin (IL)-1β and IL-6 levels and significantly lower vascular endothelial growth factors (VEGFs), platelet-derived growth factor protein expression, and vascular density than did those reared in RA and treated with NS or surfactant. The lowered MLIs and cytokines and the increased VEGF expression and vascular density indicated that the surfactant and surfactant + hUC-MSCs (3 × 104 cells) treatment attenuated hyperoxia-induced lung injury. The surfactant + hUC-MSCs (3 × 105 cells) group exhibited a significantly lower MLI and significantly higher VEGF expression and vascular density than the surfactant + hUC-MSCs (3 × 104 cells) group did. Conclusions Consecutive daily administration of intratracheal surfactant and hUC-MSCs can be an effective regimen for treating hyperoxia-induced lung injury in neonates.

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