Danielson Matthew D, Antonelli Brielle J, Gonzalez Megan R, Bavis Ryan W
Department of Biology, Bates College, Lewiston, ME 04240, USA.
Department of Biology, Bates College, Lewiston, ME 04240, USA.
Respir Physiol Neurobiol. 2025 Aug-Sep;336:104440. doi: 10.1016/j.resp.2025.104440. Epub 2025 May 2.
Newborn rats have a biphasic hypoxic ventilatory response (HVR) that typically matures during the second postnatal week, but rats reared in moderate hyperoxia (30-60 % O) already exhibit a sustained increase in ventilation during the late-phase of the HVR by 3 days of age (P3). Enhanced glutamatergic neurotransmission through NMDA receptors contributes to both normal maturation of the HVR and hyperoxia-induced developmental plasticity, but the role of non-NMDA glutamate receptors is unclear. To investigate the involvement of non-NMDA glutamate receptors in respiratory control and hyperoxia-induced plasticity, newborn Sprague Dawley rats were exposed to 21 % O (Control) or 60 % O (Hyperoxia) until their HVR was measured by head-body plethysmography at P3-4. Systemic administration of the AMPA/kainate receptor antagonist NBQX (12.5 mg kg, i.p.) caused rats from both treatment groups to adopt a slower, deeper breathing pattern with a modest reduction in baseline minute ventilation and convection requirement. NBQX also attenuated the HVR measured during the first minute of hypoxia in both treatment groups, but it did not alter the overall shape of the HVR; Hyperoxia rats exhibited a sustained increase in ventilation throughout the entire 15-min exposure to 11 % O regardless of whether they received saline or NBQX injections, while Control rats had a strongly biphasic HVR. Therefore, glutamatergic neurotransmission via non-NMDA glutamate receptors plays an important role in the respiratory control of neonatal rats but not in the respiratory plasticity expressed after chronic postnatal hyperoxia.
新生大鼠具有双相性低氧通气反应（HVR），该反应通常在出生后第二周成熟，但在中度高氧环境（30 - 60% O₂）中饲养的大鼠在3日龄（P3）时，HVR后期的通气量就已持续增加。通过N-甲基-D-天冬氨酸（NMDA）受体增强的谷氨酸能神经传递有助于HVR的正常成熟和高氧诱导的发育可塑性，但非NMDA谷氨酸受体的作用尚不清楚。为了研究非NMDA谷氨酸受体在呼吸控制和高氧诱导的可塑性中的作用，将新生的斯普拉格-道利大鼠暴露于21% O₂（对照组）或60% O₂（高氧组）环境中，直到在P3 - 4时通过头身体积描记法测量它们的HVR。腹腔注射AMPA/海人酸受体拮抗剂NBQX（12.5 mg/kg），导致两个治疗组的大鼠呼吸模式变得更慢、更深，基线分钟通气量和对流需求略有降低。NBQX还减弱了两个治疗组在低氧第一分钟测量的HVR，但没有改变HVR的整体形状；无论高氧组大鼠接受的是盐水注射还是NBQX注射，在整个15分钟暴露于11% O₂的过程中，其通气量都持续增加，而对照组大鼠具有强烈的双相性HVR。因此，通过非NMDA谷氨酸受体的谷氨酸能神经传递在新生大鼠的呼吸控制中起重要作用，但在出生后慢性高氧后表现出的呼吸可塑性中不起作用。
