Bin Peng1, Du-Du Hao1, Xia Li1, Guo-Hua Wang1, Zong-Yu Guan1, Zheng-Lin Jiang1,2. 1. Department of Neurophysiology and Neuropharmacology, Institute of Special Environmental Medicine and Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu, China. 2. Corresponding author: Department of Neurophysiology and Neuropharmacology, Institute of Special Environmental Medicine, Nantong University, 9 Seyuan Road, Chongchuan District, Nantong, Jiangsu 226019, China, jiangzl@ntu.edu.cn.
Abstract
INTRODUCTION: When humans breathe compressed air or N2-O2 mixtures at three to four atmospheres pressure, they will experience nitrogen narcosis that may possibly lead to a diving accident, but the underlying mechanisms remain unclear. METHODS: Mice were exposed to 1.6 MPa breathing a N2-O2 mixture adjusted to deliver an inspired PO2 of 32-42 kPa. The electroencephalogram (EEG) and forced swimming test were used to evaluate the narcotic effect of nitrogen. Neuronal activity was observed via c-Fos expression in cortex and hippocampus tissue after decompressing to the surface. To further investigate underlying molecular mechanisms, we incubated cultured hippocampal neurons with various NMDA concentrations, and measured expression of NMDA receptors and its down-stream signal with or without 1.6 MPa N2-O2 exposure. RESULTS: Both the frequency of the EEG and the drowning time using the forced swimming test were significantly decreased during exposure to 1.6 MPa N2-O2 (P < 0.001). Additionally, in cultured hippocampal neurons, the increased levels of phosphorylated NR2B and cAMP-response element binding protein (CREB) induced by NMDA stimulation were significantly inhibited by exposure to 1.6 MPa N2-O2. CONCLUSIONS: Our findings indicated that NR2B-containing NMDA receptors were inhibited during nitrogen narcosis. Copyright: This article is the copyright of the authors who grant Diving and Hyperbaric Medicine a non-exclusive licence to publish the article in electronic and other forms.
INTRODUCTION: When humans breathe compressed air or N2-O2 mixtures at three to four atmospheres pressure, they will experience nitrogennarcosis that may possibly lead to a diving accident, but the underlying mechanisms remain unclear. METHODS:Mice were exposed to 1.6 MPa breathing a N2-O2 mixture adjusted to deliver an inspired PO2 of 32-42 kPa. The electroencephalogram (EEG) and forced swimming test were used to evaluate the narcotic effect of nitrogen. Neuronal activity was observed via c-Fos expression in cortex and hippocampus tissue after decompressing to the surface. To further investigate underlying molecular mechanisms, we incubated cultured hippocampal neurons with various NMDA concentrations, and measured expression of NMDA receptors and its down-stream signal with or without 1.6 MPa N2-O2 exposure. RESULTS: Both the frequency of the EEG and the drowning time using the forced swimming test were significantly decreased during exposure to 1.6 MPa N2-O2 (P < 0.001). Additionally, in cultured hippocampal neurons, the increased levels of phosphorylated NR2B and cAMP-response element binding protein (CREB) induced by NMDA stimulation were significantly inhibited by exposure to 1.6 MPa N2-O2. CONCLUSIONS: Our findings indicated that NR2B-containing NMDA receptors were inhibited during nitrogennarcosis. Copyright: This article is the copyright of the authors who grant Diving and Hyperbaric Medicine a non-exclusive licence to publish the article in electronic and other forms.
Authors: Janne Grønli; William C Clegern; Michelle A Schmidt; Rahmi S Nemri; Michael J Rempe; Amelia L Gallitano; Jonathan P Wisor Journal: Sleep Date: 2016-12-01 Impact factor: 5.849