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Sleep Disorders: Sleep Disorders: Effects of Intermittent Hypoxia |

Role of Hippocampal Neuronal Excitatory Synaptic Transmission Changes in Modulating Neurocognitive Impairments in a Mouse Model of Chronic Intermittent Hypoxia FREE TO VIEW

Rui Chen, PhD; Jing Ju; Ting Li
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Second Affiliated Hospital of Soochow University, Suzhou, China


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2016;149(4_S):A557. doi:10.1016/j.chest.2016.02.582
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SESSION TITLE: Sleep Disorders: Effects of Intermittent Hypoxia

SESSION TYPE: Original Investigation Slide

PRESENTED ON: Sunday, April 17, 2016 at 04:00 PM - 05:00 PM

PURPOSE: To investigate the role of neuronal excitatory synaptic transmission abnormal and NR2B and BDNF expression dysregulation in modulating neurocognitive impairments in a mouse model of chronic intermittent hypoxia.

METHODS: ICR male mice were randomly divided into three groups, the control group (UC+VEH group, n=10), CIH exposure group (CIH+VEH group, n=10) and CIH exposure pretreated with memantine group (CIH+MEM group, n=10). CIH group were exposed to intermittent hypoxia while UC mice to room air for 8 h per day during 2 weeks. Mice in the CIH+MEM group were pretreated with memantine (5mg/kg) by intraperitoneal injection in approximately 15 minutes prior to starting daily CIH exposure, and the other two groups were treated with same volume of saline. Using the whole cell patch clamp technique to evaluate the changes of hippocampal neuronal spontaneous excitatory postsynaptic currents and the electrophysiological characteristics, the western blotting method to detect the expression of NR2B and BDNF in hippocampus.

RESULTS: Compared with the UC+VEH group, exposed to 2-week CIH enhanced the frequency and the amplitude of sEPSC in hippocampal CA1 neurons (P<0.05). There were a increased neuronal spike threshold (-43.30±3.70mV vs. -40.37±3.46mV,P<0.05), and decreased average spike number (P<0.01) after given the same current stimulus in CIH+VEH mice. The exposure to CIH also significantly up-regulated the expression of NR2B (P<0.01), and down-regulated the expression of BDNF (P<0.05). In contrast, pre-treatment with memantine significantly recovered the electrophysiological characteristics of hippocampal CA1 neuron, decreased the frequency and the amplitude of sEPSC (P<0.05). Meanwhile, such CIH-induced changes of NR2B and BDNF expression were abolished in CIH group pretreated with memantine compared to the CIH+VEH group (P<0.01 or P<0.05).

CONCLUSIONS: CIH induces excitatory synaptic transmission abnormal, decreases neuronal excitability; and dysregulates NMDAR mediated signaling pathway. This effect may play an important role in CIH-induced neurocognitive impairments.

CLINICAL IMPLICATIONS: CIH is commonly seen in patients with obstructive sleep apnea, and has been hypothesized to underlie the neurocognitive dysfunction in these patients. However, its cellular and molecular mechanisms remain to be defined. The present study aimed to investigate, in a mouse CIH model, the role of neuronal excitatory synaptic transmission abnormal and NR2B and BDNF expression dysregulation in modulating neurocognitive impairments.

DISCLOSURE: The following authors have nothing to disclose: Rui Chen, Jing Ju, Ting Li

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