CIH-induced neurocognitive impairments are associated with hippocampal Ca2+ overload, apoptosis, and dephosphorylation of ERK1/2 and CREB that are mediated by overactivation of NMDARs

Wang, Jing; Hong, Ming; Chen, Rui; Ju, Jingmei; Peng, Wanda; Zhang, Guoxing; Liu, Chun‐Feng

doi:10.1016/j.brainres.2015.08.012

Cited by 27 publications

(19 citation statements)

References 45 publications

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“…This study found that hypoxic exposure stimulates the generation of ROS, which is coincident with OSAS and the animal model of the disorder 33, 34 . ROS includes superoxide anion, hydrogen peroxide and hydroxyl radical, and plays a physiological role in the function of a number of cellular signaling pathways 35 .…”

Section: Discussionmentioning

confidence: 60%

Genistein Protects Genioglossus Myoblast Against Hypoxia-induced Injury through PI3K-Akt and ERK MAPK Pathways

Ding

Chen

Wen

et al. 2017

Sci Rep

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Obstructive sleep apnea and hypopnea syndrome (OSAHS) is a clinical syndrome characterized by recurrent episodes of obstruction of the upper airway during sleep that leads to a hypoxic condition. Genioglossus, an important pharyngeal muscle, plays an important role in maintaining an open upper airway for effective breathing. Our previous study found that genistein (a kind of phytoestrogen) protects genioglossus muscle from hypoxia-induced oxidative injury. However, the underlying mechanism is still unknown. In the present study, we examined the effects of hypoxia on genioglossus myoblast proliferation, viability and apoptosis, and the protective effect of genistein and its relationship with the PI3K/Akt and ERK MAPK pathways. Cell viability and Bcl-2 were reduced under hypoxic condition, while ROS generation, caspase-3, MDA, and DNA damage were increased following a hypoxia exposure. However, the effects of hypoxia were partially reversed by genistein in an Akt- and ERK- (but not estrogen receptor) dependent manner. In conclusion, genistein protects genioglossus myoblasts against hypoxia-induced oxidative injury and apoptosis independent of estrogen receptor. The PI3K-Akt and ERK1/2 MAPK signaling pathways are involved in the antioxidant and anti-apoptosis effect of genistein on genioglossus myoblasts.

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Section: Discussionmentioning

confidence: 60%

Genistein Protects Genioglossus Myoblast Against Hypoxia-induced Injury through PI3K-Akt and ERK MAPK Pathways

Ding

Chen

Wen

et al. 2017

Sci Rep

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“…Then, the influx of a large amount of Ca 2+ into the extracellular fluid causes calcium overload in neurons, triggering a series of downstream pro-death signalling events, such as calpain activation, reactive oxygen species generation, and mitochondrial damage, further aggravating the symptoms of depression. [57][58][59] We detected the protein and mRNA expression of NMDAR subunits in hippocampal homogenates by Western blotting and q-PCR analysis. The results showed that the increased protein and mRNA expression of NR2B in the LPS group was reversed by electroacupuncture treatment.…”

Section: Dovepressmentioning

confidence: 99%

<p>Electroacupuncture Relieves LPS-Induced Depression-Like Behaviour in Rats Through IDO-Mediated Tryptophan-Degrading Pathway</p>

Zhang¹,

Liu²,

Gao³

et al. 2020

NDT

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Background: Neuroinflammation is an important pathological mechanism of depression that leads to an increase in indoleamine-2,3-dioxygenase (IDO) activity and NMDAR activation. This study aimed to observe the effects of electroacupuncture on depressionlike behaviour in lipopolysaccharide (LPS)-treated rats and the underlying mechanism. Methods: Wistar rats were intraperitoneally administered LPS (0.5 mg/kg) for 7 consecutive days to establish a depression model. Electroacupuncture treatment was administered 1 hour after daily LPS injection. The open field test (OFT), forced swimming test (FST), and sucrose preference test (SPT) were used to evaluate the depressive-like behaviours. IL-1β, IL-6, and TNF-α levels were determined by enzyme-linked immunosorbent assay (ELISA); Trp, 5-hydroxytryptamine (5-HT), kynurenine (Kyn) and quinolinic acid (Quin) were detected by ultra-high-performance liquid chromatography-tandem mass spectrometry; and N-methyl-D-aspartate receptor (NMDAR) protein and mRNA were assessed by Western blot and real-time qPCR. Results: The results showed that electroacupuncture treatment successfully corrected LPSinduced depressive-like behaviour, reduced the inflammatory factor (IL-1β, IL-6 and TNF-α) levels in the blood and hippocampus, prevented IDO over-activation and recovered NR2B expression after challenge by LPS. Conclusion: Electroacupuncture treatment provided protection against LPS-induced depressive-like behaviour, and the associated mechanisms may be related to inhibiting the inflammatory response, regulating the IDO-mediated tryptophan-degrading pathway, and inhibiting NR2B activation.

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“…One particular form of hypoxia, chronic intermittent hypoxia (CIH) may have specific detrimental effects on CNS function. CIH can lead to the over-activation of NMDARs, leading to an overload of intracellular Ca 2+ and a dephosphorylation of extracellular signal-regulated kinases (ERK) [ 27 ]. The CA1 region of the hippocampus is thought to be selectively vulnerable to CIH damage due to the high density of glutamate receptors located on its pyramidal neurons [ 28 ].…”

Section: Hypoxia and Synaptic Signalingmentioning

confidence: 99%

The Effects of Hypoxia and Inflammation on Synaptic Signaling in the CNS

Mukandala¹,

Tynan²,

Lanigan³

et al. 2016

Brain Sciences

117

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Normal brain function is highly dependent on oxygen and nutrient supply and when the demand for oxygen exceeds its supply, hypoxia is induced. Acute episodes of hypoxia may cause a depression in synaptic activity in many brain regions, whilst prolonged exposure to hypoxia leads to neuronal cell loss and death. Acute inadequate oxygen supply may cause anaerobic metabolism and increased respiration in an attempt to increase oxygen intake whilst chronic hypoxia may give rise to angiogenesis and erythropoiesis in order to promote oxygen delivery to peripheral tissues. The effects of hypoxia on neuronal tissue are exacerbated by the release of many inflammatory agents from glia and neuronal cells. Cytokines, such as TNF-α, and IL-1β are known to be released during the early stages of hypoxia, causing either local or systemic inflammation, which can result in cell death. Another growing body of evidence suggests that inflammation can result in neuroprotection, such as preconditioning to cerebral ischemia, causing ischemic tolerance. In the following review we discuss the effects of acute and chronic hypoxia and the release of pro-inflammatory cytokines on synaptic transmission and plasticity in the central nervous system. Specifically we discuss the effects of the pro-inflammatory agent TNF-α during a hypoxic event.

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CIH-induced neurocognitive impairments are associated with hippocampal Ca2+ overload, apoptosis, and dephosphorylation of ERK1/2 and CREB that are mediated by overactivation of NMDARs

Cited by 27 publications

References 45 publications

Genistein Protects Genioglossus Myoblast Against Hypoxia-induced Injury through PI3K-Akt and ERK MAPK Pathways

Genistein Protects Genioglossus Myoblast Against Hypoxia-induced Injury through PI3K-Akt and ERK MAPK Pathways

<p>Electroacupuncture Relieves LPS-Induced Depression-Like Behaviour in Rats Through IDO-Mediated Tryptophan-Degrading Pathway</p>

The Effects of Hypoxia and Inflammation on Synaptic Signaling in the CNS

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