| Background and ObjectiveAs one of the environmental stresses in plateau, hypoxia is different from other stress factors. Due to the lower oxygen pressure, it can lead to oxygen deficiency in the whole organism, tissues and cells, and consequently cause a series of physiological and pathological changes. Our lab has previously reported that gestational intermittent hypoxia induced anxiety-like behavior in adult male offsprings of rats, and it was highly related to the upregulation and methylation of Corticotrophin-releasing factor receptor1(CRFRI) in PVN. Hypoxia not only affects physiological functions, but also influences emotional behaviors. This study mainly fouses on whether continuous hypoxia stress can induce anxiety-like behavior of adult rats, and analyzes gene expression of neuropeptides Angiotensin Ⅱ (Ang Ⅱ), Endothelin-1(ET-1) and Neuregulin1Ⅱ (NRG1 Ⅱ) and their receptors in behavior related nucleus to explore the possible regulatory mechanism.Research Design and MethodsWe used hypobaric chamber simulating hypoxia at5000m altitude to investgate the effect of5days continuous hypoxia on adult male rats’behavior. Open field test, light-dark box test and elevated plus maze test were performed to test whether hypoxia can induce rat anxiety-like behavior. Using microtome, nuclei of anterior cortex (AC), paraventricular nucleus (PVN), central nucleus of the amygdala (CeA), hippocampus (HP) and locus coeruleus (LC) were micropunched according to the stereotaxic coordinates of rat brain map. After extracting and reverse-transcribing the RNA from those nuclei, quantitative real-time PCR was performed to detect gene expression level of neuropeptides Ang Ⅱ, ET-1and NRG1Ⅱ and their receptors. Rat brain samples were collected immediately after hypoxia or after1day recovery.Results1. Hypoxia at a simulated altitude of5000m for5days significantly reduced the body weight of adult male rats, which didn’t return to control after recovery1day in normxia.2. Compared with control, continuous hypoxia of5000m for5days didn’t change the total distance, distance and time spent in the center or corners in open field test (5min and10min recording time). In light-dark box test, the latency of the first entry into the dark box was significantly lower and time spent in the light compartment was markedly decreased in hypoxia stressed group. In elevated plus maze test, the total entries and the entries to closed arms or to open arms were significantly decreased in hypoxia group, and the percentage of time spent in the close arms was significantly increased in hypoxia stressed group. Those results implied continuous hypoxia of5000m for5days didn’t change basic sport ability of adult male rats, but induced anxiety-like behavior of rat.3. Hypoxia of5000m for5days significantly induced CRFR1mRNA expression in AC, PVN and CeA, and it didn’t return to the control level in PVN and CeA after1day recovery after hypoxia.4.5000m continuous hypoxia for5days markedly increased AGT expression in AC and CeA, and the expression level of ATI a and AT2in PVN, CeA and HP were significantly upregulated in hypoxia stressed rats. After1day recovery after hypoxia, AT la and AT2expression level were still higher than control.5.5000m continuous hypoxia for5days didn’t change ET-1expression, which was significantly upregulated in AC, PVN, CeA, HP and LC of1day recovery group. Continuous hypoxia significantly increased ErA expression in those nuclei, and the expression of ErB only increased in PVN and CeA.6.5000m continuous hypoxia for5days didn’t affect NRG1Ⅱ and ErbB4expression in PVN, HP and LC, but increased in AC and CeA.SummaryIn conclusion, continuous exposure to5000m hypoxia for5days markedly reduced body weight and induced anxiety-like behavior of adult male rats, and upregulated neuropeptides Ang-Ⅱ ET-1and NRG Ⅲ expression in the nuclei of AC, PVN, CeA. These results suggest that these neuropeptides might differentially modulate neurocircuits that were associated with mood disorders, and induce anxiety-like behavior in adult male rats. |
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