Therapeutic effect of neuregulin1β on the dysfunction of learning and memory in rats with chronic omethoate poisoning

doi:10.16098/j.issn.0529-1356.2015.06.005

Abstract

Abstract:

Objective To observe the effect of neuregulin1β (NRG1β) on the level of phosphorylated extracellular regulated protein kinase(ERK)1/2 (p-ERK1/2), and explore the therapeutic mechanism of NRG1β on the cognitive dysfunction in rats with chronic omethoate poisoning. Methods Rats with strong learning and memory ability were selected by Y-electric maze test to establish the cognitive impairment model by subcutaneous injection of omethoate［5mg/(kg·d)］ for 4 weeks. After the model was established, rats in the treatment group were injected with NRG1β into their ventricles. The cognitive capacity of rats was evaluated with Y-electric maze. The morphology and ultrastructure of hippocampus were observed by haematoxylin eosin (HE) staining and transmission electron microscopy (TEM) respectively. The expression of p-ERK1/2 was determined by immunohistochemical (IHC) staining and Western blotting. Results Y-electric maze test showed the cognitive ability in rats with omethoate exposed (model and treatment groups) reduced significantly compared with normal rats, but the ability of treated rats was improved obviously compared with that of model rats. In compare with normal rats, obvious injury of hippocampus was observed in the model group by HE staining and TEM, and the phosphorylation level of ERK1/2 decreased significantly. In the rats treated with NRG-1β, the injury was milder than the model rats, and the phosphorylation level of ERK1/2 increased significantly. Conclusion In the chronic omethoate poisoning rat, NRG-1β can promote the phosphorylation level of ERK1/2 in hippocampus, and may play an important role in the improvement of cognitive function.

Key words: Neuregulin 1β, Omethoate, Cognitive dysfunction, Extracellular regulated protein kinase, Western blotting, Rat

RONG Li-xia SUN Shan-shan DING Kun ZHANG Rui ZHANG Mei-zeng*. Therapeutic effect of neuregulin1β on the dysfunction of learning and memory in rats with chronic omethoate poisoning[J]. AAS, 2015, 46(6): 750-756.

References

［1］Costa LG. Current issues in organophosphate toxicology［J］. Clin Chim Acta, 2006, 366(1-2):1-13.
［2］Speed HE, Blaiss CA, Kim A, et al. Delayed reduction of hippocampal synaptic transmission and spines following exposure to repeated subclinical doses of organophosphorus pesticide in adult mice［J］. Toxicol Sci, 2012, 125(1):196-208.
［3］Ca?adas F, Cardona D, Dávila E, et al. Long-term neurotoxicity of chlorpyrifos: spatial learning impairment on repeated acquisition in a water maze［J］. Toxicol Sci, 2005, 85(2): 944-951.
［4］Padilla S, Marshall RS, Hunter DL, et al. Neurochemical effects of chronic dietary and repeated high-level acute exposure to chlorpyrifos in rats［J］. Toxicol Sci, 2005, 88(1):161-171.
［5］Rosenblum K, Futter M, Jones M, et al. ERK1/2 regulation by the muscarinic acetylcholine receptors in neurons［J］. J Neurosci, 2000, 20(3):977-985.
［6］Yan ChH, Jiao LF, Zhao J, et al. Chlorpyrifos caused spatial memory impairment and inhibition of the ERK/CREB signal system［J］. Military Medical Sciences, 2012, 36(5):341-344.（in Chinese）
闫长会, 焦利飞, 赵君, 等. 毒死蜱致大鼠空间记忆损伤及ERK/CREB信号途径抑制［J］. 军事医学, 2012, 36(5):341-344.
［7］Chen Y, Zhang M, Li Q, et al. Interfering effect and mechanism of neuregulin on experimental dementia models in rats［J］. Behav Brain Res, 2011, 222(2):321-325.
［8］Chen Y, Qin LH, Chen XP, et al. Interferring effect and probable mechanism of neuregulin on experimental dementia model in rats［J］. Acta Anatomica Sinica, 2010, 41(5): 666-669.（in Chinese）
陈燕，秦丽华，陈希平，等. 神经调节素对实验性痴呆大鼠的干预作用和可能机制［J］. 解剖学报，2010, 41(5): 666-669.
［9］Tian Q, Jia J, Qu XH, et al. Effect of neuregulin on expressions of apoptosis and nuclear factor kappa B in hippocampus of Alzheimer’s disease model rats［J］. Chinese Journal of Behavioral Medical and Brain Science, 2012, 21(1):26-29.（in Chinese）
田强，贾军，屈兴汉，等. 神经调节素对阿尔茨海默病大鼠模型海马细胞凋亡和核转录因子κB表达的影响［J］. 中华行为医学与脑科学杂志，2012, 21(1): 26-29.
［10］Min SS, An J, Lee JH, et al. Neuregulin-1 prevents amyloid β-induced impairment of long-term potentiation in hippocampal slices via ErbB4［J］. Neurosci Lett, 2011, 505(1):6-9.
［11］McCubrey JA, Steelman LS, Chappell WH, et al. Roles of the Raf/MEK/ERK pathway in cell growth, malign ant, transformation and drug resistance［J］. Biochim Biophys Acta, 2007, 1773(8):1263-1284.
［12］Eichenbaum H, Otto T, Cohen NJ. The hippocampus—what does it do［J］? Behav Neural Biol, 1992, 57(1): 2-36.
［13］English JD, Sweatt JD. A requirement for the mitogen-activated protein kinase cascade in hippocampal long term potentiation［J］. J Biol Chem, 1997, 272(31):19103-19106.
［14］Mazzucchelli C, Vantaggiato C, Ciamei A, et al. Knockout of ERK1 MAP kinase enhances synaptic plasticity in the striatum and facilitates striatal-mediated learning and memory ［J］. Neuron, 2002, 34(5):807-820.
［15］Houser CR, Huang CS, Peng Z. Dynamic seizure-related changes in extracellular signal-regulated kinase activation in a mouse model of temporal lobe epilepsy［J］. Neuroseienee, 2008, 156(1):222-237.
［16］Silva AJ, Frankland PW, Marowitz Z, et al. A mouse model for the learning and memory deficits associated with neurofibromatosis type 1［J］. Nat Genet, 1997, 15(3):281-284.
［17］Hebert AE, Dash P. K1 plasticity in the entorhinal cortex suppresses memory for contextual fear［J］. J Neuroeci, 2004, 24(45):101112-101161.
［18］Kim SW, Ha NY, Kim KI, et al. Memory-improving effect of formulation-MSS by activation of hippocampal MAPK/ERK signaling pathway in rats［J］. BMB Rep, 2008, 41(3):242-247. 
［19］Samudio-Ruiz SL, Allan AM, Valenzuela CF, et al. Prenatal ethanol exposure persistently impairs NMDA receptor-dependent activation of extracellular signal-regulated kinase in the mouse dentate gyrus［J］. J Neurochem, 2009, 109(5):1311-1323.
［20 ］Kelleher RJ, Govindarajan A, Jung HY, et al. Translational control by MAPK signaling in long-term synaptic plasticity and memory［J］. Cell, 2004, 116(3):467-479.

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