Effects of DAPT on learning and memory abilities and the regulation of Notch signaling pathway in cerebral ischemia-reperfusion injury mice

doi:10.16098/j.issn.0529-1356.2018.02.003

Abstract

Abstract:

Objective To study the effect of DAPT on learning and memory abilities and the regulation of Notch signaling pathway in the cerebral ischemia-reperfusion injury mice. Methods A total of 140 health male mice were randomly divided into the sham group, the ischemia-reperfusion (I/R) group, and the DAPT group. Each group was subdivided into the 3 days, 7 days and 14 days subgroups. The learning and memory abilities were detected by Y-maze at one day before execution. Infarct volume was detected by triphenyltetrazolium chloride staining. The colorimetric method was used to detect the superoxide dismutase (SOD) and malondialdehyde (MDA) content. The morphological structures and Hes1 immunopositive cells in the hippocampal CA3 area were observed under a light microscope. Quantitative analysis was performed by cell morphometric technique. The expression of Hes5 protein was detected by Western blotting. Results Compared with the sham group, the learning and memory abilities of both the I/R group and the DAPT group were obviously improved and the SOD activity was significantly increased, but the contents of MDA were decreased (P＜0.05). After DAPT treatment, the SOD activity was obviously decreased, nevertheless the contents of MDA were increased in the DAPT group(P＜0.05).Under a light microscope, the neurons in the hippocampal CA3 area in the sham group were normal, but the neurons of the I/R group were showed cell edema, the dyeing depth, and loose arrangement, and the large number of neurons losed. The number of neurons in DAPT group increased and the staining became shallower. Compared with the sham group, the quantity of Hes1 immunopositive neurons and the expression of Hes5 protein were obviously improved in both the I/R group and the DAPT group. Compared with the I/R group, the expressions of Hes1 and Hes5 in DAPT group were decreased(P＜0.05). Conclusion DAPT can significantly reduce cerebral ischemia-reperfusion injury，which is closely related to the activation of Notch signaling pathway.

Key words: DAPT, Cerebral ischemia-reperfusion injury, Notch signaling pathway, Hes1, Hes5, Western blotting, Mouse

WANG Jun-jie ZHANG Xian-hu ZHU Jun-de GE Guo KANG Chao-sheng. Effects of DAPT on learning and memory abilities and the regulation of Notch signaling pathway in cerebral ischemia-reperfusion injury mice[J]. Acta Anatomica Sinica, 2018, 49(2): 151-157.

References

［1］ Sadana P, Coughlin L, Burke J, et al. Anti-edema action of thyroid hormone in MCAO model of ischemic brain stroke: Possible association with AQP4 modulation ［J］. J Neurol Sci, 2015, 354(1-2): 37-45.

［2］Artavanistsakonas S, Rand MD, Lake RJ. Notch signaling: cell fate control and signal integration in development ［J］. Science, 1999, 284(5415): 770-716.

［3］Li Z, Wang J, Zhao C, et al. Acute blockage of Notch signaling by DAPT induces neuroprotection and neurogenesis in the neonatal rat brain after stroke ［J］. Transl Stroke Res, 2016, 7(2): 132-140.

［4］Zhang X, Huang G, Liu H, et al. Folic acid enhances Notch signaling, hippocampal neurogenesis, and cognitive function in a rat model of cerebral ischemia ［J］. Nutr Neurosci, 2012, 15(2): 55-61.

［5］Fiuza UM, Arias AM. Cell and molecular biology of Notch ［J］. J Endocrinol, 2007, 194(3): 459-474.

［6］Lee ML, MartinezLozada Z, Krizman EN, et al. Brain endothelial cells induce astrocytic expression of the glutamate transporter GLT-1 by a Notch-dependent mechanism ［J］. J Neurochem, 2017, 143(5):489-506.

［7］Koizumi J, Yoshid Y, Nakazawa T, et al. Experimental studies of ischemia brain edema: a new experimental model of cerebral embolism in rats in which recirculation can be introduced in the ischemia area ［J］. Stroke, 1986, 8(1): 1-8.

［8］Yang QZ. The role of Notch signaling pathway in the neuroprotection induced by sevoflurane ［D］. Xi’an: Fourth Military Medical University, 2011: 45-47.(in Chinese)

杨谦梓. Notch信号通路在七氟烷预处理诱导脑缺血耐受中的作用及机制研究［D］. 西安：第四军医大学, 2011: 45-47.

［9］Longa EZ, Weinstein PR, Carlson S, et al. Reversible middle cerebral artery occlusion without craniectomy in rats ［J］. Stroke, 1989, 20(1): 84-91.

［10］Stapf C, Mohr JP. Ischemic stroke therapy ［J］. Annu Rev Med, 2002, 53: 453-475.

［11］Kontos HA. Oxygen radicals in cerebral ischemia: the 2001 Willis lecture ［J］. Stroke, 2001, 32(11): 2712-2716.

［12］Zhu JD, Xiao ChL, Yu ZJ, et al. Protection of melatonin on learning and memory and neurons in the hippocampal CA3 area of Alzheimer’s disease model rats ［J］. Acta Anatomica Sinica, 2011, 42(4): 441-445.(in Chinese)

朱俊德，肖朝伦，余资江，等. 褪黑素对阿尔茨海默病模型大鼠学习记忆能力及海马CA3区神经元的保护作用［J］. 解剖学报, 2011, 42(4): 441-445.

［13］Lainiola M, Procaccini C, Linden AM. mGluR3 knockout mice show a working memory defect and an enhanced response to MK-801 in the T-and Y-maze cognitive tests ［J］. Behav Brain Res, 2014, 266(11): 94-103.

［14］Eghwrudjakpor PO, Allison AB. Oxidative stress following traumatic brain injury: enhancement of endogenous antioxidant defense systems and the promise of improved outcome ［J］. Niger J Med, 2010, 19(1): 14-21.

［15］Pei H, Cao D, Guo Z, et al. Bone morphogenetic protein-7 ameliorates cerebral ischemia and reperfusion injury via inhibiting oxidative stress and neuronal apoptosis ［J］. Int J Mol Sci, 2013, 14(12): 23441-23453.

［16］Xiaoping Du, Wei Li, Xinsheng Gao, et al. Regeneration of mammalian cochlear and vestibular hair cells through Hes1/Hes5 modulation with siRNA ［J］. Hear Res, 2013, 304(7): 91-110.

［17］Cao Y, Cai J, Zhang S, et al. Autophagy sustains hematopoiesis through targeting Notch ［J］. Stem Cells Dev, 2015, 24 (22): 2660-2673.

［18］Evin G, Sernee MF, Masters CL. Inhibition of gamma-secretase as a therapeutic intervention for Alzheimer’s disease: prospects, limitations and strategies ［J］. CNS Drugs, 2006, 20(5): 351-372.

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