N-乙酰半胱氨酸通过海马区Notch1/hes1通路改善丙戊酸孤独症模型鼠的学习和记忆能力

doi:10.13418/j.issn.1001-165x.2019.04.007

Abstract

Abstract: Objective　To investigate the effects of N-acetylcysteine (NAC) on learning and memory abilities, as well as the molecular mechanisms underlying the therapeutic roles in a valproic acid (VPA)-induced rat model of autism.　Methods　After prenatal exposure to VPA, the three-chamber test was used to identify the autism modeling, the expression of the signaling molecules of the Notch1/hes1 signaling pathway Notch1, Notch intracellular domain (NICD), Jagged1 and Hes1 in the hippocampus (HC) of autistic rats was determined using Western blot, the expression of Hes1 was determined using the immunohistochemical technique. Then, the roles of NAC in learning and memory abilities and the Notch1/hes1 signaling pathway in the VPA-induced autism model were investigated.　Results　Compared with the control group, VPA increased the time spent in finding the platform, decreased the number of crossing platform and the time spent in the platform. However, compared with the VPA group, VPA+NAC group lowered the time spent in finding the platform, increased the number of crossing platform and the time spent in the platform. Simultaneously, the expression levels of NICD and Hes1 in VPA+NAC group decreased in the HC of autism model, and NAC ameliorated learning and memory abilities in the autism model rats.　Conclusion　The beneficial effects of NAC in ameliorating learning and memory abilities of autism model may be mediated by attenuating the Notch1/hes1 pathway activity.

Key words: Autism; , , N-acetylcysteine; , , Valproic acid; , , Notch1; , , Learning and memory abilities

CLC Number:

R363.1

XIANG Zhe, ZHANG Ying-hua, HE Xue-ling, WANG Li-jun, CUI Wei-gang. N-acetylcysteine ameliorates learning and memory abilities via the Notch1/hes1 signaling pathway of the hippocampus in a valproic acid-induced rat model of autism [J]. Chinese Journal of Clinical Anatomy, 2019, 37(4): 390-396.

References 17

[1]	Marler S, Sanders KB, Veenstra-VanderWeele J. N-acetylcysteine as treatment for self-injurious behavior in a child with autism[J]. J Child Adolesc Psychopharmacol, 2014, 24(4): 231-234.
[2]	Stutzman D, Dopheide J. Acetylcysteine for treatment of autism spectrum disorder symptoms[J]. Am J Health Syst Pharm, 2015, 72(22): 1956-1959.
[3]	Chen YW, Lin HC, Ng MC, et al. Activation of mGluR2/3 underlies the effects of N-acetylcystein on amygdala-associated autism-like phenotypes in a valproate-induced rat model of autism[J]. Front Behav Neurosci, 2014, 8: 219.
[4]	陈亦岚, 文敏, 周波, 等. 孤独症大鼠前额叶皮质中Notch相关蛋白的表达[J]. 中国儿童保健杂志, 2016, 24(3): 260-263.
[5]	Wei J, Zhang L, Ren L, et al. Endosulfan inhibits proliferation through the Notch signaling pathway in human umbilical vein endothelial cells[J]. Environ Pollut, 2017, 221: 26-36.
[6]	Yao M, Gao F, Wang X, et al. Nox4 is involved in high glucose-induced apoptosis in renal tubular epithelial cells via Notch pathway[J]. Mol Med Rep, 2017, 15(6): 4319-4325.
[7]	Sosa-Díaz N, Bringas ME, Atzori M, et al. Prefrontal cortex, hippocampus, and basolateral amygdala plasticity in a rat model of autism spectrum[J]. Synapse, 2014, 68(10): 468-473.
[8]	Bailey A, Luthert P, Bolton P, et al. Autism and megalencephaly[J]. Lancet, 1993, 341(8854): 1225-1226.
[9]	Wang Z, Xu L, Zhu X, et al. Demethylation of specific Wnt/beta-catenin pathway genes and its upregulationin rat brain induced by prenatal valproate exposure[J]. Anat Rec (Hoboken), 2010, 293(11): 1947-1953.
[10]	Zhang Y, Cui W, Zhai Q, et al. N-acetylcysteine ameliorates repetitive/stereotypic behavior due to its antioxidant properties without activation of the canonical Wnt pathway in a valproic acid-induced rat model of autism[J]. Mol Med Rep, 2017, 16(2): 2233-2240.
[11]	Vulto-van Silfhout AT, de Brouwer AF, de Leeuw N, et al. A 380-kb duplication in 7p22.3 encompassing the LFNG gene in a boy with asperger syndrome[J]. Mol Syndromol, 2012, 2(6): 245-250.
[12]	Wise A, Tenezaca L, Fernandez RW, et al. Drosophila mutants of the autism candidate gene neurobeachin (rugose) exhibit neuro-developmental disorders, aberrant synaptic properties, altered locomotion, and impaired adult social behavior and activity patterns[J]. J Neurogenet, 2015, 29(2-3): 135-143.
[13]	Yatim A, Benne C, Sobhian B, et al. NOTCH1 nuclear interactome reveals key regulators of its transcriptional activity and oncogenic function[J]. Mol Cell, 2012, 48(3): 445-458.
[14]	Tuand K, Stijnen P, Volders K, et al. Nuclear localization of the autism candidate gene neurobeachin and functional interaction with the NOTCH1 intracellular domain indicate a role in regulating transcription[J]. PLoS One, 2016, 11(3): e0151954.
[15]	Niesmann K, Breuer D, Brockhaus J, et al. Dendritic spine formation and synaptic function require neurobeachin[J]. Nat Commun, 2011, 2: 557.
[16]	刘瑶, 赵晓云, 韩颖, 等. 脑缺血后处理对脑缺血再灌注大鼠Notch1信号通路及学习记忆功能的影响[J]. 中国医科大学学报, 2017, 46(11): 984-989.
[17]	Borghese L, Dolezalova D, Opitz T, et al. Inhibition of notch signaling in human embryonic stem cell-derived neural stem cells delays G1/S phase transition and accelerates neuronal differentiation in vitro and in vivo[J]. Stem Cells, 2010, 28(5): 955-964.

N-acetylcysteine ameliorates learning and memory abilities via the Notch1/hes1 signaling pathway of the hippocampus in a valproic acid-induced rat model of autism

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