Zhao Gang, Gao Jingquan, Liang Shuang, Wang Xuelai, Sun Caihong, Xia Wei, Hao Yanqiu, Li Xiang, Cao Yonggang, Wu Lijie
Department of Children's and Adolescent Health, Public Health College of Harbin Medical University, Harbin 150081, China.
Department of Nursing, Daqing Campus of Harbin Medical University, Daqing 163319, China.
Int J Dev Neurosci. 2015 Aug;44:14-21. doi: 10.1016/j.ijdevneu.2015.04.350. Epub 2015 Apr 24.
To investigate whether the decreased level of serum polyunsaturated fatty acids (PUFAs) in patients with autism is associated with the expression of related liver metabolic enzymes, we selected rats that were exposed to valproic acid (VPA) on embryonic day 12.5 (E12.5) as a model of autism. We observed the serum levels of PUFAs and the expression of related liver metabolic enzymes, including Δ5-desaturase, Δ6-desaturase and elongase (Elovl2), in VPA-exposed and control rats on postnatal day 35 (PND35) and conducted sex dimorphic analysis. We found that the levels of serum PUFAs and related liver metabolic enzymes in the VPA rats were significantly reduced, in association with autism-like behavioral changes, the abnormal expression of apoptosis-related proteins and hippocampal neuronal injury, compared to the control rats and showed sex difference in VPA group. This finding indicated that rats exposed to VPA at the embryonic stage may exhibit reduced synthesis of serum PUFAs due to the down-regulation of liver metabolic enzymes, thereby inducing nervous system injury and behavioral changes, which is affected by sex in the meantime.
为了研究自闭症患者血清多不饱和脂肪酸(PUFAs)水平降低是否与相关肝脏代谢酶的表达有关,我们选择在胚胎第12.5天(E12.5)暴露于丙戊酸(VPA)的大鼠作为自闭症模型。我们观察了出生后第35天(PND35)时VPA暴露组和对照组大鼠血清PUFAs水平以及相关肝脏代谢酶的表达,包括Δ5-去饱和酶、Δ6-去饱和酶和延长酶(Elovl2),并进行了性别差异分析。我们发现,与对照组大鼠相比,VPA大鼠的血清PUFAs水平和相关肝脏代谢酶显著降低,伴有自闭症样行为改变、凋亡相关蛋白的异常表达和海马神经元损伤,且VPA组存在性别差异。这一发现表明,胚胎期暴露于VPA的大鼠可能由于肝脏代谢酶的下调而导致血清PUFAs合成减少,从而引起神经系统损伤和行为改变,同时受到性别的影响。