N-methyl-N-nitrosourea-induced cerebellar hypoplasia in rats: Effect of arachidonic acid supplementation during the gestational, lactational and post-weaning periods.

N-methyl-N-nitrosourea-induced cerebellar hypoplasia in rats: Effect of arachidonic acid supplementation during the gestational, lactational and post-weaning periods.
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DOI:
10.3892/etm.2013.1219
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发表时间:
2013-09
影响因子:
2.7
通讯作者:
Tsubura A
Tsubura A
中科院分区:
医学4区
文献类型:
--
作者:
Yoshizawa K;Emoto Y;Kinoshita Y;Yuri T;Tsubura A

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花生四烯酸(AA)是一种对视觉和大脑发育很重要的脂肪酸,通常作为功能性食品成分添加到世界各地的商业婴儿配方奶粉中。然而,很少有研究检验新生儿期间补充AA是否对神经元异常有影响。本研究通过检测N-甲基-N-亚硝脲(MNU)诱导的幼年Lewis大鼠小脑发育不良,研究了妊娠和哺乳期饲喂AA对母鼠的影响。母猪饲喂2.0%AA日粮或基础日粮(0.01%AA)。出生时(出生后第0天),雄性和雌性幼鼠单次腹腔注射35 mg/kg MNU或赋形剂。分别于术后7、14、21、28、60天称量脑重量,并对大体标本和组织学标本进行形态分析。无论大鼠是否喂食AA饮食,从注射MNU后第14天开始,MNU处理的大鼠的脑重,特别是小脑的重量,与未处理MNU的大鼠相比都有所下降。在MNU处理的大鼠中,也检测到小脑长度和/或宽度的宏观减少以及组织学观察到的小脑顶高度和/或皮质宽度的减少,无论这些大鼠是否喂食了AA。在组织病理学上,MNU处理的大鼠(与补充AA无关)表现出小脑皮质的紊乱和皮质层的紊乱(分子层、浦肯野细胞层和颗粒细胞层的丢失和/或紊乱)。MNU处理的大鼠之间的任何参数都没有显著差异,无论这些大鼠是否喂食了AA饮食。总而言之,在妊娠和哺乳期为母鼠提供富含AA的饮食并不能改变MNU诱导的子代小脑发育不良。
Arachidonic acid (AA) is a fatty acid that is important for visual and brain development and is commonly added as a functional food ingredient to commercial infant formulas worldwide. However, few studies have examined whether AA supplementation during neonatal life has an effect on neuronal abnormalities. In the present study, the effect of dietary AA supplementation in dams during gestation and lactation was investigated by examining N-methyl-N-nitrosourea (MNU)-induced cerebellar hypoplasia in young Lewis rats. Dams were fed a 2.0% AA diet or a basal diet (<0.01% AA). At birth (postnatal day 0), male and female pups received a single intraperitoneal injection of 35 mg/kg MNU or vehicle. Brain weights were measured and a morphological analysis of macroscopic and histological specimens was conducted after 7, 14, 21, 28 and 60 days. Irrespective of whether the rats had been fed an AA diet, the brain weights of the MNU-treated rats, particularly the weights of the cerebellum, were decreased compared with those of the MNU-untreated rats from the 14th day following the MNU injection. Macroscopic reductions in the cerebellar length and/or width and histologically observed reductions in cerebellar vertex height and/or cortex width were also detected in the MNU-treated rats, irrespective of whether the rats had been fed with AA. Histopathologically, the MNU-treated rats (irrespective of AA supplementation) exhibited disorganization of the cerebellar cortex and disarrangement of the cortical layers (loss and/or disturbance of the molecular, Purkinje and granular cell layers). There were no significant differences in any parameters among the MNU-treated rats, irrespective of whether the rats had been fed an AA diet. In conclusion, an AA-rich diet for dams during gestation and lactation did not modify MNU-induced cerebellar hypoplasia in their offspring.
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