The effect of hyperphenylalaninemia on size and density of synapses in rat neocortex
The effect of hyperphenylalaninemia on size and density of synapses in rat neocortex
复制标题
高苯丙氨酸血症对大鼠新皮质突触大小和密度的影响
DOI：
10.1016/0006-8993(79)90507-9
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发表时间：
1979
期刊：
影响因子：
2.9
通讯作者：
D. Labar
中科院分区：
文献类型：
--
作者：
M. Nigam;D. Labar
修改在突触组成的大脑皮层的年轻哺乳动物已被发现后，几种实验manipulationZ，4，6-S，13。尽管Golgi研究表明这种变化发生在具有特定精神发育迟滞综合征的人类或动物的大脑中，但关于这种变化的信息很少2，6，10，14- 16。在出生后发育期间暴露于高水平苯丙氨酸的大鼠具有持久的行为缺陷1，因此被用作人类苯丙酮尿症的模型。在这项研究中，我们应用定量电子显微镜方法，以确定治疗的影响，对突触末梢的数量，大小和分布的高苯丙氨酸血症大鼠的大脑皮层。四只Sprague-Dawley、白化病大鼠在出生后的前21天内每天接受两次L-苯丙氨酸治疗，1000 mg/kg，每天两次（n= 2）或每天一次联合使用400 mg/kg L-苯丙氨酸和DL-α-甲基苯丙氨酸（n-2）。后者已显示出抑制苯丙氨酸羟化酶9的活性。用等体积的稀释游离胺II（McGaw）处理3份对照品。通过使用Beckman氨基酸分析仪17的快速分析，在相同处理的动物系列中测量血清苯丙氨酸水平。在第21天用混合醛固定剂11灌注动物。将脑称重，在距额极尖端5 mm处冠状切片成1 mm厚的切片，并根据常规技术处理用于电子显微镜检查的块，并包埋在Epon中。手动切割，10-20 μ m，染色切片，垂直于软脑膜表面切割，证实组织来自Krieg 12的区域2。将银干扰薄切片（约0.06/μ m）固定在平行杆网格上，以允许对整个皮质深度进行不间断检查，用醋酸双氧铀和柠檬酸铅进行双重染色。所有数据均来自20 m宽的皮质条的摄影蒙太奇。我们通过突触小泡和突触后特化的存在来鉴定突触末梢。照片的放大倍数是12500。对所有终末进行计数，并与Fifkova关于光剥夺后突触变化的研究5相同，突触后特化的长度为
Modification in the synaptic composition of the cerebral cortex of young mammals has been found after several kinds of experimental manipulationsZ, 4, 6-s, 13. There is little information about similar changes in brains of humans or animals with specific mental retardation syndromes although Golgi studies suggest that such changes occur 2, 6, 10, 14-16.Rats exposed to high levels of phenylalanine during postnatal development have enduring behavioral deficits 1 and thus have been used as models for human phenylketonuria. In this study we have applied quantitative electron microscopic methods to the cerebral cortex of hyperphenylalaninemic rats to define the effects of treatment on the numbers, sizes and distribution of synaptic terminals. Four Sprague-Dawley, albino rats were treated twice daily for the first 21 days of life with either L-phenylalanine, 1000 mg/kg twice daily (n= 2) or once daily with a combination of 400 mg/kg each of L-phenylalanine and DL-alpha-methyl phenylalanine (n----2). The latter has been shown to inhibit the activity of phenylalanine hydroxylase 9. Three controls were treated with equivalent volumes of diluted Free-Amine II,(McGaw). Serum phenylalanine levels were measured in identically treated series of animals by rapid analysis using the Beckman amino acid analyzer 17. The animals were perfused on day 21 with a mixed aldehyde fixative 11. The brains were weighed, sectioned coronally into 1 mm thick slices 5 mm from the tip of the frontal pole and blocks processed for electron microscopy according to conventional techniques and embedded in Epon. Hand cut, 10-20/~ m, stained sections, cut perpendicular to the pial surface confirmed that the tissue was from area 2 of Krieg 12. Thin sections of silver interference (approximately 0.06/~ m) mounted on parallel bar grids to allow uninterrupted examination of the entire depth of cortex, were doublestained with uranyl acetate and lead citrate. All data was collected from photographic montages from a 20~ m wide strip of cortex. We identified synaptic terminals by the presence of synaptic vesicles and post-synaptic specialization. The magnification of the pictures was 12,500. All terminals were counted and as in Fifkova's study 5 of synaptic changes after light deprivation, the length of the post-synaptic specialization was