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大鼠上丘中γ-氨基丁酸(GABA)受体谱的产后变化

Postnatal alterations of GABA receptor profiles in the rat superior colliculus.

作者信息

Clark S E, Garret M, Platt B

机构信息

Department of Biomedical Sciences, Aberdeen University, Foresterhill, AB25 2ZD, Aberdeen, UK.

出版信息

Neuroscience. 2001;104(2):441-54. doi: 10.1016/s0306-4522(01)00087-2.

Abstract

Midbrain sections taken from Sprague-Dawley rats of varying ages within the first four postnatal weeks were used to determine, immunocytochemically, putative changes of GABA(A) receptor beta2/3 subunits, GABA(B) receptor (R1a and R1b splice variants), and GABA(C) receptor rho1 subunit expression and distribution in the superficial, visual layers of the superior colliculus. Immunoreactivity for the GABA(A) receptor beta2/3 subunits was found in the superficial grey layer from birth. The labelling changed with age, with an overall continuous reduction in the number of cells labelled and a significant increase in the labelling intensity distribution (neuropil vs soma). Further analysis revealed an initial increase in the labelling intensity between postnatal days 0 and 7 in parallel with an overall reduction of labelled neurones. This was followed by a significant decrease in labelling intensity distribution between postnatal days 7 and 16, and a subsequent increase in intensity between postnatal days 16 and 28. The labelling profiles for GABA(B) receptors (R1a and R1b splice variants) and GABA(C) receptors (rho1 subunit) showed similar patterns. Both receptors could be found in the superficial layers of the superior colliculus from birth, and the intensity and distribution of labelling remained constant during the first postnatal month. However, the cell body count showed a significant decrease between postnatal days 7 and 16. These changes may be related to the time-point of eye opening, which occurred approximately two weeks after birth. For all three receptor types, the cell body count remained constant after postnatal day 16. By four weeks of age, there was no significant difference between the cell numbers obtained for the different receptors. Both GABA itself and neurofilament labelling were also obtained in the superficial superior colliculus at birth. Neurofilament, although found at birth, showed very little ordered arrangement until 16days after birth. When slices were double labelled for GABA(C) receptors and neurofilament, some overlap was observed. Double labelling for the presynaptic protein synaptophysin and GABA(C) receptors showed proximity in some places, indicative of a partly synaptic location of GABA(C) receptors. When GABA(C) and GABA(A) receptors were labelled simultaneously, some but not all neurones showed immunoreactivity for both receptor types. In conclusion, all three GABA receptor types were found to be present in the superior colliculus from birth, and all show some form of postnatal modification, with GABA(A) receptors demonstrating the most dramatic changes. However, GABA(B) and GABA(C) receptors are modified significantly around the onset of input-specific activity. Together, this points towards a contribution of the GABAergic system to processes of postnatal maturation in the superficial superior colliculus.

摘要

取自出生后前四周内不同年龄的Sprague-Dawley大鼠的中脑切片,用于免疫细胞化学测定上丘视觉表层中GABA(A)受体β2/3亚基、GABA(B)受体(R1a和R1b剪接变体)以及GABA(C)受体rho1亚基表达和分布的假定变化。从出生起就在上丘的浅灰质层发现了GABA(A)受体β2/3亚基的免疫反应性。标记随年龄变化,标记细胞数量总体持续减少,标记强度分布(神经毡与胞体)显著增加。进一步分析显示,出生后0至7天标记强度最初增加,同时标记神经元总数减少。随后,出生后7至16天标记强度分布显著下降,出生后16至28天强度又增加。GABA(B)受体(R1a和R1b剪接变体)和GABA(C)受体(rho1亚基)的标记模式相似。两种受体从出生起就可在上丘表层发现,出生后第一个月内标记强度和分布保持不变。然而,胞体计数在出生后7至16天显著减少。这些变化可能与出生后约两周出现的睁眼时间点有关。对于所有三种受体类型,出生后16天胞体计数保持不变。到四周龄时,不同受体的细胞数量之间无显著差异。出生时在上丘表层也获得了GABA本身和神经丝标记。神经丝虽然在出生时就有,但直到出生后16天才显示出很少的有序排列。当切片对GABA(C)受体和神经丝进行双重标记时,观察到一些重叠。对突触前蛋白突触素和GABA(C)受体进行双重标记时,在某些部位显示出接近,表明GABA(C)受体部分位于突触处。当同时标记GABA(C)和GABA(A)受体时,部分而非所有神经元对两种受体类型均显示免疫反应性。总之,发现所有三种GABA受体类型从出生起就存在于上丘中,且均显示出某种形式的出生后修饰,其中GABA(A)受体变化最为显著。然而,GABA(B)和GABA(C)受体在输入特异性活动开始时发生显著修饰。总体而言,这表明GABA能系统对上丘表层出生后成熟过程有贡献。

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