Alterations of central noradrenergic transmission in Ts65Dn mouse, a model for Down syndrome
Alterations of central noradrenergic transmission in Ts65Dn mouse, a model for Down syndrome
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DOI：
10.1016/s0006-8993(96)01173-0
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发表时间：
1997-02-28
期刊：
影响因子：
2.9
通讯作者：
Florez, J
中科院分区：
文献类型：
--
作者：
Dierssen, M;Vallina, IF;Florez, J
将具有节段性16三体（Ts65Dn）的小鼠用作唐氏综合征的模型，所述小鼠具有与人染色体21中的唐氏综合征关键区域同源的小鼠染色体16的区域的三重化。在Ts65Dn小鼠中研究了中枢β-去甲肾上腺素能传递的功能。大脑皮层中的结合分析显示β-肾上腺素受体的数量没有变化，亲和力略有降低。通过分析在基础条件下和用异丙肾上腺素和毛喉素刺激后大脑皮质、海马和小脑皮质中的cAMP形成来评估β-肾上腺素受体转导。与对照组相比，Ts65Dn小鼠海马和小脑皮质cAMP的基础产生显著减少，但小脑中没有。磷酸二酯酶抑制后，两组小鼠cAMP积累的净增量相似，异丙肾上腺素（10 μ M）和毛喉素（10 μ M）对海马cAMP产生的刺激远高于两组的大脑皮质。在这两个领域，但不是在小脑，刺激反应是一致的，并显着小于在对照组小鼠Ts65Dn。异丙肾上腺素和毛喉素的浓度-反应曲线，在大脑皮层中产生。E（最大）的反应是较低的三体比对照组小鼠，然而，在Ts65Dn小鼠的反应曲线的斜率异丙肾上腺素显着抑制，而毛喉素是类似的控制。它的结论是，Ts65Dn小鼠表现出七个缺陷的中枢β-去甲肾上腺素能系统，这是选择性的特定脑区的突触传递。(C)1997年Elsevier Science B.V.
Mice with segmental trisomy 16 (Ts65Dn) which have triplication of a region of mouse chromosome 16 homologous to the Down syndrome critical region in human chromosome 21, are used as a model for Down syndrome. Functioning of the central beta-noradrenergic transmission was studied in Ts65Dn mice. Binding analysis in cerebral cortex revealed no change in the number of beta-adrenoceptors and a slight reduction of affinity. The beta-adrenoceptor transduction was assessed by analyzing cAMP formation in the cerebral cortex, hippocampus and cerebellar cortex under basal conditions and after stimulation with isoprenaline and forskolin. Basal production of cAMP was significantly reduced in hippocampus and cerebellar cortex of Ts65Dn mice compared to control, but not in cerebellum. After phosphodiesterase inhibition, net increments in cAMP accumulation were similar in both groups of mice, Stimulation of cAMP production by isoprenaline (10 mu M) and forskolin (10 mu M) was much higher in hippocampus than in cerebral cortex of either group. In both areas, but not in cerebellum, the stimulatory responses were consistently and significantly smaller in Ts65Dn than in control mice. Concentration-response curves for isoprenaline and forskolin were, generated in the cerebral cortex. E(max) responses were lower in trisomic than in control mice; however, in Ts65Dn mice the slope of the response curve to isoprenaline was markedly depressed whereas that to forskolin was similar to control. It is concluded that Ts65Dn mice show seven deficiencies in the synaptic transmission of the central beta-noradrenergic system, which are selective for specific brain areas. (C) 1997 Elsevier Science B.V.