Nishi M, Whitaker-Azmitia P M, Azmitia E C
Department of Biology, New York University, New York 10003, USA.
Synapse. 1996 May;23(1):1-9. doi: 10.1002/(SICI)1098-2396(199605)23:1<1::AID-SYN1>3.0.CO;2-E.
Serotonin (5-HT) has been shown to modulate brain maturation during development and adult plasticity. This effect in the whole animal may be due to activation of 5-HT1A receptors and a corresponding increases in S100b and corticosterone. Synaptophysin, an integral protein of the synaptic vesicle membrane that correlates with synaptic density and neurotransmitter release, is reduced by depletion of 5-HT in the cortex and hippocampus of the adult rat. Injections of a 5-HT1A agonist or dexamethasone can reverse the loss of synaptophysin immunoreactivity (IR). In this study we used morphometric analysis of synaptophysin-IR to study the effects of the 5-HT1A agonist, ipsapirone, and the neuronal extension factor, S100b on hippocampal neurons grown in a serum and steroid free media. Both compounds increased the synaptophysin-IR at doses previously established to be highly specific. Ipsapirone (10(-9)M) was more effective on neuronal cell bodies staining and S100b (10 ng/ml) was more effective in increasing the number of synaptophysin-IR varicosities on neuronal processes. In addition both types of corticosteroid receptor agonists, at previously established specific doses, Ru28362 (10(-8) M) and aldosterone (10(-9) M) produced smaller increases compared to control groups in both the cell body staining and the number of varicosities. The effect of these differentiating factors on the expression of synaptophysin-IR suggests multiple regulation sites for producing and maintaining pre-synaptic elements in the brain.
血清素(5-羟色胺,5-HT)已被证明在发育过程中调节大脑成熟以及在成体可塑性方面发挥作用。在整个动物体内,这种作用可能归因于5-HT1A受体的激活以及S100b和皮质酮相应的增加。突触素是突触囊泡膜的一种整合蛋白,与突触密度和神经递质释放相关,成年大鼠皮质和海马中5-HT的耗竭会使其减少。注射5-HT1A激动剂或地塞米松可逆转突触素免疫反应性(IR)的丧失。在本研究中,我们使用突触素-IR的形态计量分析来研究5-HT1A激动剂伊沙匹隆和神经元延伸因子S100b对在无血清和无类固醇培养基中生长的海马神经元的影响。两种化合物在先前确定的高特异性剂量下均增加了突触素-IR。伊沙匹隆(10⁻⁹M)对神经元细胞体染色更有效,而S100b(10 ng/ml)在增加神经元突起上突触素-IR曲张体数量方面更有效。此外,两种类型的皮质类固醇受体激动剂,在先前确定的特定剂量下,RU28362(10⁻⁸M)和醛固酮(10⁻⁹M)与对照组相比,在细胞体染色和曲张体数量方面产生的增加较小。这些分化因子对突触素-IR表达的影响表明,在大脑中产生和维持突触前元件存在多个调节位点。