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Existence of FGFR1-5-HT1AR heteroreceptor complexes in hippocampal astrocytes. Putative link to 5-HT and FGF2 modulation of hippocampal gamma oscillations.
Neuropharmacology ( IF 4.7 ) Pub Date : 2020-03-27 , DOI: 10.1016/j.neuropharm.2020.108070
Manuel Narváez 1 , Yuniesky Andrade-Talavera 2 , Ismael Valladolid-Acebes 3 , Magnus Fredriksson 4 , Pia Siegele 4 , Alejandro Hernandez-Sosa 4 , André Fisahn 2 , Kjell Fuxe 4 , Dasiel O Borroto-Escuela 5
Affiliation  

The majority of the fibroblast growth factor receptor 1-serotonin 1 A receptor (FGFR1-5-HT1AR) heterocomplexes in the hippocampus appeared to be located mainly in the neuronal networks and a relevant target for antidepressant drugs. Through a neurochemical and electrophysiological analysis it was therefore tested in the current study if astrocytic FGFR1-5-HT1AR heterocomplexes also exist in hippocampus. They may modulate the structure and function of astroglia in the hippocampus leading to possible changes in the gamma oscillations. Localization of hippocampal FGFR1-5-HT1AR heterocomplexes in astrocytes was found using in situ proximity ligation assay combined with immunohistochemistry using glial fibrillary acidic protein (GFAP) immunoreactivity as a marker for astroglia. Acute i.c.v. treatment with 8-OH-DPAT alone or together with basic fibroblast growth factor (FGF2) significantly increased FGFR1-5-HT1AR heterocomplexes in the GFAP positive cells, especially in the polymorphic layer of the dentate gyrus (PoDG) but also in the CA3 area upon combined treatment. No other hippocampal regions were studied. Also, structural plasticity changes were observed in the astrocytes, especially in the PoDG region, upon these pharmacological treatments. They may also be of relevance for enhancing the astroglial volume transmission with increased modulation of the neuronal networks in the regions studied. The effects of combined FGF2 and 5-HT agonist treatments on gamma oscillations point to a significant antagonistic interaction in astroglial FGFR1-5-HT1AR heterocomplexes that may contribute to counteraction of the 5-HT1AR-mediated decrease of gamma oscillations. This article is part of the special issue entitled 'Serotonin Research: Crossing Scales and Boundaries'.

中文翻译:

海马星形胶质细胞中存在FGFR1-5-HT1AR异源受体复合物。推测与海马γ振荡的5-HT和FGF2调节有关。

海马中的大多数成纤维细胞生长因子受体1-血清素1A受体(FGFR1-5-HT1AR)杂合物似乎主要位于神经元网络中,并且是抗抑郁药的相关靶标。通过神经化学和电生理学分析,因此在本研究中测试了海马中是否还存在星形细胞FGFR1-5-HT1AR杂合物。它们可能会调节海马中星形胶质细胞的结构和功能,从而导致伽玛振动的可能变化。使用胶质纤维酸性蛋白(GFAP)免疫反应性作为星形胶质细胞的标记物,采用原位邻近结扎法结合免疫组织化学方法,发现星形胶质细胞中海马FGFR1-5-HT1AR杂合物的定位。急性ICV 单独使用8-OH-DPAT或与碱性成纤维细胞生长因子(FGF2)一起治疗,可显着增加GFAP阳性细胞中FGFR1-5-HT1AR异源复合物,特别是在齿状回(PoDG)的多态层以及CA3区域经过综合治疗。没有研究其他海马区。同样,在这些药理学处理后,在星形胶质细胞中观察到结构可塑性变化,特别是在PoDG区域。它们也可能与增加研究区域神经元网络的调节来增强星形胶质细胞的体积传递有关。FGF2和5-HT激动剂联合治疗对伽马振荡的影响表明,星形胶质FGFR1-5-HT1AR杂合物中存在明显的拮抗作用,这可能有助于抵消5-HT1AR介导的伽马振荡减少。本文是名为“ 5-羟色胺研究:交叉标度和边界”的特刊的一部分。
更新日期:2020-03-27
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