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海马体中FGF-2和FGFR1 mRNA在重度抑郁症、精神分裂症和双相情感障碍中的表达

Hippocampal FGF-2 and FGFR1 mRNA expression in major depression, schizophrenia and bipolar disorder.

作者信息

Gaughran Fiona, Payne Joachim, Sedgwick Philip M, Cotter David, Berry Martin

机构信息

Institute of Psychiatry, De Crespigny Park, London SE5 8AF, United Kingdom.

出版信息

Brain Res Bull. 2006 Jul 31;70(3):221-7. doi: 10.1016/j.brainresbull.2006.04.008. Epub 2006 May 12.

Abstract

INTRODUCTION

FGF-2 is important for stem cell proliferation, neocortical development and adult neuronal survival and growth. Reduced frontal cortical FGF-2 expression is described in major depression and is attenuated by antidepressants. We determined the distribution of hippocampal FGF-2 and its receptor (FGFR1) mRNA in post-mortem brains of people who suffered from major depression, bipolar disorder and schizophrenia and those of controls.

METHODS

FGF-2 and FGFR1 mRNA were measured within hippocampal CA1, CA4 regions and the dentate gyrus (DG), using in situ hybridization. Within hippocampal regions, cellular staining was compared between diagnostic groups, using repeated measures analysis of variance.

RESULTS

The density of FGF-2 mRNA+ cells in CA4 was reduced in depression compared to controls. The percentage of FGFR1 mRNA+ cells was higher in depression (CA1 and CA4) and schizophrenia (CA4) than in controls. FGFR1 mRNA expression was higher in depression than in the other groups in CA1, CA4 and DG. Overall FGF-2 mRNA expression was higher in DG than in CA1 and CA4.

CONCLUSIONS

We found raised measures of FGFR1 mRNA+ in major depression and, less so, in schizophrenia, along with reduced FGF-2 mRNA density in depression. Perturbations of FGF regulation could be relevant to the pathogenesis of both disorders as FGF-2 and FGFR1 are implicated in normal hippocampal synaptology, stem cell recruitment, and connectivity, and are modulated by corticosteroids.

摘要

引言

成纤维细胞生长因子2(FGF - 2)对干细胞增殖、新皮质发育以及成年神经元的存活和生长至关重要。在重度抑郁症中,额叶皮质FGF - 2表达降低,且抗抑郁药可使其减弱。我们测定了重度抑郁症、双相情感障碍和精神分裂症患者以及对照组死后大脑中海马体FGF - 2及其受体(FGFR1)mRNA的分布。

方法

采用原位杂交技术测定海马体CA1、CA4区域及齿状回(DG)内的FGF - 2和FGFR1 mRNA。在海马体区域内,使用重复测量方差分析比较诊断组之间的细胞染色情况。

结果

与对照组相比,抑郁症患者CA4区域中FGF - 2 mRNA +细胞的密度降低。抑郁症(CA1和CA4)和精神分裂症(CA4)患者中FGFR1 mRNA +细胞的百分比高于对照组。在CA1、CA4和DG区域,抑郁症患者的FGFR1 mRNA表达高于其他组。总体而言,DG区域的FGF - 2 mRNA表达高于CA1和CA4区域。

结论

我们发现重度抑郁症患者以及精神分裂症患者(程度较轻)中FGFR1 mRNA +水平升高,同时抑郁症患者的FGF - 2 mRNA密度降低。FGF调节的紊乱可能与这两种疾病的发病机制相关,因为FGF - 2和FGFR1参与正常海马体突触形成、干细胞募集和连接,并受皮质类固醇调节。

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