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  • Deficits in LTP induction by 5-HT2A receptor antagonist in a mouse model for fragile X syndrome.

Deficits in LTP induction by 5-HT2A receptor antagonist in a mouse model for fragile X syndrome.

PloS one (2012-11-03)
Zhao-hui Xu, Qi Yang, Lan Ma, Shui-bing Liu, Guang-sheng Chen, Yu-mei Wu, Xiao-qiang Li, Gang Liu, Ming-gao Zhao
摘要

Fragile X syndrome is a common inherited form of mental retardation caused by the lack of fragile X mental retardation protein (FMRP) because of Fmr1 gene silencing. Serotonin (5-HT) is significantly increased in the null mutants of Drosophila Fmr1, and elevated 5-HT brain levels result in cognitive and behavioral deficits in human patients. The serotonin type 2A receptor (5-HT2AR) is highly expressed in the cerebral cortex; it acts on pyramidal cells and GABAergic interneurons to modulate cortical functions. 5-HT2AR and FMRP both regulate synaptic plasticity. Therefore, the lack of FMRP may affect serotoninergic activity. In this study, we determined the involvement of FMRP in the 5-HT modulation of synaptic potentiation with the use of primary cortical neuron culture and brain slice recording. Pharmacological inhibition of 5-HT2AR by R-96544 or ketanserin facilitated long-term potentiation (LTP) in the anterior cingulate cortex (ACC) of WT mice. The prefrontal LTP induction was dependent on the activation of NMDARs and elevation of postsynaptic Ca(2+) concentrations. By contrast, inhibition of 5-HT2AR could not restore the induction of LTP in the ACC of Fmr1 knock-out mice. Furthermore, 5-HT2AR inhibition induced AMPA receptor GluR1 subtype surface insertion in the cultured ACC neurons of Fmr1 WT mice, however, GluR1 surface insertion by inhibition of 5-HT2AR was impaired in the neurons of Fmr1KO mice. These findings suggested that FMRP was involved in serotonin receptor signaling and contributed in GluR1 surface expression induced by 5-HT2AR inactivation.

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Sigma-Aldrich
单克隆抗 β-肌动蛋白抗体 小鼠抗, clone AC-74, ascites fluid
Sigma-Aldrich
抗-NMDAR2A抗体, Chemicon®, from mouse
Sigma-Aldrich
Anti-NMDAR2B Antibody, ascites fluid, clone 1E4.25A4, Chemicon®