Pharmacological rescue of synaptic plasticity, courtship behavior, and mushroom body defects in a Drosophila model of fragile X syndrome
Pharmacological rescue of synaptic plasticity, courtship behavior, and mushroom body defects in a Drosophila model of fragile X syndrome
复制标题
DOI：
10.1016/j.neuron.2005.01.038
复制
发表时间：
2005-03-03
期刊：
影响因子：
16.2
通讯作者：
Jongens, TA
中科院分区：
文献类型：
--
作者：
McBride, SMJ;Choi, CH;Jongens, TA
脆性X染色体综合征是一种主要的遗传性精神发育迟滞的原因，导致FMR 1基因功能的丧失。基于dfmr1活性丧失的果蝇脆性X综合征模型，表现出与脆性X相关症状相似的表型。在此，我们证明了用代谢型谷氨酸受体（mGluR）拮抗剂或锂治疗可以挽救在这些苍蝇中观察到的求爱和蘑菇体缺陷。此外，我们表明，dfmr1突变体显示认知缺陷的经验依赖性修改的求爱行为，和治疗mGluR拮抗剂或锂恢复这些记忆缺陷。这些发现暗示增强的mGluR信号传导是在果蝇脆性X模型中观察到的认知以及一些行为和神经元表型的根本原因。他们还提出了一种可能性，即对代谢型谷氨酸受体具有类似作用的化合物可以改善脆性X患者中观察到的认知和行为缺陷。
Fragile X syndrome is a leading heritable cause of mental retardation that results from the loss of FMR1 gene function. A Drosophila model for Fragile X syndrome, based on the loss of dfmr1 activity, exhibits phenotypes that bear similarity to Fragile X-related symptoms. Herein, we demonstrate that treatment with metabotropic glutamate receptor (mGluR) antagonists or lithium can rescue courtship and mushroom body defects observed in these flies. Furthermore, we demonstrate that dfmr1 mutants display cognitive deficits in experience-dependent modification of courtship behavior, and treatment with mGluR antagonists or lithium restores these memory defects. These findings implicate enhanced mGluR signaling as the underlying cause of the cognitive, as well as some of the behavioral and neuronal, phenotypes observed in the Drosophila Fragile X model. They also raise the possibility that compounds having similar effects on metabotropic glutamate receptors may ameliorate cognitive and behavioral defects observed in Fragile X patients.