代谢型谷氨酸受体 7 作为 MECP2 重复综合征的新治疗靶点-猫眼课题宝

代谢型谷氨酸受体 7 作为 MECP2 重复综合征的新治疗靶点

批准号：

9466186

负责人：

Nicole Marie Fisher

金额：

$2.87万

依托单位：

VANDERBILT UNIVERSITY

依托单位国家：

美国

项目类别：

财政年份：

2017

资助国家：

美国

项目状态：

已结题

起止时间：

2017-09-30 至 2020-09-29

来源：

https://reporter.nih.gov/project-details/9466186

关键词：

Affect Age Animals Apnea Autopsy Back Behavior Brain Brain region Cerebellum Chemosensitization Child Cognition Cognitive Corpus striatum structure Data Diagnosis Disease Electrophysiology (science)Excitatory Postsynaptic Potentials Exhibits Extinction (Psychology)Female Freezing Fright G-Protein-Coupled Receptors GTP-Binding Protein alpha Subunits, Gs Gene Dosage Gene Expression Genes Glutamates Hippocampus (Brain)Impairment In Vitro Intellectual functioning disability Lead Learning Long-Term Potentiation Memory Memory impairment Methyl-CpG-Binding Protein 2 Modeling Mus Neurobehavioral Manifestations Neurodevelopmental Disorder Neurologic Neurons Patients Pharmacological Treatment Pharmacology Phenotype Presynaptic Terminals Receptor Activation Reporting Research Proposals Rett Syndrome Reversal Learning Role Sampling Seizures Slice Speech Synapses Synaptic plasticity Syndrome Testing Therapeutic Translating Western Blotting behavior test conditioned fear fear memory hippocampal pyramidal neuron insight learned behavior loss of function loss of function mutation metabotropic glutamate receptor 7 morris water maze motor control motor impairment mouse model nervous system disorder neurophysiology neurotransmitter release new therapeutic target novel therapeutic intervention overexpression positive allosteric modulator postsynaptic protein expression receptor respiratory response skills spatial memory tool transcription factor

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英文摘要

PROJECT SUMMARY Loss-of-function mutation of the Methyl CpG Binding Protein 2 (MECP2) gene causes a severe neurodevelopmental disorder known as Rett syndrome (RTT), while duplication of its locus leads to MECP2 Duplication syndrome (MDS). Children with each diagnosis can present with profound intellectual disability for which there is currently no treatment. Here we provide preliminary data showing that expression of the metabotropic glutamate receptor 7 (mGlu7), a receptor with known roles in synaptic plasticity and cognition, is altered downstream of changes in MECP2 gene dosage. While potentiation of mGlu7 activity ameliorates phenotypes in RTT mice, the therapeutic potential of mGlu7 modulation in a model of MDS remains unexplored. Completion of this research proposal will thoroughly investigate the efficacy of mGlu7 modulation in paradigms of learning and memory in a mouse model of MDS and provide new mechanistic insight into the neurophysiological role of mGlu7 in the context of MeCP2-related disorders.

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