Fragile X Syndrome (FXS) is the most common form of inherited intellectual disability and a leading genetic cause of autism, frequently associated with epilepsy and abnormal behavior. Studies on animal models have revealed that FXS involves abnormal synaptic transmission and plasticity in several brain areas. Serotonin 5-HT7 receptors are expressed in brain structures involved in learning and memory and modulate neuronal excitability as well as glutamatemediated synaptic transmission. We have recently shown that activation of 5-HT7 receptors reversed metabotropic glutamate receptormediated long-term depression (mGluR-LTD) in wildtype and in Fmr1 KO mice (Costa et al., 2012), a mouse model of Fragile X syndrome (FXS) in which mGluR-LTD is pathologically enhanced (Huber et al., 2002), suggesting that 5-HT7 receptor agonists might be envisaged as a novel therapeutic strategy for FXS. In Fmr1 KO mice, enhanced mGluR-LTD is an electrophysiological readout of exaggerated signalling through group I mGluRs, leading to excessive protein synthesis and malfunction of several downstream targets (Bhakar et al., 2012). Our current hypothesis is that activation of 5-HT7 receptors might correct abnormal phenotypes of FXS by reducing mGluRmediated signaling.

ACTIVATION OF SEROTONIN TYPE 7 (5-HT7) RECEPTORS AS A NOVEL THERAPEUTIC STRATEGY IN FRAGILE X SYNDROME UNA NUOVA STRATEGIA TERAPEUTICA PER LA SINDROME DEL CROMOSOMA X FRAGILE BASATA SU NUOVE MOLECOLE ATTIVANTI I RECETTORI 5-HT7 PER LA SEROTONINA

COSTA, LARA TANIA;
2015-01-01

Abstract

Fragile X Syndrome (FXS) is the most common form of inherited intellectual disability and a leading genetic cause of autism, frequently associated with epilepsy and abnormal behavior. Studies on animal models have revealed that FXS involves abnormal synaptic transmission and plasticity in several brain areas. Serotonin 5-HT7 receptors are expressed in brain structures involved in learning and memory and modulate neuronal excitability as well as glutamatemediated synaptic transmission. We have recently shown that activation of 5-HT7 receptors reversed metabotropic glutamate receptormediated long-term depression (mGluR-LTD) in wildtype and in Fmr1 KO mice (Costa et al., 2012), a mouse model of Fragile X syndrome (FXS) in which mGluR-LTD is pathologically enhanced (Huber et al., 2002), suggesting that 5-HT7 receptor agonists might be envisaged as a novel therapeutic strategy for FXS. In Fmr1 KO mice, enhanced mGluR-LTD is an electrophysiological readout of exaggerated signalling through group I mGluRs, leading to excessive protein synthesis and malfunction of several downstream targets (Bhakar et al., 2012). Our current hypothesis is that activation of 5-HT7 receptors might correct abnormal phenotypes of FXS by reducing mGluRmediated signaling.
2015
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11570/3059778
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