Hippocampal dysregulation of FMRP/mGluR5 signaling in engrailed-2 knockout mice: a model of autism spectrum disorders. Issue 18 (16th December 2015)

• Record Type: Journal Article
• Authors: Provenzano, Giovanni; Sgadò, Paola; Genovesi, Sacha; Zunino, Giulia; Casarosa, Simona; Bozzi, Yuri
• Is Part Of: NeuroReport. Volume 26:Issue 18(2015)
• Publication Date: 2015-12-16
• Subjects: autism -- engrailed -- fragile X -- GABA -- glutamate -- hippocampus -- neurodevelopmental disorder; Neurosciences -- Periodicals; Nervous system -- Periodicals; Neurophysiology -- Periodicals; Nervous System Diseases -- Periodicals; Nervous System Physiological Phenomena -- Periodicals; Neurosciences -- Periodicals; 616.805
• DOI: 10.1097/WNR.0000000000000477
• Languages: English
• ISSNs: 0959-4965

Abstract

Abstract : Many evidences indicate that mice lacking the homeobox transcription factor engrailed-2 (En2 −/− mice) represent a reliable model to investigate neurodevelopmental basis and gene expression changes relevant to autism spectrum disorders. Dysfunctions in fragile X mental retardation protein (FMRP), metabotropic glutamate receptor 5 (mGluR5), and GABAergic signaling pathways have been proposed as a possible pathogenic mechanism of autism spectrum disorders. Here, we exploited En2 −/− mice to investigate hippocampal expression of FMRP, mGluR5, and GABAA receptor β3 subunit (GABRB3). Quantitative reverse-transcription PCR showed that all these mRNAs were significantly downregulated in En2 −/− mice compared with wild-type littermates. Western blot and immunohistochemistry confirmed the downregulation of FMRP and GABRB3 proteins, while showing a significant increase of mGluR5 protein in the En2 −/− hippocampus. Our results suggest that the dysregulation of FMRP–mGluR5 signaling pathway, accompanied with a downregulation of GABRB3 expression, may contribute to the 'autistic-like' features observed in En2 −/− mice, providing possible molecular targets for future pharmacological studies.