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EnglishMany 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.
| Titolo: | Hippocampal dysregulation of FMRP/mGluR5 signaling in engrailed-2 knockout mice: a model of autism spectrum disorders |
| Autori: | Provenzano, Giovanni; Sgadò, Paola; Genovesi, Sacha; Zunino, Giulia; Casarosa, Simona; Bozzi, Yuri |
| Autori Unitn: | |
| Titolo del periodico: | NEUROREPORT |
| Anno di pubblicazione: | 2015 |
| Numero e parte del fascicolo: | 18 |
| Codice identificativo Scopus: | 2-s2.0-84983027706 |
| Codice identificativo Pubmed: | 26559723 |
| Codice identificativo ISI: | WOS:000365514700004 |
| Digital Object Identifier (DOI): | http://dx.doi.org/10.1097/WNR.0000000000000477 |
| Handle: | http://hdl.handle.net/11572/126061 |
| Appare nelle tipologie: | 03.1 Articolo su rivista (Journal article) |
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