Serotonin 5-HT7 receptors require cyclin-dependent kinase 5 to rescue hippocampal synaptic plasticity in a mouse model of Fragile X Syndrome.
| Autor: | Costa L; Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy., Tempio A; Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy., Lacivita E; Department of Pharmacy, University of Bari, Bari, Italy., Leopoldo M; Department of Pharmacy, University of Bari, Bari, Italy., Ciranna L; Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy. |
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| Jazyk: | angličtina |
| Zdroj: | The European journal of neuroscience [Eur J Neurosci] 2021 May 05. Date of Electronic Publication: 2021 May 05. |
| DOI: | 10.1111/ejn.15246 |
| Abstrakt: | Fragile X Syndrome is a genetic form of intellectual disability associated with autism, epilepsy and mood disorders. Electrophysiology studies in Fmr1 knockout (KO) mice, a murine model of Fragile X Syndrome, have demonstrated alterations of synaptic plasticity, with exaggerated long-term depression induced by activation of metabotropic glutamate receptors (mGluR-LTD) in Fmr1 KO hippocampus. We have previously demonstrated that activation of serotonin 5-HT7 receptors reverses mGluR-LTD in the hippocampus of wild-type and Fmr1 KO mice, thus correcting a synaptic dysfunction typically observed in this disease model. Here we show that pharmacological inhibition of cyclin-dependent kinase 5 (Cdk5, a signaling molecule recently shown to be a modulator of brain synaptic plasticity) enhanced mGluR-LTD in wild-type hippocampal neurons, which became comparable to exaggerated mGluR-LTD observed in Fmr1 KO neurons. Furthermore, Cdk5 inhibition prevented 5-HT7 receptor-mediated reversal of mGluR-LTD both in wild-type and in Fmr1 KO neurons. Our results show that Cdk5 modulates hippocampal synaptic plasticity. 5-HT7 receptors require Cdk5 to modulate synaptic plasticity in wild-type and rescue abnormal plasticity in Fmr1 KO neurons, pointing out Cdk5 as a possible novel target in Fragile X Syndrome. (© 2021 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.) |
| Databáze: | MEDLINE |
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