| Autor: |
Thomas K Creson, Camilo Rojas, Ernie Hwaun, Thomas Vaissiere, Murat Kilinc, Andres Jimenez-Gomez, Jimmy Lloyd Holder Jr, Jianrong Tang, Laura L Colgin, Courtney A Miller, Gavin Rumbaugh |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
|
| Zdroj: |
eLife, Vol 8 (2019) |
| Druh dokumentu: |
article |
| ISSN: |
2050-084X |
| DOI: |
10.7554/eLife.46752 |
| Popis: |
It remains unclear to what extent neurodevelopmental disorder (NDD) risk genes retain functions into adulthood and how they may influence disease phenotypes. SYNGAP1 haploinsufficiency causes a severe NDD defined by autistic traits, cognitive impairment, and epilepsy. To determine if this gene retains therapeutically-relevant biological functions into adulthood, we performed a gene restoration technique in a mouse model for SYNGAP1 haploinsufficiency. Adult restoration of SynGAP protein improved behavioral and electrophysiological measures of memory and seizure. This included the elimination of interictal events that worsened during sleep. These events may be a biomarker for generalized cortical dysfunction in SYNGAP1 disorders because they also worsened during sleep in the human patient population. We conclude that SynGAP protein retains biological functions throughout adulthood and that non-developmental functions may contribute to disease phenotypes. Thus, treatments that target debilitating aspects of severe NDDs, such as medically-refractory seizures and cognitive impairment, may be effective in adult patients. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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