Cognitive deficits and impaired hippocampal long-term potentiation in K ATP -induced DEND syndrome

Autor:	Zihan Yan, Steven Mennerick, Maria S. Remedi, Shaul Yahil, David F. Wozniak
Rok vydání:	2021
Předmět:	Multidisciplinary medicine.drug_class business.industry Cognition Long-term potentiation Hippocampal formation medicine.disease DEND syndrome Sulfonylurea Epilepsy Electrophysiology Diabetes mellitus medicine business Neuroscience
Zdroj:	Proceedings of the National Academy of Sciences. 118
ISSN:	1091-6490 0027-8424
DOI:	10.1073/pnas.2109721118
Popis:	Significance Gain-of-function (GOF) mutations in the ATP-sensitive potassium (K ATP ) channel cause neonatal diabetes, with some individuals exhibiting developmental delay, epilepsy, and neonatal diabetes (DEND) syndrome. In this study, we uncover the direct effects of neuronal expression of K ATP -GOF mutations, and not diabetes per se, on the neurological features of DEND. Our results show a close link between neuronal K ATP -GOF expression and cognitive dysfunction in DEND and reveal that antidiabetic sulfonylureas, which successfully treat diabetes, mitigate some sensorimotor problems but not cognitive deficits. These results have critical implications for humans, revealing the need for novel drugs to treat learning and memory deficits not only for K ATP -induced DEND but also for other pathologies arising from altered ion channels in the brain.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::7813966c5deddadf3ac00d7ba14a875d https://doi.org/10.1073/pnas.2109721118 Zobrazit plný text záznamu