Abstract TP233: Cerebroprotective Role Of M 6 A Demethylase Fat Mass And Obesity-associated Protein After Experimental Stroke
| Autor: | Raghu Vemuganti, Anil K Chokkalla, Soomin Jeong, Suresh L Mehta, Kahlilia Morris-Blanco, Saivenkateshkomal Bathula, Simran Qureshi |
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| Rok vydání: | 2023 |
| Předmět: | |
| Zdroj: | Stroke. 54 |
| ISSN: | 1524-4628 0039-2499 |
| Popis: | Fat mass and obesity-associated protein (FTO) demethylates N 6 -methyladenosine (m 6 A), which is a critical epitranscriptomic regulator of neuronal function. We previously reported that ischemic stroke induces m 6 A hypermethylation with a simultaneous decrease in FTO expression in the neurons. Currently, we evaluated the functional significance of restoring FTO with an adeno-associated virus 9 (AAV9), and thus reducing m 6 A methylation in the post-stroke brain damage. Adult male and female C57BL/6J mice were injected with FTO AAV9 (intracerebral) at 21 days prior to inducing transient middle cerebral artery occlusion. Post-stroke brain damage (infarction, atrophy and white matter integrity) and neurobehavioral deficits (motor function, cognition, depression and anxiety-like behaviors) were evaluated between days 1 and 28 of reperfusion. FTO overexpression significantly decreased the post-stroke m 6 A hypermethylation. More importantly, exogenous FTO substantially decreased post-stroke grey and white matter damage and improved motor function recovery, cognition and depression-like behavior in both sexes. These results demonstrate that FTO-dependent m 6 A demethylation minimizes long-term sequelae of stroke independent of sex. |
| Databáze: | OpenAIRE |
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