| Autor: |
Castro-Hernández, Ricardo, Berulava, Tea, Metelova, Maria, Epple, Robert, Centeno, Tonatiuh Peña, Richter, Julia, Kaurani, Lalit, Pradhan, Ranjit, Sakib, M. Sadman, Burkhardt, Susanne, Ninov, Momchil, Bohnsack, Katherine E., Bohnsack, Markus T., Delalle, Ivana, Fischer, Andre |
| Předmět: |
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| Zdroj: |
Proceedings of the National Academy of Sciences of the United States of America; 2/28/2023, Vol. 120 Issue 9, p1-12, 36p |
| Abstrakt: |
N6 -methyladenosine (m6 A) regulates mRNA metabolism. While it has been implicated in the development of the mammalian brain and in cognition, the role of m6 A in synaptic plasticity, especially during cognitive decline, is not fully understood. In this study, we employed methylated RNA immunoprecipitation sequencing to obtain the m6 A epitranscriptome of the hippocampal subregions CA1, CA3, and the dentate gyrus and the anterior cingulate cortex (ACC) in young and aged mice. We observed a decrease in m6 A levels in aged animals. Comparative analysis of cingulate cortex (CC) brain tissue from cognitively intact human subjects and Alzheimer’s disease (AD) patients showed decreased m6 A RNA methylation in AD patients. m6 A changes common to brains of aged mice and AD patients were found in transcripts linked to synaptic function including calcium/calmodulin-dependent protein kinase 2 (CAMKII) and AMPA-selective glutamate receptor 1 (Glua1). We used proximity ligation assays to show that reduced m6 A levels result in decreased synaptic protein synthesis as exemplified by CAMKII and GLUA1. Moreover, reduced m6 A levels impaired synaptic function. Our results suggest that m6 A RNA methylation controls synaptic protein synthesis and may play a role in cognitive decline associated with aging and AD. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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