| dc.description.abstract | Abstract
The capacity to form and store new memories is one of the most important cognitive ability that characterizes the human brain. At the same time, is one of the brain faculties most affected by neurodegenerative disease. The molecular mechanism underlying memory formation remains to this day unclear. Understanding how memories are formed would bring us one step closer in reversing the cognitive decline caused by neurodegeneration. During the last decade, it has been widely acknowledged that changes in the epigenetic landscape contribute to memory encoding molecular events. On the other side, neurodegenerative diseases are characterized by accumulation of oxidative stress which leads to accumulation of oxidative DNA lesions. Ogg1 and Mutyh are two DNA glycosylases responsible for the repairment of oxidative lesions and maintenance of neuronal integrity. Recent findings have demonstrated that Ogg1 and Mutyh may be involved in epigenetic-mediated gene expression and have also been associated with cognitive impairment.
Therefore, this study was designed to investigate a non-canonical function of Ogg1 and Mutyh in memory formation. In the study we used Ogg1 and Mutyh knockout mouse model to investigate epigenetic alterations in the prefrontal cortex (PFC). In addition, behavioral testing was applied to assess differences in memory retention as a result of Ogg1 and Mutyh deficiency. We found that loss of Ogg1 alters global hydroxymethylation levels in PFC, indicating that Ogg1 plays an important role in epigenetic regulation. As well, we found that Ogg1 and Mutyh deficiency affects expression levels of histone marks and PRC2 proteins, suggesting that Ogg1 and Mutyh potentially regulates PRC2 activity in the cortex.
Taken together, all our findings indicate that Ogg1 and Mutyh DNA glycosylases are involved in epigenetic alterations that might be important in regulating memory formation | |