A Circular RNA Regulates SYP Expression to Improve Memory Function in Mice

Researchers here note that SYP expression declines with age and is involved in mammalian memory function. They find a circular RNA that uprgulates SYP expression, and use it to improve memory in a mouse model. Unfortunately the study didn't use normally aged mice, but rather an artificial model of chemically induced damage as accelerated aging. Nonetheless, there is sufficient existing evidence for the role of SYP to think that the results of this study support running a test in normally aged mice to see if a similar positive outcome can be achieved there.

Age is an established risk factor for neurodegenerative disorders. Aging-related cognitive decline is a common cause of memory impairment in aging individuals, in which hippocampal synaptic plasticity and hippocampus-dependent memory formation are damaged. Circular RNAs (circRNAs) have been reported in many cognitive disorders, but their role in aging-related memory impairment is unclear. In this study, we aimed to investigate the effects of circ-Vps41 on aging-related hippocampus-dependent memory impairment and explore the potential mechanisms. Here, D-galactose was used to produce a conventional aging model resulting in memory dysfunction.

Circ-Vps41 was significantly downregulated in D-galactose-induced aging in vitro and in vivo. The overexpression of circ-Vps41 could upregulate synaptophysin (Syp), thereby promoting the synaptic plasticity and alleviating cognitive impairment in aging mice. Mechanistically, we found that circ-Vps41 upregulated Syp expression by physically binding to miR-24-3p. Moreover, the miR-24-3p mimics reversed the circ-Vps41 overexpression-induced increase in Syp expression.

In conclusion, overexpression of circ-Vps41 alleviated the synaptic plasticity and memory dysfunction via the miR-24-3p/Syp axis. These findings revealed circ-Vps41 regulatory network and provided new insights into its potential mechanisms for improving aging-related learning and memory impairment.

Link: https://doi.org/10.3389/fnmol.2022.1037912