371. AAV9-Mediated Over-Expression of Hippocampal Neuritin Prevents Extremely Low-Frequency Electromagnetic Field Exposure-Induced Impairment of Recognition Memory

Abstract

Extremely low-frequency (50Hz) electromagnetic fields (ELF MFs) are ubiquitously present in various environments during daily life. The major sources of ELF MFs pertaining to the general public are in-house installations, household appliances and power lines. Animal studies have shown that ELF MFs exposure may interfere with the activity of brain cells, thereby generating behavioral and cognitive disturbances. However, the underlying mechanisms and possible preventions are still unknown. In our preliminary studies, we found that ICR mice that were exposed to ELF MFs had deficits in hippocampus-dependent recognition memory but no concurrent changes in their locomotor activity. Further experiments revealed that ELF MFs exposure reduced dendritic spine densities of hippocampal CA1 pyramidal cells. Meanwhile, there was no significant effect on dendritic spine diameter or length. Since previous work has shown that neuritin, an important neurotrophin, has the ability to increase the spine density of hippocampal pyramidal neurons, we decided to explore whether neuritin is capable of reversing ELF MFs exposure-induced decreases in dendritic spine density. To this end, adeno-associated virus serotype 9 (AAV9) vectors carrying human neuritin cDNA were produced and stereotaxically injected into the CA1 region of the mouse hippocampus (0.2µl per mouse) 7 days before exposure to ELF MFs. Two control groups were injected in hippocampus with the same volume of AAV-GFP or saline. Western blot analysis indicated that the expression of neuritin was increased by 60.2 ± 5.8% in the hippocampus. We then quantified the effects of AAV9-mediated neuritin over-expression on hippocampal dendritic spine number and subsequent recognition memory in mice of both non-ELF MFs and ELF MFs exposure groups. After a 2.5-week infection period, a significant increase in spine density was observed in the AAV-neuritin group. On the other hand, there was no significant difference in dendritic diameter or length among all three groups of mice. Additionally, after ELF MFs exposure (1mT) for 12 h/day for 10 days, the spine density of pyramidal neurons obtained from neuritin-overexpression mice was no longer reduced. Consequently, the recognition memory test of AAV-neuritin mice showed a significant increase in recognition index when compared to AAV-control mice. Collectively, our study provided evidence for the association between ELF MFs exposure, impairment of recognition memory, and resulting changes in hippocampal dendritic spine density. Furthermore, overexpression of neuritin has the ability to prevent the ELF MFs-exposure-induced effect by increasing the hippocampal spine density.