Propriedade de membrana de neurônios do giro denteado em camundongos sem a enzima de reparo de DNA NEIL3

Abstract

This study aims to assess whether the expression of the DNA repair enzyme Neil3 is important for the functional development of neurons. Previous studies have demonstrated that Neil3 interferes with both adult and embryonic neurogenesis. I have used whole cell patch clamp to study membrane and synaptic properties of granule cells of the dentate gyrus. The dentate gyrus is one of the regions with the highest expression of Neil3 in the brain, and previous studies have shown that reactive neurogenesis in adult mice is affected by Neil3 deletion. I found that most membrane properties of granule cells in Neil3-knockout mice are normal except from the membrane response to hyperpolarization currents and afterhyperpolarization currents. Different from immature neurons, granule cells of the dentate gyrus from Neil3-knockout mice, in which hyperpolarizing activated currents, are generally the last to appear during development. In addition, excitatory synaptic currents were similar in amplitude but showed a slightly faster decay in cells from Neil3-knockout mice. These results could indicate a different balance between AMPA and NMDA receptors in Neil3-knockout mice cells. Morphological analysis of neurons filled with biocytin and reconstructed post hoc showed no gross difference in dendritic morphology between dentate gyrus neurons of control and Neil3-knockout mice. This study shows that, while different from those of control littermates, dentate gyrus neurons of Neil3-knockout mice cannot be classified as ‘immature’. I found specific differences in hyperpolarizing activated currents and small differences in synaptic properties. Whether these differences may account for behavioral changes found in Neil3-knockout mice is yet to be assessed. In addition, future studies using markers of newly born neurons are necessary for analyzing the effect of Neil3 deletion in developing neurons.