DNA damage is proposed to be the reason for mutations to occur. Base excision repair (BER) is the main pathway utilized by the brain to repair oxidative DNA damage. Defects in BER have been linked to the development of neurodegenerative diseases. NEIL3-/- is one of the glycosylases that initiates this pathway. Interestingly, NEIL3-depleted mice are viable and with normal lifespan but show impaired spatial learning and memory phenotypes in Morris water maze behavioral task. The hippocampal formation and the medial entorhinal cortex are regions in the mammalian brain important for spatial cognition. Recently, NEIL3 has been shown to play a role in adult neurogenesis as well as induced neurogenesis in newborn mice after stroke.
In this study we aimed to investigate the impact of NEIL3 on postnatal development in the hippocampal formation (HF) and neuronal organization in the entorhinal-hippocampal spatial representation system. We monitored maturation and organization of distinct neuronal populations in sub regions of the hippocampal formation (HF) and sublayers of the medial entorhinal cortex (MEC) during the first postnatal month as well as in the 3- and 12-month old mice. We used immunohistochemistry (IHC) combined with confocal microscopy and software-guided cell counting.
Our results show that: (1) Proliferation and differentiation of cells in the subgranular zone (SVG) of the dentate gyrus (DG) are normal in newborn mice lacking NEIL3. (2) Postnatal maturation in the DG is delayed in NEIL3-/- mice. (3) Neurons in CA1/CA3 of the hippocampus mature earlier than DG. Our results also suggest delayed maturation in NEIL3-/- mice in the first postnatal month.
(4) However, similar number of mature hippocampal and entorhinal neurons were identified in the adult wildtype and NEIL3-/- mice (5) No obvious difference of hippocampal and entorhinal neurons were found in 3m and 12m old NEIL3-/- mice.
The results implicate an essential role of NEIL3 in the postnatal maturation of the hippocampus.