Arc/Arg3.1 expression in the brain tissues during the learning process in Alzheimer's disease animal models

Abstract

Introduction. Arc/Arg3.1 is a common marker of neuronal activation for learning and memorizing. Some experimental data show the Arc/Arg3.1 expression in the post-mitotic neurons of the neurogenic niches. At the same time, we still have to understand the importance of such an expression for neurogenesis induced by the learning or memorizing processes, in health and in disease. Objective: to evaluate the changes in Arc/Arg3.1 expression in the post-mitotic neurons and to assess the proliferative activity of the neurogenic niche cells in Alzheimer's disease animal models. Materials and methods. We divided the C57Bl/6В mice into 2 groups: experimental (n = 15) and control (n = 15). The experimental group were injected with the amyloid- oligomers 2535 in their CA1 hippocampal region while the control mice received normal saline injections in the same region. Passive Avoidance Test (PAT) was used to assess the cognitive functions from the day 9 after the intervention. One hour after each test session we collected the samples of brain tissues to immunohistochemically assess them for the Arc/Arg3.1 expression and PCNA cell proliferation marker. Results. At day 11 the count of Arc/Arg3.1+NeuN+ cells in the subgranular zone had significantly increased. In animal neurodegeneration models the 1st and 2nd PAT sessions were associated with a significant increase in Arc/Arg3.1+NeuN+ cells, although by the day 11 their count significantly decreased. The count of Arc/Arg3.1+ cells in the subventricular and subgranular zones had increased after the 3rd PAT session in the control group while in Alzheimer's disease animal models this was observed only after the 2nd PAT session. Preserved Arc/Arg3.1 expression in the subventricular zone is associated with the increased PCNA cell prolifera- tion marker expression. At the same time, the toxic effect of the amyloid- oligomers suppressed the cells' proliferative activity in the subgranular zone at day 9. Conclusions. Despite the toxic effect of the amyloid- oligomers 2535, the post-mitotic neurons of the neurogenic niches retained the ability to express Arc/Arg3.1 in vivo. The obtained results show a transient increase in sensitivity of the post-mitotic neurons of the neurogenic niches for the learning stimuli in the early stages of the Alzheimer-type neurodegeneration.

Keywords

• arc/arg3.1
• alzheimer's disease
• plasticity
• neurogenesis
• neurogenic niche