P2‐030: DPP‐4 inhibitor improves brain insulin sensitivity, but fails to restore hippocampal synaptic plasticity and cognitive function in testosterone‐deprived obese rats

neurons in the hippocampus by unbiased stereology. We also measured Amyloid beta (Ab) levels in hippocampal homogenates by dot-blot analysis. Results:Whole hippocampal volume was not different between Arg-61 and C57BL/6J mice; however, the granular cell layer (GCL) volume and the percentage it occupies in the hippocampus were larger in Arg-61 than in C57BL/6J mice. Subgranular zone (SGZ) calretinin (CR)-positive neuron number and density were higher in Arg-61 mice, but the Cr positive mossy fiber layer is significantly reduced, suggesting that the larger GCL volumemay result frommore immature cells having less functional calretinin positive nerve fibers, being added to the GCL. Lastly, Ab –which stimulates ectopic adult neurogenesis in mouse models of Alzheimer disease, was significantly higher in Arg-61 than in C57BL/6J mice. Conclusions: In conclusion, impaired cognitive functions in young Arg-61 mice may do not result from lower hippocampal volume. In contrast, the larger GCL volume and higher calretinin cell number and density suggest a high proliferative compensatory attempt due to amyloid beta perturbations, and resulting in an impaired nerve fiber growth and signal transduction. These results may suggest a mechanism involved in apoE4 induced neuro-pathogenesis. These results also suggest that targeting apoEε4 domain interaction may thus be a viable prophylactic/therapeutic approach for apoEε4-dependent pathologies and increased susceptibility of apoEε4 subjects to AD.