(MDPI, 2017) Palomino Alonso, Maialen; Lachén Montes, Mercedes; González Morales, Andrea; Ausín, Karina; Pérez Mediavilla, Alberto; Fernández Irigoyen, Joaquín; Santamaría Martínez, Enrique; Ciencias de la Salud; Osasun Zientziak; Gobierno de Navarra / Nafarroako Gobernua, PC023-24; Universidad Pública de Navarra / Nafarroako Unibertsitate Publikoa
Olfaction is often deregulated in Alzheimer’s disease (AD) patients, and is also impaired
in transgenic Tg2576 AD mice, which overexpress the Swedish mutated form of human amyloid
precursor protein (APP). However, little is known about the molecular mechanisms that accompany
the neurodegeneration of olfactory structures in aged Tg2576 mice. For that, we have applied
proteome- and transcriptome-wide approaches to probe molecular disturbances in the olfactory
bulb (OB) dissected from aged Tg2576 mice (18 months of age) as compared to those of age
matched wild-type (WT) littermates. Some over-represented biological functions were directly
relevant to neuronal homeostasis and processes of learning, cognition, and behavior. In addition
to the modulation of CAMP responsive element binding protein 1 (CREB1) and APP interactomes,
an imbalance in the functionality of the IκBα-NFκB p65 complex was observed during the aging
process in the OB of Tg2576 mice. At two months of age, the phosphorylated isoforms of olfactory
IκBα and NFκB p65 were inversely regulated in transgenic mice. However, both phosphorylated
proteins were increased at 6 months of age, while a specific drop in IκBα levels was detected in
18-month-old Tg2576 mice, suggesting a transient activation of NFκB in the OB of Tg2576 mice. Taken
together, our data provide a metabolic map of olfactory alterations in aged Tg2576 mice, reflecting the
progressive effect of APP overproduction and β-amyloid (Aβ) accumulation on the OB homeostasis
in aged stages.
