Daily temporal organization of inflammation and cognition-related factors and antioxidant enzymes are modified by an intracerebroventricular injection of amyloid-beta peptide (1–42) aggregates in the rat temporal cortex

Abstract

adults. The neuropathological hallmarks of AD include amyloid plaques, neurofibrillary tangles, oxidativedamage, neuroinflammation, synaptic loss and neuronal cell death. The accumulation of Aβ in the brain plays akey role in the pathogenesis of AD. Elevated levels of Aβ causes an increase in oxidative damage and neuroinflammationboth are considered key factors in the progression of AD. Also patients with Alzheimer?s showalterations in their circadian rhythms. Our objectives were (a) to analyze whether inflammation and cognitionrelatedfactors exhibit a day-night variation, (b) to verify whether antioxidant enzymes expression and activityexhibit a daily rhythm in the rat temporal cortex and (c) to evaluate the effects of an intracerebroventricularinjection of Aβ-amyloid (1?42) aggregates on those temporal profiles. Four-month old males Holtzman rats wereused in this study. Groups were defined as: 1) control 2) Aβ-injected. Rats were maintained under 12 h-Light:12 h-Dark conditions with food ad-libitum. Our results showed temporal patterns of nitrites, iNOS, catalaseand glutathione peroxidase expression and activity, as well as Rc3 and Gap-43 mRNA, in the rat temporal cortex.An i.c.v. injection of Aβ abolishes the temporal pattern of Rc3 and Gap-43 mRNA. Also increased the rhythm?smesor of NO and iNOS levels, reduced the mesor of CAT activity rhythms, and changed the phase of GPx activitypatterns. These alterations in the temporal patterns of inflammation and redox status-related factors would affectcellular clock activity and consequently cognitive performance.