Celecoxib Prevents Cognitive Impairment and Neuroinflammation in Soluble Amyloid β-treated Rats

Recent findings suggest that soluble forms of amyloid-beta (sA beta) peptide contribute to synaptic and cognitive dysfunctions in early stages of Alzheimer's disease (AD). On the other hand, neuroinflammation and cyclooxygenase-2 (COX-2) enzyme have gained increased interest as key factors involved early in AD, although the signaling pathways and pathophysiologic mechanisms underlying a link between sA beta-induced neurotoxicity and inflammation are still unclear. Here, we investigated the effects of selective COX-2 enzyme inhibition on neuropathological alterations induced by sA beta administration in rats. To this purpose, animals received an intracere-broventricular (icv) injection of predominantly monomeric forms of sA beta and, 7 days after, behavioral as well as biochemical parameters and neurotransmitter alterations were evaluated. During this period, rats also received a sub-chronic treatment with celecoxib. Biochemical results demonstrated that icv sA beta injection significantly increased both COX-2 and pro-inflammatory cytokines expression in the hippocampus (Hipp) of treated rats. In addition, the number of hypertrophic microglial cells and astrocytes were upregulated in sA beta-treated group. Interestingly, rats treated with sA beta showed long-term memory deficits, as confirmed by a significant reduction of discrimination index in the novel object recognition test, along with reduced brain-derived neurotrophic factor expression and increased noradrenaline levels in the Hipp. Systemic administration of celecoxib prevented behavioral dysfunctions, as well as biochemical and neurotransmitter alterations. In conclusion, our results suggest that sA beta neurotoxicity might be associated to COX-2-mediated inflammatory pathways and that early treatment with selective COX-2 inhibitor might provide potential remedies to counterbalance the sA beta-induced effects. (C) 2018 IBRO. Published by Elsevier Ltd. All rights reserved.