Effects of Lansoprazole administration on hippocampal cell apoptosis, learning and memory deficits in adult rats via activated of Tau Phosphorylation, Aβ (1–42) Pathway

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative condition marked by memory loss and dementia, caused by changes in the cortical milieu, such as neuroinflammation, oxidative stress, and accumulation of beta-amyloid (Aβ) in the brain. The drug-induced cognitive impairment is more common in the elderly than in younger people. The research-using valid animal models may help determine the effective and safe medicine for AD treatment. Studies have found that patients who used lansoprazole for long-term therapy for ulcers, Zollinger-Ellison syndrome, and gastroesophageal reflux disease (GERD) who may suffer from memory problems. The novel research was designed to check whether lansoprazole administration to rats may enhance oxidative stress, Aβ accumulation and neurodegeneration. In the current study, rats were given lansoprazole at doses of 15 and 30 mg/kg p.o. for 28 days. The Morris water maze and Probe trial were used to assess rats spatial and recognition memory deficits. On day 29, the rats were sacrificed, and the brain (hippocampus) was used to test for biochemicals (glutathione, superoxide dismutase, catalase, lipid peroxidation, and nitrite), neuroinflammatory markers (IL-1β, TNF-α & IL-6) neurotransmitters (ACh, GABA, and Glutamate), Aβ(1–42) level, nuclear factor-kappa B (NF-κB) analysis, and blood-brain barrier (BBB) disruption activity. Lansoprazole administrated raised inflammatory cytokines release, oxidative stress, altered neurotransmitter concentration, tau protein phosphorylation, and promoted the Aβ accumulation in the brain. These findings showed that lansoprazole treatment for four weeks caused neurobiological alteration in rats and degeneration of the endogenous antioxidant defense system.