MINOCYCLINE IMPROVES MEMORY AND REDUCES THE NEUROINFLAMMATION OF MICE SUBJECT TO AMYLOID B (1-42) PEPTIDE ADMINISTRATION

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder that the main risk factor is age. The cognitive decline and neuroinflammation are the major hallmark of this disease. Minocycline is a tetracycline derivative with anti-inflammatory properties that has a neuroprotective capability by limiting inflammation and oxidative stress. Therefore, the aim this study was to evaluate the involvement of minocycline in memory and neuroinflammation in an animal model of AD induces by amyloid β peptide administration. Male BALB/c mice (3 month-old) were subjected to intracerebroventricular amyloid β (1-42) peptide (400pmol) administration and treated with minocycline (50mg/kg) by oral route for 17 days. The animals were subjected to radial maze test in the 14th to 17th. The animals were killed in the 18th day, 24 hour after the last minocycline administration, and frontal cortex and hippocampus tissues were removed for biochemical analysis. Mice that received the amyloid β (1-42) peptide showed damage in the spatial memory. Minocycline administration reversed this cognitive decline. In the hippocampus, amyloid β (1-42) peptide induced an increase of pro-inflammatory (IL-1β and TNF-α) and anti-inflammatory (IL-4 and IL-10) cytokines levels. Minocycline reversed the increase of IL-1β, TNF-α and, IL-10 levels in this tissue. In the frontal cortex, the IL-1β, TNF-α and, IL-4 levels were increased by amyloid β (1-42) peptide administration. These effects were reversed by minocycline administration. The IL-10 level did not change in this brain tissue. Therefore, the results indicated that minocycline improves the spatial memory observed in the radial maze task acomppanied by reduction of pro-inflammatory and anti-inflammatory cytokines levels in the brain tissue.