Minocycline Ameliorated LPS-Induced Learning and Memory Impairment by Inhibiting Microglia and Astrocytes Activation in the Hippocampus

Abstract

INTRODUCTION: Many studies support the notion that neuroinflammation involving glial cells may be the fundamental pathogenic event that lead to brain damage and degeneration in Alzheimer’s disease (AD). The effects of minocycline on glial cells activation in the lipopolysaccharide (LPS) rat model is studied here. MATERIALS AND METHODS: Fifty adult male Sprague Dawley rats were split into five groups: control, LPS, LPS-treated with minocycline 25 mg/kg, LPS-treated with minocycline 50 mg/kg, and LPS treated with memantine 10 mg/kg. For two weeks, rats were treated with minocycline and memantine intraperitoneally daily, while were injected with LPS intraperitoneally once on day 5. Morris water maze (MWM) test was performed to evaluate the learning and working memory behaviour. Immunohistochemistry and Western blot were performed to measure ionized calcium-binding adaptor molecule 1 (Iba-1) and glial fibrillary acidic protein (GFAP) expressions in the hippocampal tissue. RESULTS: LPS injection caused significant learning and working memory deficits (p<0.05) as well as increased expressions of Iba-1 and GFAP (p<0.05), indicating microglia and astrocytes activation, respectively. Minocycline treatment significantly improved learning and working memory performance (p<0.05) and reduced microglia/astrocytes activation (p<0.05) in a dose-dependent manner, similar to the effect of memantine. CONCLUSIONS: Our results suggest that minocycline modulates LPS-induced microglia and astrocytes activation as well as improves learning and working memory comparable to memantine. Thus, minocycline may have  preventive-therapeutic effect in diseases involving neuroinflammation such as AD.