Protective effects of β-Lapachone on cognitive function, neuronal inflammation and autophagy in Alzheimer's model mice induced by β amyloid

Abstract

Oxidative stress and neuroinflammation are critically involved in amyloid beta (Aβ) induced cognitive impairments. β-Lapachone (β-LAP) is a natural activator of NAD(P)H quinone oxidoreductase 1 (NQO1) which has antioxidant and anti-inflammatory properties. This study investigated the effect of β-LAP administration on Aβ-induced memory deficit, oxidative stress, neuroinflammation, apoptosis cell death and autophagic flux in the hippocampus. Methods: Forty BALB/c mice were allocated into control, sham, β-LAP (βL), Aβ, and Aβ + βL groups. Intracerebroventricular injection of Aβ1-42 was used to induce Alzheimer’s disease (AD) model. Mice in the βL and Aβ + βL groups were treated with β-LAP (10 mg/kg, i.p) for 4 days. Results:Results revealed that β-LAP attenuated memory impairment in the Aβ-received mice, as measured in the novel object recognition (NOR) and Barnes maze tests. Moreover, Aβ resulted in inflammasome activation evident by enhanced caspase-1 immunoreactivity and interleukin-1 beta (IL-1β) protein levels. However, β-LAP could markedly reduce reactive oxygen species (ROS) production and (38)autophagosomes accumulation. Additionally, β-LAP-treated mice showed increased NAD+/NADH ratio and SIRT1 levels in the hippocampus. These results were followed by fewer number of TUNEL-positive cell, reduced hippocampal atrophy and neuronal loss in the hippocampal dentate gyrus (DG).