51. β-Lapachone attenuates cognitive impairment and neuroinflammation in beta-amyloid induced mouse model of Alzheimer's disease
- Author
-
Pouran Karimi, Nadereh Rashtchizadeh, Narmin Mokarizadeh, Nazila Fathi Maroufi, Saeed Sadigh-Eteghad, and Marjan Erfani
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Inflammasomes ,Amyloid beta ,Immunology ,Anti-Inflammatory Agents ,Caspase 1 ,Hippocampal formation ,medicine.disease_cause ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Alzheimer Disease ,Internal medicine ,NLR Family, Pyrin Domain-Containing 3 Protein ,medicine ,Animals ,Humans ,Immunology and Allergy ,Cognitive Dysfunction ,Neuroinflammation ,Pharmacology ,Mice, Inbred BALB C ,Amyloid beta-Peptides ,biology ,Chemistry ,Dentate gyrus ,digestive, oral, and skin physiology ,Inflammasome ,Barnes maze ,Disease Models, Animal ,Oxidative Stress ,030104 developmental biology ,Endocrinology ,030220 oncology & carcinogenesis ,biology.protein ,Neurogenic Inflammation ,Oxidative stress ,Naphthoquinones ,medicine.drug - 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, and apoptosis cell death in the hippocampus. 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 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 down-regulate mRNA expression of NLRP3 inflammasome and protein levels of cleaved caspase 1 and IL-1β. Additionally, β-LAP-treated mice showed increased SIRT1 levels and NAD+/NADH ratio 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). These results indicated that the protective effect of β-LAP against AD-associated cognitive deficits is partially through its strong antioxidant and anti-inflammatory actions.
- Published
- 2020