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Intracerebroventricular Injection of Amyloid-β Peptides in Normal Mice to Acutely Induce Alzheimer-like Cognitive Deficits
Published on: March 16, 2016
Protective effect of meloxicam-loaded nanocapsules against amyloid-β peptide-induced damage in mice
Francine R Ianiski1, Catiane B Alves, Ana Cristina G Souza
1Mestrado em Nanociências, Centro de Ciências Tecnológicas, Centro Universitário Franciscano, Santa Maria, CEP 97010-032, RS, Brazil.
Abstract:
The objective of present study was to investigate the protective effect of M-NC against aβ (25-35) peptide-induced damage in mice, as the first step to evaluate their potential value for the treatment of AD. Moreover, we compared the effects of M-NC with free meloxicam (M-F). Mice were divided into six groups: (I) sham, (II) aβ, (III) M-NC, (IV) M-F, (V) M-NC+aβ and (VI) M-F+aβ. Mice were pre-treated with M-NC (5mg/kg, by gavage), M-F (5mg/kg, by gavage) or blank nanocapsules (B-NC). Thirty minutes after treatments, aβ peptide (3nmol) or filtered water were i.c.v. injected. Learning and memory were assessed with the Morris water maze (MWM) (days 4-7) and step-down-type passive-avoidance (SDPA) (days 7-8) tasks. At the end of the experimental protocol (day 8), animals were euthanized and brains were removed for biochemical determinations (reactive species (RS), non-protein thiols (NPSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST)) and histological examination. Our results confirmed that aβ peptide caused learning and memory deficits in mice. Histological analysis demonstrated neuronal loss, intense cellular accumulation and chromatolysis caused by aβ peptide. Furthermore, this study showed that oxidative stress was increased in mice that received aβ peptide. An important finding of the present study was the protective effect of M-NC in damage induced by aβ peptide. However, M-F did not have protective effect. In summary, the data reported herein clearly demonstrate that meloxicam carried by polymeric nanocapsules protected against learning and memory impairments, loss neuronal and oxidative stress in a mouse model of AD induced by aβ peptide.
Insights
Polymeric nanocapsules carrying meloxicam (M-NC) demonstrated significant neuroprotective effects against amyloid-beta peptide-induced damage in a mouse model of Alzheimer's disease (AD). M-NC treatment improved learning, memory, and reduced oxidative stress, unlike free meloxicam.
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline.
- Amyloid-beta (Aβ) peptide aggregation is a key pathological hallmark of AD, inducing neuronal damage and oxidative stress.
- Meloxicam, a non-steroidal anti-inflammatory drug, has shown potential but requires optimized delivery for neuroprotection.
Purpose of the Study:
- To investigate the neuroprotective efficacy of meloxicam-loaded polymeric nanocapsules (M-NC) against Aβ(25-35) peptide-induced neurotoxicity in mice.
- To compare the therapeutic potential of M-NC with free meloxicam (M-F) in an AD mouse model.
- To evaluate the impact of M-NC on cognitive function, neuronal integrity, and oxidative stress markers.
Main Methods:
- Mice were treated with M-NC, M-F, or blank nanocapsules before intracerebroventricular (ICV) injection of Aβ(25-35) peptide.
- Cognitive performance was assessed using the Morris water maze (MWM) and step-down passive avoidance (SDPA) tasks.
- Post-mortem brain tissue analysis included biochemical assays for oxidative stress markers and histological examination for neuronal damage.
Main Results:
- Aβ(25-35) peptide injection induced significant learning and memory deficits, neuronal loss, and increased oxidative stress in mice.
- Pre-treatment with M-NC significantly ameliorated cognitive impairments and protected against Aβ-induced neuronal damage.
- M-NC treatment effectively reduced oxidative stress markers, while M-F showed no significant protective effect.
Conclusions:
- Meloxicam encapsulated in polymeric nanocapsules (M-NC) exhibits potent neuroprotective properties against Aβ-induced neurodegeneration.
- M-NC represents a promising therapeutic strategy for mitigating cognitive decline and neuronal damage in Alzheimer's disease.
- Nanoparticle-based drug delivery enhances the therapeutic efficacy of meloxicam for neurodegenerative disorders.
