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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
Rhizophora mucronata attenuates beta-amyloid induced cognitive dysfunction, oxidative stress and cholinergic deficit
Natarajan Suganthy1, Dicson Sheeja Malar1, Kasi Pandima Devi2
1Department of Biotechnology, Alagappa University, Karaikudi, Tamil Nadu, 630 003, India.
Abstract:
Alzheimer's disease (AD) is a progressive neurodegenerative disorder, characterized by accumulation and deposition of Aβ peptide in human brain. The present study aimed to determine the protective effect of catechin rich extract of MERM (methanolic extract of Rhizophora mucronata) on Aβ (25-35) induced cognitive impairment and neuronal toxicity in mice. In the present study AD characteristics were induced by intracerberoventricular administration of aggregated Aβ (25-35) in the Swiss albino mice. Learning and memory deficits were assessed using behavioral assays such as Morris water maze, Y-maze and step down avoidance tasks. Oxidative stress mediated impairment were assessed by measuring the activities of enzymatic and non-enzymatic antioxidants, level of apoptotic protein and oxidative markers in the hippocampus and frontal cortex region. Histolopathological analysis of brain was also carried out. Results illustrated that oral treatment of MERM (200 and 400 mg/kg bw) significantly attenuated Aβ (25-35) induced memory impairment as evaluated by behavioral tests. In addition treatment with MERM attenuated the elevation of β-secretase activity accompanying the reduced level of Aβ (25-35) in the cortex and hippocampus of brain. MERM also enhanced the cognitive function by significantly inhibiting AChE, BuChE and MAO-B. Furthermore, MERM attenuated lipid peroxidation, protein oxidation, restored the antioxidant status and inhibited neuronal apoptosis by down-regulating the level of caspase 3 and Bax protein. These data suggest that MERM rich in catechin can act as promising drug for AD treatment because of its antioxidant, anti-apoptotic and reducing Aβ oligomer activities.
Insights
Rhizophora mucronata extract (MERM) shows promise for Alzheimer's disease (AD) treatment. It improved memory and reduced neuronal damage in mice by acting as an antioxidant and anti-apoptotic agent.
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-beta (Aβ) peptide accumulation.
- Current treatments for AD have limitations, necessitating the exploration of novel therapeutic agents.
Purpose of the Study:
- To investigate the protective effects of a catechin-rich methanolic extract of Rhizophora mucronata (MERM) against Aβ(25-35) induced cognitive impairment and neuronal toxicity in mice.
- To evaluate MERM's potential as a therapeutic agent for Alzheimer's disease.
Main Methods:
- Alzheimer's disease characteristics were induced in Swiss albino mice via intra-cerebroventricular administration of aggregated Aβ(25-35).
- Cognitive function was assessed using behavioral tests (Morris water maze, Y-maze, step-down avoidance).
- Oxidative stress markers, antioxidant enzyme activities, and apoptotic protein levels in brain tissues were analyzed.
Main Results:
- Oral administration of MERM (200 and 400 mg/kg) significantly ameliorated Aβ(25-35) induced memory deficits.
- MERM treatment reduced β-secretase activity and Aβ(25-35) levels, while inhibiting acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and monoamine oxidase-B (MAO-B).
- MERM attenuated lipid peroxidation and protein oxidation, restored antioxidant status, and inhibited neuronal apoptosis by down-regulating caspase 3 and Bax protein.
Conclusions:
- The catechin-rich MERM exhibits significant antioxidant, anti-apoptotic, and Aβ oligomer-reducing activities.
- MERM demonstrates potential as a promising therapeutic agent for Alzheimer's disease treatment.
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