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Establishment of a Valuable Mimic of Alzheimer's Disease in Rat Animal Model by Intracerebroventricular Injection of Composited Amyloid Beta Protein
Published on: July 29, 2018
Aβ(42) induced MRI changes in aged rabbit brain resembles AD brain
B N Ramesh1, K P Raichurkar, N M Shamasundar
1Department of Biochemistry and Nutrition, CFTRI, Mysore, India.
Abstract:
Alzheimer's disease is the most common form of dementia and is structurally characterized by brain atrophy and loss of brain volume. Aβ is one of the widely accepted causative factors of AD. Aβ deposition is positively correlated with brain atrophy in AD. In the present study, structural brain imaging techniques such as Magnetic Resonance Imaging (MRI) were used to measure neuroanatomical alterations in Alzheimer's disease brain. MRI is a non-invasive method to study brain structure. The objective of the present study was to elucidate the role of Aβ on brain structure in the aged rabbit brain. Among 20 aged rabbits, one batch (n=10) rabbits was injected chronically with Aβ(1-42) and another batch (n=10) with saline. The MRI was conducted before Aβ(1-42)/saline injection and after 45 days of Aβ(1-42)/saline injection. All the aged rabbits underwent MRI analysis and were euthanized after 45 days. The MRI results showed a significant reduction in thickness of frontal lobe, hippocampus, midbrain, temporal lobe and increases in the lateral ventricle volume. We also conducted an MRI study on AD (n=10) and normal (n=10) cases and analyzed for the thicknesses of frontal lobe, hippocampus, midbrain, temporal lobe and lateral ventricle lobe. We found significant reductions in thickness of the frontal lobe and the hippocampus. However, no significant reduction in the thickness of midbrain, temporal lobe or increase in the lateral ventricle volume was observed compared to normal. Correlations in brain atrophy changes between rabbit brain and human AD brain were found for frontal lobe and hippocampal regions. In contrast, other regions such as midbrain, temporal lobe, and lateral ventricles were not correlated with rabbit brain atrophy changes in the corresponding regions. The relevance of these changes in AD is discussed.
Insights
Amyloid-beta (Aβ) injections in aged rabbits caused brain atrophy, particularly in the frontal lobe and hippocampus, mirroring changes seen in human Alzheimer's disease (AD) brains. This suggests Aβ plays a key role in AD-related neurodegeneration.
Area of Science:
- Neuroscience
- Neurodegenerative Diseases
- Biomedical Imaging
Background:
- Alzheimer's disease (AD) is a leading cause of dementia, characterized by brain atrophy and volume loss.
- Amyloid-beta (Aβ) deposition is a key pathological hallmark of AD and is correlated with brain atrophy.
- Structural brain imaging, such as Magnetic Resonance Imaging (MRI), is crucial for assessing neuroanatomical alterations.
Purpose of the Study:
- To investigate the causal role of Aβ in inducing brain structural changes.
- To compare Aβ-induced neuroanatomical alterations in an aged rabbit model with human AD brain changes.
- To elucidate the specific brain regions affected by Aβ deposition using MRI.
Main Methods:
- Chronic intracerebral injection of Aβ(1-42) or saline into aged rabbits (n=10 per group).
- Serial MRI scans were performed before and 45 days after injection to measure brain structure.
- Comparative MRI analysis was conducted on human AD patients (n=10) and healthy controls (n=10).
Main Results:
- Aβ(1-42) injection in rabbits led to significant reductions in frontal lobe and hippocampus thickness, and increased lateral ventricle volume.
- Human AD brains showed significant reductions in frontal lobe and hippocampus thickness compared to controls.
- Brain atrophy patterns in the frontal lobe and hippocampus of rabbits correlated with those observed in human AD brains.
Conclusions:
- Aβ(1-42) administration induces structural brain changes in rabbits that partially mimic human Alzheimer's disease.
- The frontal lobe and hippocampus are critical regions affected by Aβ-induced neurodegeneration in both rabbits and humans.
- The aged rabbit model provides a valuable platform for studying Aβ-related brain atrophy and potential therapeutic interventions for AD.
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