Specific reduction of calcium-binding protein (28-kilodalton calbindin-D) gene expression in aging and neurodegenerative diseases
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Preparation of Acute Hippocampal Slices from Rats and Transgenic Mice for the Study of Synaptic Alterations during Aging and Amyloid Pathology
Published on: March 23, 2011
1Department of Biochemistry and Molecular Biology, Graduate School of Biomedical Sciences, University of Medicine and Dentistry of New Jersey, Newark 07103.
Abstract:
The present studies establish that there are specific, significant decreases in the neuronal calcium-binding protein (28-kDa calbindin-D) gene expression in aging and in neurodegenerative diseases. The specificity of the changes observed in calbindin mRNA levels was tested by reprobing blots with calmodulin, cyclophilin, and B-actin cDNAs. Gross brain regions of the aging rat exhibited specific, significant decreases (60-80%) in calbindin mRNA and protein levels in the cerebellum, corpus striatum, and brain-stem region but not in the cerebral cortex or hippocampus. Discrete areas of the aging human brain exhibited significant decreases (50-88%) in calbindin protein and mRNA in the cerebellum, corpus striatum, and nucleus basalis but not in the neocortex, hippocampus, amygdala, locus ceruleus, or nucleus raphe dorsalis. Comparison of diseased human brain tissue with age- and sex-matched controls yielded significant decreases (60-88%) in calbindin protein and mRNA in the substantia nigra (Parkinson disease), in the corpus striatum (Huntington disease), in the nucleus basalis (Alzheimer disease), and in the hippocampus and nucleus raphe dorsalis (Parkinson, Huntington, and Alzheimer diseases) but not in the cerebellum, neocortex, amygdala, or locus ceruleus. Since calbindin gene expression decreased specifically in brain areas known to be particularly affected in aging and in each of the neurodegenerative diseases, these findings suggest that decreased calbindin gene expression may lead to a failure of calcium buffering or intraneuronal calcium homeostasis, which contributes to calcium-mediated cytotoxic events during aging and in the pathogenesis of neurodegenerative diseases.
Insights
Decreased expression of the neuronal calcium-binding protein calbindin-D occurs in aging and neurodegenerative diseases. This reduction may impair calcium buffering, contributing to neuronal damage.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Neuronal calcium homeostasis is crucial for brain function.
- Aging and neurodegenerative diseases are associated with cellular dysfunction.
- Calbindin-D is a key calcium-binding protein in neurons.
Purpose of the Study:
- To investigate changes in calbindin-D gene expression in aging and neurodegenerative conditions.
- To determine if decreased calbindin-D expression contributes to neuronal pathology.
Main Methods:
- Quantitative analysis of calbindin-D mRNA and protein levels in rat and human brain tissue.
- Comparison of gene expression in aging brains versus young controls.
- Analysis of diseased human brain tissue (Parkinson's, Huntington's, Alzheimer's) versus age-matched controls.
Main Results:
- Significant decreases (50-88%) in calbindin-D mRNA and protein were observed in specific brain regions of aging rats and humans.
- Similar reductions were found in the substantia nigra, corpus striatum, nucleus basalis, and hippocampus in patients with Parkinson's, Huntington's, and Alzheimer's diseases.
- Calbindin-D levels remained unchanged in unaffected brain areas.
Conclusions:
- Decreased calbindin-D gene expression is a specific marker of aging and neurodegenerative diseases.
- Reduced calbindin-D may lead to impaired calcium buffering and contribute to calcium-mediated neuronal damage.
- These findings highlight the role of calbindin-D in maintaining neuronal health and its dysregulation in disease pathogenesis.
