Abstract
Background: Oxidative stress (OS) is an important factor in brain aging and neurodegenerative diseases. Certain neurons in different brain regions exhibit selective vulnerability to OS. Currently little is known about the underlying mechanisms of this selective neuronal vulnerability. The purpose of this study was to identify endogenous factors that predispose vulnerable neurons to OS by employing genomic and biochemical approaches. Results: In this report, using in vitro neuronal cultures, ex vivo organotypic brain slice cultures and acute brain slice preparations, we established that cerebellar granule (CbG) and hippocampal CA1 neurons were significantly more sensitive to OS (induced by paraquat) than cerebral cortical and hippocampal CA3 neurons. To probe for intrinsic differences between in vivo vulnerable (CA1 and CbG) and resistant (CA3 and cerebral cortex) neurons under basal conditions, these neurons were collected by laser capture microdissection from freshly excised brain sections (no OS treatment), and then subjected to oligonucleotide microarray analysis. GeneChip-based transcriptomic analyses revealed that vulnerable neurons had higher expression of genes related to stress and immune response, and lower expression of energy generation and signal transduction genes in comparison with resistant neurons. Subsequent targeted biochemical analyses confirmed the lower energy levels (in the form of ATP) in primary CbG neurons compared with cortical neurons. Conclusion: Low energy reserves and high intrinsic stress levels are two underlying factors for neuronal selective vulnerability to OS. These mechanisms can be targeted in the future for the protection of vulnerable neurons.
Original language | English (US) |
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Article number | 12 |
Journal | BMC Neuroscience |
Volume | 10 |
DOIs | |
State | Published - Feb 19 2009 |
Funding
This work was supported by grants from the U.S. National Institute on Aging (NIA) AG12993 and AG025350, the U.S. National Institute of Child Health and Human Development (NICHD) HD02528, the U.S. National Center for Research Resources (NCRR) RR-P20 17708, the Kansas Technology Enterprise Corporation, and the Miller-Hadwiger Fund.
ASJC Scopus subject areas
- General Neuroscience
- Cellular and Molecular Neuroscience