Genomic and biochemical approaches in the discovery of mechanisms for selective neuronal vulnerability to oxidative stress

doi:10.1186/1471-2202-10-12

BMC Neuroscience

Volume 10

Viewing options:

Abstract
Full text
PDF (2.2MB)
Additional files

Associated material:

Related literature:

Articles citing this article
on Google Scholar
on ISI Web of Science
on PubMed Central
Other articles by authors
on Google Scholar

Wang X
Zaidi A
Pal R
Garrett AS
Braceras R
Chen X
Michaelis ML
Michaelis EK

on PubMed

Wang X
Zaidi A
Pal R
Garrett AS
Braceras R
Chen X
Michaelis ML
Michaelis EK
Related articles/pages
on Google

on Google Scholar

on PubMed

Tools:

Nominate for award

Post to:

Research article

Genomic and biochemical approaches in the discovery of mechanisms for selective neuronal vulnerability to oxidative stress

Xinkun Wang¹^,2 , Asma Zaidi²^,3 , Ranu Pal¹^,2 , Alexander S Garrett⁴^,5 , Rogelio Braceras²^,6 , Xue-wen Chen⁴ , Mary L Michaelis¹^,2 and Elias K Michaelis¹^,2

¹Higuchi Biosciences Center, 2099 Constant Ave., University of Kansas, Lawrence, KS 66047, USA

²Department of Pharmacology and Toxicology, 1251 Wescoe Dr., University of Kansas, Lawrence, KS 66045, USA

³Current address: Department of Biochemistry, 1750 Independence Ave., Kansas City University of Medicine and Biosciences, Kansas City, MO 64106, USA

⁴Bioinformatics and Computational Life Sciences Laboratory, Department of Electrical Engineering and Computer Science, 2335 Irving Hill Rd., University of Kansas, Lawrence, KS 66045, USA

⁵Current address: Stowers Institute for Medical Research, 1000 E 50th St., Kansas City, MO 64110, USA

⁶Current address: Daiichi Sankyo Inc., Two Hilton Court, Parsippany, NJ 07054, USA

author email corresponding author email

BMC Neuroscience 2009, 10:12doi:10.1186/1471-2202-10-12


Published:	19 February 2009

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.