Abstract/Details

Analysis of amphetamine-induced neurotoxicity in the cortices of wild-type and superoxide dismutase transgenic mice


2009 2009

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Abstract (summary)

Amphetamine is an addictive psychostimulant whose chronic abuse can cause impairments in cognitive functions and neurodegenerative changes in the brain. These include loss of dopaminergic axons and death of non-dopaminergic neurons in the striatum. The present study was undertaken to examine the extent to which amphetamine can cause axonal degeneration in the mouse cortex and to assess the potential role of superoxide radicals in mediating the toxic effects of the drug in that brain region. Administration of amphetamine (10 mg/kg, 4 times, 2 h apart) caused significant depletion of dopamine and its metabolite 3, 4-dihydroxyphenylacetic acid in the cortices of wild-type mice. In addition, superoxide dismutase transgenic mice were partially protected against amphetamine-induced toxic effects. Microarray studies conducted to test if amphetamine induced differential gene expression revealed that the same dose of the drug caused changes in the expression of 153 genes in the cortices of wild-type and superoxide dismutase transgenic mice. These genes are involved in several biological processes, such as transcription, translation, signal transduction, mitochondria-related functions, inflammatory response, cell cycle, cell adhesion, cytoskeletal activity, and apoptosis. Among the genes changed, we observed that amphetamine caused a differential expression of immediate early genes c-fos oncogene, junB oncogene, and activity-regulated cytoskeletal proteins, as well as those of dual specificity phosphatase 1, neuronal pentraxin II and caspase1 in a superoxide-dependent fashion. These results suggest that the long-term effects of the drug are dependent, in part, on the generation of reactive superoxides in the mouse cortex.

Indexing (details)


Subject
Neurosciences
Classification
0317: Neurosciences
Identifier / keyword
Biological sciences; Amphetamines; Cortex; Dopamine; Microarray analysis; Neurotoxicity; Superoxide dismutase; Superoxide radicals; Toxicity
Title
Analysis of amphetamine-induced neurotoxicity in the cortices of wild-type and superoxide dismutase transgenic mice
Author
Atianjoh, Fidelis Eghoateh
Number of pages
123
Publication year
2009
Degree date
2009
School code
0088
Source
DAI-B 70/03, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
ISBN
9781109069556
Advisor
Heinbockel, Thomas H.; Wilson, James S.
Committee member
Aziz, Mohammed A.; Baker, James H.; Gatti, Philip J.; Gondre-Lewis, Marjorie C.; Heinbockel, Thomas H.
University/institution
Howard University
Department
Anatomy
University location
United States -- District of Columbia
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
3350067
ProQuest document ID
304895914
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/304895914
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