| Abstract No.: | B-C2107 |
| Country: | Canada |
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| Title: | CHANGES IN HIPPOCAMPAL GENE EXPRESSION OF BDNF, TRKB AND GAP-43 INDUCED BY GLOBAL ISCHEMIA MAY BE FURTHER ALTERED BY PROTEIN-ENERGY MALNUTRITION |
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| Authors/Affiliations: | 1 Erin Prosser-Loose*; 2 Valerie Verge; 1 Phyllis Paterson;
1 College of Pharmacy and Nutrition and Cameco Multiple Sclerosis Neuroscience Research Center, University of Saskatchewan; 2 Dept. of Anatomy and Cell Biology and Cameco Multiple Sclerosis Neuroscience Research Center, University of Saskatchewan, SK, Canada
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| Content: | Introduction: Approximately 16% of elderly acute stroke patients are affected by protein-energy malnutrition (PEM) upon admission to hospital. Our laboratory has previously demonstrated that PEM worsens functional outcome in a gerbil model of global ischemia in which the hippocampal CA1 region is selectively damaged. However the mechanisms behind this functional deficit are yet to be determined.
Objectives: The objective of this study is to determine whether PEM alters post-ischemic expression of the plasticity-associated genes, brain-derived neurotrophic factor (BDNF), its receptor tropomyosin-related kinase B (trkB) and growth-associated protein-43 (GAP-43) by examining both mRNA and protein expression in the CA1 region of the hippocampus.
Materials and Methods: Male Mongolian gerbils (11-12wk) were randomized to either modified AIN-93M control diet (12.5% protein) or PEM (2% protein). At 28 days, animals underwent 5min bilateral common carotid artery occlusion or sham surgery. Activity was monitored using infrared beam interruptions for 20h post-surgery to ensure consistency of the ischemic insult based on persistent hyperactivity. Experimental groups consisted of control diet-sham surgery (CON-S), control diet-ischemia (CON-I), PEM-sham surgery (PEM-S) and PEM-ischemia (PEM-I). Animals were perfused at 1, 3 and 7d post-surgery, and brains were processed for in-situ hybridization or immunohistochemistry to detect BDNF, trkB, and GAP-43 mRNA and protein, respectively.
Results: Preliminary results indicate low BDNF protein expression in the CA1 fibres at 1d, followed by increased expression in large non-pyramidal cells at 3 and 7d in both ischemic groups. Protein expression of trkB is present in fibres surrounding the CA1 layer and is low at 1d. This is followed by an increase within the pyramidal cells in both ischemic groups at 3 and 7d that is more pronounced in the PEM-I group at 3d. At 1d, GAP-43 protein expression is present in low levels in the fibres surrounding the CA1 layer. Expression is increased within the pyramidal cells after ischemia at 3 and 7d, and this is exacerbated in the PEM-I group. PEM may also have an independent effect since trkB expression is elevated in the PEM-S group at 3d as is GAP-43 at 3 and 7d. Patterns of protein expression appear to correlate well with the corresponding mRNA expression
Conclusion: These findings confirm previous documented changes in plasticity-associated gene expression following ischemia. PEM, when present at the time of the insult, appears to alter the expression of some of these genes in the CA1 region of the hippocampus. These alterations may contribute to functional deficits and could be detrimental to post-ischemic recovery events. Quantitative temporal analysis is being performed to verify these changes in mRNA and protein levels in the CA1 as well as other regions of the hippocampus.
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