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Analysis of long-term gene expression in neurons of the hippocampal subfields following traumatic brain injury in rats.
Neuroscience. 2005; 131(1):87-97.N

Abstract

After experimental traumatic brain injury (TBI), widespread neuronal loss is progressive and continues in selectively vulnerable brain regions, such as the hippocampus, for months to years after the initial insult. To clarify the molecular mechanisms underlying secondary or delayed cell death in hippocampal neurons after TBI, we compared long-term changes in gene expression in the CA1, CA3 and dentate gyrus (DG) subfields of the rat hippocampus at 24 h and 3, 6, and 12 months after TBI with changes in gene expression in sham-operated rats. We used laser capture microdissection to collect several hundred hippocampal neurons from the CA1, CA3, and DG subfields and linearly amplified the nanogram samples of neuronal RNA with T7 RNA polymerase. Subsequent quantitative analysis of gene expression using ribonuclease protection assay revealed that mRNA expression of the anti-apoptotic gene, Bcl-2, and the chaperone heat shock protein 70 was significantly downregulated at 3, 6 (Bcl-2 only), and 12 months after TBI. Interestingly, the expression of the pro-apoptotic genes caspase-3 and caspase-9 was also significantly decreased at 3, 6 (caspase-9 only), and 12 months after TBI, suggesting that long-term neuronal loss after TBI is not mediated by increased expression of pro-apoptotic genes. The expression of two aging-related genes, p21 and integrin beta3 (ITbeta3), transiently increased 24 h after TBI, returned to baseline levels at 3 months and significantly decreased below sham levels at 12 months (ITbeta3 only). Expression of the gene for the antioxidant glutathione peroxidase-1 also significantly increased 6 months after TBI. These results suggest that decreased levels of neuroprotective genes may contribute to long-term neurodegeneration in animals and human patients after TBI. Conversely, long-term increases in antioxidant gene expression after TBI may be an endogenous neuroprotective response that compensates for the decrease in expression of other neuroprotective genes.

Authors+Show Affiliations

Department of Anesthesiology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0830, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15680694

Citation

Shimamura, M, et al. "Analysis of Long-term Gene Expression in Neurons of the Hippocampal Subfields Following Traumatic Brain Injury in Rats." Neuroscience, vol. 131, no. 1, 2005, pp. 87-97.
Shimamura M, Garcia JM, Prough DS, et al. Analysis of long-term gene expression in neurons of the hippocampal subfields following traumatic brain injury in rats. Neuroscience. 2005;131(1):87-97.
Shimamura, M., Garcia, J. M., Prough, D. S., Dewitt, D. S., Uchida, T., Shah, S. A., Avila, M. A., & Hellmich, H. L. (2005). Analysis of long-term gene expression in neurons of the hippocampal subfields following traumatic brain injury in rats. Neuroscience, 131(1), 87-97.
Shimamura M, et al. Analysis of Long-term Gene Expression in Neurons of the Hippocampal Subfields Following Traumatic Brain Injury in Rats. Neuroscience. 2005;131(1):87-97. PubMed PMID: 15680694.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Analysis of long-term gene expression in neurons of the hippocampal subfields following traumatic brain injury in rats. AU - Shimamura,M, AU - Garcia,J M, AU - Prough,D S, AU - Dewitt,D S, AU - Uchida,T, AU - Shah,S A, AU - Avila,M A A, AU - Hellmich,H L, PY - 2004/10/03/accepted PY - 2005/2/1/pubmed PY - 2005/4/26/medline PY - 2005/2/1/entrez SP - 87 EP - 97 JF - Neuroscience JO - Neuroscience VL - 131 IS - 1 N2 - After experimental traumatic brain injury (TBI), widespread neuronal loss is progressive and continues in selectively vulnerable brain regions, such as the hippocampus, for months to years after the initial insult. To clarify the molecular mechanisms underlying secondary or delayed cell death in hippocampal neurons after TBI, we compared long-term changes in gene expression in the CA1, CA3 and dentate gyrus (DG) subfields of the rat hippocampus at 24 h and 3, 6, and 12 months after TBI with changes in gene expression in sham-operated rats. We used laser capture microdissection to collect several hundred hippocampal neurons from the CA1, CA3, and DG subfields and linearly amplified the nanogram samples of neuronal RNA with T7 RNA polymerase. Subsequent quantitative analysis of gene expression using ribonuclease protection assay revealed that mRNA expression of the anti-apoptotic gene, Bcl-2, and the chaperone heat shock protein 70 was significantly downregulated at 3, 6 (Bcl-2 only), and 12 months after TBI. Interestingly, the expression of the pro-apoptotic genes caspase-3 and caspase-9 was also significantly decreased at 3, 6 (caspase-9 only), and 12 months after TBI, suggesting that long-term neuronal loss after TBI is not mediated by increased expression of pro-apoptotic genes. The expression of two aging-related genes, p21 and integrin beta3 (ITbeta3), transiently increased 24 h after TBI, returned to baseline levels at 3 months and significantly decreased below sham levels at 12 months (ITbeta3 only). Expression of the gene for the antioxidant glutathione peroxidase-1 also significantly increased 6 months after TBI. These results suggest that decreased levels of neuroprotective genes may contribute to long-term neurodegeneration in animals and human patients after TBI. Conversely, long-term increases in antioxidant gene expression after TBI may be an endogenous neuroprotective response that compensates for the decrease in expression of other neuroprotective genes. SN - 0306-4522 UR - https://www.unboundmedicine.com/medline/citation/15680694/Analysis_of_long_term_gene_expression_in_neurons_of_the_hippocampal_subfields_following_traumatic_brain_injury_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(04)00932-7 DB - PRIME DP - Unbound Medicine ER -