Dynamic mechanical stretch of organotypic brain slice cultures induces differential genomic expression: relationship to mechanical parameters.
Although the material properties of biological tissues are reasonably well established, recent studies have suggested that the biological response of brain tissue and its constituent cells may also be viscoelastic and sensitive to both the magnitude and rate of a mechanical stimulus. Given the potential involvement of changes in gene expression in the pathogenic sequelae after head trauma, we analyzed the expression of 22 genes related to cell death and survival and found that a number of these genes were differentially regulated after mechanical stretch of an organotypic brain slice culture. Twenty-four hours after stretch, the expression of BDNF, NGF, and TrkA was significantly increased, whereas that of bcl-2, CREB, and GAD65 was significantly decreased (MANOVA followed by ANOVA, p < 0.05). Expression of CREB and GAD65 was negatively correlated with strain, whereas expression of APP695 was negatively correlated with strain rate (all p < 0.05). This study demonstrates that a subset of genes involved in cell death and survival are differentially regulated after dynamic stretch in vitro and that the expression of specific genes is correlated with mechanical parameters of that stretch.
Department of Neurosurgery, University of Pennsylvania, Philadelphia 19104, USA.
B
B
Morrison
D F
DF
Meaney
S S
SS
Margulies
T K
TK
McIntosh
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001921:Brain / Q000166:cytology*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D020170:Caspase 1 / Q000235:genetics; D053148:Caspase 3; D020169:Caspases / Q000235:genetics; D002470:Cell Survival / Q000235:genetics*; D002478:Cells, Cultured / Q000502:physiology*; D004548:Elasticity; D005786:Gene Expression Regulation / Q000502:physiology*; D019254:Genes, bcl-2 / Q000235:genetics; D007375:Interleukin-1 / Q000235:genetics; D020932:Nerve Growth Factor / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D014783:Viscosity
D019208:Brain-Derived Neurotrophic Factor; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D020932:Nerve Growth Factor; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D020170:Caspase 1