Comparative analysis of mRNA levels in the frontal cortex and the hippocampus in the basal state and in response to experimental brain injury

Abstract

Damage to the frontal cortex and to the hippocampus, both in terms of cell loss and neuronal dysfunction, is thought to underlie many of the neurological and behavioural consequences of traumatic brain injury (TBI). Several studies have indicated that the hippocampus is particularly susceptible to central nervous system insults, whereas the frontal cortex possesses relatively higher capacities for regeneration and plasticity. It has been postulated that dissimilarities in the gene expression profiles in these structures, both in the normal and the postinjury states, may underlie these differences. In order to explore this issue, mRNA samples taken from the frontal cortex and the hippocampus of uninjured animals were subjected to high-density microarray analysis. The analysis indicated that the mRNA levels of 65 genes were differentially expressed between these two brain regions. Among these, genes involved in intracellular signalling, neurotransmitter release, and genes encoding for channels and receptors were identified. Samples taken from animals injured using controlled cortical impact (a model of TBI) showed altered mRNA levels for 341 frontal cortex genes 24 h following injury. These genes can be broadly classified into one of 12 functional classes: cell cycle, metabolism, reactive oxygen metabolism, inflammation, receptors, channels and transporters, signal transduction, cytoskeleton, membrane proteins, neuropeptides, growth factors, and proteins involved in transcription/translation. The expression profile of these genes is compared to the expression profile of 241 genes in the hippocampus 24 h following cortical impact injury as previously reported by our laboratory. In addition to genes previously reported in the literature, this study found several genes that have not been associated with TBI. The functional implications of changes in the expression of some of these genes are discussed.

The Effect of Progesterone Dose on Gene Expression after Traumatic Brain Injury

“…There have been several studies evaluating the effect of TBI on the time-dependent expression of specific genes (Bazan et al, 1995;Hayes et al, 1995;Marciano et al, 2002) and more recently, using microarray technology, expression of thousands of genes can be measured (Dash et al, 2004;Di Pietro et al, 2010;Natale et al, 2003;Raghavendra Rao et al, 2003;Rall et al, 2003;Truettner et al, 2005). The majority of the these studies evaluated gene expression only up to 24 h post-injury with the exception of that by Natale and associates who used microarray-based technology to evaluate gene expression 4,8,24, and 72 h post-injury (Natale et al, 2003).…”

Analysis of Functional Pathways Altered after Mild Traumatic Brain Injury

“…We compared the present mCCI data with previously published data from our laboratory using a more severe injury level. 53 It is important to note that our previous study employed a different microarray platform and detection chemistry, interrogated only a subset of the genes (*20%) contained on the RatRef-12 Illumina BeadArray, and the cortical tissues analyzed were distal to the injury site. We found that, of the 4429 genes in common on both arrays, moderate-to-severe and mild injury induced a significant change in mRNA expression level of 282 (6.4%) and 152 (3.4%) genes, respectively.…”

Nedd4-WW Domain-Binding Protein 5 (Ndfip1) Is Associated with Neuronal Survival after Acute Cortical Brain Injury

“…The transcriptional drivers behind these processes are being keenly elucidated, assisted by gene profiling studies that enable a large number of genes to be studied simultaneously. Typically, these studies are conducted using postmortem tissue obtained 4 -24 h after TBI and involve probing mRNA against cDNA arrays or gene chips (Rao et al, 1999;Kobori et al, 2002;Natale et al, 2003;Rall et al, 2003;Yoshiya et al, 2003;Keyvani et al, 2004;Di Giovanni et al, 2005). Together, these studies have confirmed that the trauma response is characterized by altered transcription of genes related to inflammation, apoptosis, neurotransmitter release, cell-cycle activation, gliosis, reactive oxygen metabolism, ionic homeostasis, and neurodegeneration.…”