Using Oligo Array Analysis to Determine Genes of Importance in the Meninges and Associated Vasculature Function and their Sensitivity to Amphetamine Toxicity

ABSTRACT: Oligo array analysis with bioinformatics tools identified genes with very high expression levels in the meninges, arachnoid and pial membranes, and associated vasculature (MAV) as potentially important and unique to these tissues in rat. It was also determined whether these genes were more sensitive to expression changes after a neurotoxic exposure to amphetamine (AMPH). Gene expression in the vascular rich MAV was compared to the neuronal rich tissues of the striatum and parietal cortex. In controls, 850 genes differed by more than 5-fold when comparing the MAV to both striatum and parietal cortex. Genes specifically identified with the blood-brain barrier (BBB) were also expressed at high levels indicating they may help form tight junctions in MAV. Genes with 15-fold or greater expression in MAV compared to striatum or cortex are of potential uniqueness and importance to MAV function. Many of the identified genes are abundant in different types of epithelial tissue and function in binding, transport or metabolize ions and solute, and may help MAV regulate cerebrospinal fluid. Many others with high expressions are involved in immune system function possibly serving to facilitate lymphocyte and macrophage trafficking in vasculature and cerebrospinal fluid. Expression in the MAV has similarities to the choroid plexus indicating considerable overlap in functions. Genes in MAV with a higher expression (relative to brain) were affected in greater numbers than expected by EIH and AMPH (SIGNIFICANT?). Many expression increases evoked by AMPH and EIH in MAV relate to reactive oxidative stress and inflammation. However, AMPH induced more robust alterations in the expression of genes related to ion/solute transport, lipid metabolism, bacterial infection and damage than EIH. The BBB-related genes Sox18 and Cldn5 expression decreased more with AMPH than EIH, and Cldn 9 and Esam were increase only by AMPH. It is not known how these changes affect BBB function and integrity. Gene expression patterns in MAV were compared to two regions of brain (striatum and parietal cortex) to identify genes important to MAV function and determine whether their expressions were sensitive to a neurotoxic exposure to amphetamine.

ORGANISM(S): Rattus norvegicus

SUBMITTER: John Bowyer 

PROVIDER: E-GEOD-23093 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress