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 vasculatures (MAV) which are potentially important and unique to these tissues functional capabilities in rat. It was also determined if these genes were more sensitive to expression changes after a neurotoxic exposure to environmentally induced hyperthermia (EIH) or amphetamine (AMPH). Gene expression in the MAV was compared to the neuronal rich tissues of the striatum and parietal cortex. In controls, 1,116 genes differed by more than 5-fold when comparing 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. The more than 300 genes having a 15-fold or greater expression in MAV compared to striatum and cortex were deemed of potential uniqueness and importance to MAV function. Many of these genes are abundant in different types of epithelial tissue and function in binding, transport or metabolism of 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. Genes in MAV with a higher expression (relative to striatum and cortex) were affected in greater numbers than expected by EIH and AMPH. 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 (Slc15a1), lipid metabolism (Fst), bacterial infection (Lbp) and oddly pancreatitis (Reg3a, Reg3b). Expression of the BBB-related genes Sox18 and Cldn5 decreased in all regions with AMPH and EIH but even more so in MAV. Esam increased with AMPH in all regions while Angpt2 was only affected in striatum and parietal cortex. It is not known how these changes affect MAV, striatum or parietal cortex tight junction function/BBB and integrity.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE23093 | GEO | 2010/08/24

SECONDARY ACCESSION(S): PRJNA131873

REPOSITORIES: GEO