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Genome-wide DNA Microarray Analysis Unravels Rapid Changes in the Transcriptome of MK-801 treated Rat Brain

ABSTRACT: N-Methyl-D-aspartate receptors (NMDAr), widely located around the central nervous system, are known to be involved in behavioral disorders. Dizocilpine (commonly referred to as MK-801) is a well known non-competitive NMDAr antagonist. We treated rats with intraperitoneal injection [0.08 (low-dose) and 0.16 (high-dose) mg/kg] of MK-801. In one experiment, 40 min after NaCl (vehicle control) and MK-801 (0.08 mg/kg) injection, electrocorticogram (ECoG) signals were analyzed. In the second experiment, 40 min post-injection, the whole brain of each animal was rapidly removed and separated into amyglada, cerebral cortex, hippocampus, hypothalamus, midbrain and ventral striatum) on ice, followed by analysis using a 4x44K DNA microarray chip. Spectral analysis revealed that a single systemic injection of MK-801 significantly and selectively augmented the power of baseline (30-80 Hz) frequency oscillations. DNA microarray analysis showed the largest number (up- and down- regulations) of gene expressions in the cerebral cortex (378), midbrain (376), hippocampus (375), ventral striatum (353), amygdala (301), and hypothalamus (201) under low-dose of MK-801. Under high-dose, ventral striatum (811) showed the largest number of gene expression changes. Gene expression changes were functionally categorized to reveal expression of genes and function varies with each brain region. MK-801 increases the synchrony of baseline oscillations, causing very early changes in gene expressions in rat brain after acute MK-801 treatment, a first report.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE63639 | GEO | 2014/11/26

SECONDARY ACCESSION(S): PRJNA268513

REPOSITORIES: GEO

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Project description:N-Methyl-D-aspartate receptors (NMDAr), widely located around the central nervous system, are known to be involved in behavioral disorders. Dizocilpine (commonly referred to as MK-801) is a well known non-competitive NMDAr antagonist. We treated rats with intraperitoneal injection [0.08 (low-dose) and 0.16 (high-dose) mg/kg] of MK-801. In one experiment, 40 min after NaCl (vehicle control) and MK-801 (0.08 mg/kg) injection, electrocorticogram (ECoG) signals were analyzed. In the second experiment, 40 min post-injection, the whole brain of each animal was rapidly removed and separated into amyglada, cerebral cortex, hippocampus, hypothalamus, midbrain and ventral striatum) on ice, followed by analysis using a 4x44K DNA microarray chip. Spectral analysis revealed that a single systemic injection of MK-801 significantly and selectively augmented the power of baseline (30-80 Hz) frequency oscillations. DNA microarray analysis showed the largest number (up- and down- regulations) of gene expressions in the cerebral cortex (378), midbrain (376), hippocampus (375), ventral striatum (353), amygdala (301), and hypothalamus (201) under low-dose of MK-801. Under high-dose, ventral striatum (811) showed the largest number of gene expression changes. Gene expression changes were functionally categorized to reveal expression of genes and function varies with each brain region. MK-801 increases the synchrony of baseline oscillations, causing very early changes in gene expressions in rat brain after acute MK-801 treatment, a first report. The overall goal of the present study was to identify gene expression patterns along rat chromosomes in different brain regions after a single injection of MK-801, which exerts a longer acute effect than ketamine on ongoing brain activities. Two approaches were taken, first electrophysiological and send molecular analysis, where the brain of MK-801-treated rats was subjected to a genome-wide transcriptome mapping analysis (~4400 genes) in the cerebral cortex, midbrain, hippocampus, ventral striatum, amygdala, and hypothalamus regions.

Project description:Background: N-Methyl-D-aspartate receptors (NMDAr), widely located around the central nervous system, are known to be involved in behavioral disorders. Dizocilpine (commonly referred to as MK-801) is a well known non-competitive NMDAr antagonist. Methods: We treated rats with intraperitoneal injection [0.08 (low-dose) and 0.16 (high-dose) mg/kg] of MK-801. In one experiment, 40 min after NaCl (vehicle control) and MK-801 (0.08 mg/kg) injection, electrocorticogram (ECoG) signals were analyzed. In the second experiment, 40 min post-injection, the whole brain of each animal was rapidly removed and separated into amyglada, cerebral cortex, hippocampus, hypothalamus, midbrain and ventral striatum) on ice, followed by analysis using a 4x44K DNA microarray chip. Results: Spectral analysis revealed that a single subcutaneous injection of MK-801 significantly and selectively augmented the power of spontaneous gamma and higher-frequency oscillations. The results from DNA microarray analysis of 4400 genes showed the largest number (up- and down- regulations) of gene expressions in the cerebral cortex (378), midbrain (376), hippocampus (375), ventral striatum (353), amygdala (301), and hypothalamus (201) under low-dose of MK-801. Under high-dose, ventral striatum (811) showed the largest number of gene expression changes. These genes represented... Conclusions: Our results reveal that MK-801 triggered i) an increase in the power of gamma oscillations, and ii) simultaneously caused very early changes in gene expressions in the rat brain, representing a first such inventory of gene expression profiles in brain after acute MK-801 treatment. Nine male 10-weeks-old Wistar rats (300-350 g BW) were housed in acrylic cages (3/cage) at 24ÂºC and given access to tap water and laboratory chow ad libitum. The rats were divided into two groups, and each group rats received i.p. injection of 0.08 (low-dose) and 0.16 (high-dose) mg/kg of MK-801, respectively. Three rats were treated with saline as sham (vehicle control group) using the same method. After 40 min post-injection, the whole brain of each animal was rapidly removed and put on ice, and brain regions were separated according to the method of Glowinski and Iversen (1996), with minor modifications (Hirano et al., 2007). Each brain region was placed in a 2 mL Eppendorf tube, quickly immersed in liquid nitrogen before being stored in -80ÂºC prior to further analysis. Each sample was immediately weighed, flash-frozen in liquid nitrogen and stored at -80ÂºC prior to further analysis. A rat 4 x 44K whole genome oligo DNA microarray chip (G4131F, Agilent Technologies, Palo Alto, CA, USA) was used for global gene expression analysis. The effects of MK-801 were examined in the 6 brain reagion, Ventral striatum, Cerebral cortex, Midbrain, Amygdala, Hippocampus, and Hypothalamus.

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Genome-wide DNA Microarray Analysis Unravels Rapid Changes in the Transcriptome of MK-801 treated Rat Brain

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