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Results for “Brain Gene Expression”

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At least 109 records · Page 6Linked to original sources
PubMed2002

Nuclear receptor coactivators modulate hormone-dependent gene expression in brain and female reproductive behavior in rats.

Gonadal steroid hormones act in the brain to elicit changes in gene expression that result in profound effects on behavior and physiology. A variety of in vitro studies indicate that nuclear receptor coactivators are required for efficient transcriptional activity of steroid receptors. Two nuclear receptor coactivators, steroid receptor coactivator-1 (SRC-1) and cAMP response element binding protein-binding protein (CBP), have been shown to act in concert to enhance ER activity in vitro. In the present study, we investigated the function of these important nuclear receptor coactivators in estrogen action in rodent brain. Reduction of SRC-1 and CBP protein in brain disrupted ER-mediated activation of the behaviorally relevant progestin receptor gene. Furthermore, we found that SRC-1 and CBP function in brain to modulate the expression of hormone-dependent female sexual behavior. These findings indicate that these nuclear receptor coactivators function in brain to modulate ER transcriptional activity and the expression of hormone-dependent behavior.

Animals↗
PubMed2004

Angiotensin II AT1 receptor antagonism downregulates stress-related gene expression in brain microvessels from spontaneously hypertensive and normotensive rats.

We studied the effect of treatment with the Angiotensin II AT(1) receptor antagonist candesartan (0.3 mg/kg/day via osmotic minipumps for 4 weeks compared with administration of vehicle) in brain microvessels in adult spontaneously hypertensive rats (SHR) that were vulnerable to stroke and normotensive control rats (WKY). At the dose administered, candesartan normalized blood pressure in SHR without significantly affecting blood pressure in WKY rats. We performed the gene expression analysis in rat brain microvessels using the Affymetrix Gene Chip Expression Analysis Technique. From a total of 8,799 probe array sets analyzed, we found abundant abnormalities in gene expression in SHR. Because stress has been suggested as a precipitant factor in brain ischemia and treatment with AT(1) receptor antagonist candesartan prevents the hormonal and sympathoadrenal reaction to isolation stress and protects from stress-induced gastric ulcers, we focused on the expression of stress-related genes. We found a higher number of probe array sets modified by candesartan treatment in normotensive WKY rats than in hypertensive SHR. AT(1) receptor blockade decreased the transcription levels of the stress-related tyrosine kinase receptor, stathmin, and fibroblast growth receptor genes in WKY and SHR rats. Our results indicate that Angiotensin II and its AT(1) receptors can influence gene expression independently of the effects on blood pressure. In addition, AT(1) receptor regulation of stress-related genes in brain microvessels may explain the proposed association between stress and ischemic disorders of the brain.

Angiotensin II↗
PubMed2006

Mouse LGI3 gene: expression in brain and promoter analysis.

Leucine-rich glioma inactivated 3 (LGI3) is a member of LGI/epitempin family of which the first member, LGI1/epitempin, was shown to be mutated in glioma and autosomal dominant lateral temporal epilepsy. Similar to LGI1, LGI3 is expressed predominantly in brain and its function is unknown. In this study, we examined the expression of mouse LGI3 (mLGI3) in adult and developing brain and analyzed the 5'-upstream transcriptional regulatory regions of mLGI3 gene. In situ hybridization showed that mLGI3 was expressed in widespread areas with selective regional variation in adult brain. In developing brain, mLGI3 mRNA was expressed at low level during embryo stages and markedly increased in broad areas after birth. Analysis of the 5'- and 3'-ends of mLGI3 mRNA identified a single transcription start site and two alternative 3'-ends. Luciferase reporter analysis using Neuro-2a cells and electrophoretic mobility shift assays identified a neuronal restrictive silencer element (NRSE; -2573 approximately -2553) and a phorbol ester-sensitive AP-2 element with repressor activity (-44 approximately -33) among multiple positive and negative regulatory regions. Since NRSE and AP-2 are implicated in neuron-specific gene expression and developmental regulation of many genes in brain, respectively, these results suggested that NRSE and AP-2 might play important roles in regulation of mLGI3 expression in brain.

Animals↗
PubMed2001

A database for regional gene expression in the human brain.

Alterations in gene expression levels have been widely studied for various neurological diseases, but few studies have sought to characterize genome-wide gene expression patterns from various regions of the normal brain. A sensitive method for quantifying transcript levels, Serial Analysis of Gene Expression (SAGE), was used to assay expression levels in white matter, thalamus, and cerebellum from the same normal brain, obtained by rapid autopsy. The complete dataset for these SAGE libraries are posted on the Cancer Genome Anatomy Project sponsored SAGEmap website where library comparisons can be made, or the data downloaded for local analysis. The expression of several region-specific genes--neurogenic differentiation 1 (cerebellum), cocaine- and amphetamine-regulated transcript (thalamus), and neurogranin (white matter)--was confirmed using quantitative fluorescent real-time RT-PCR. Further informatics analysis of the data yielded a list of brain-specific genes. The database formed by this analysis provides a means to investigate the expression status of genes involved in the region specific functions of the normal brain. These normal brain gene expression levels also are useful for comparison to pathological expression levels and a sensitive means to determine gene expression in a normal adult brain prior to formulating therapeutic strategies.

Journal Article↗
PubMed1998

Brain-specific gene expression by immortalized microglial cell-mediated gene transfer in the mammalian brain.

The intra-arterial injection of immortalized microglia transfected with the lacZ gene, resulted in the expression of beta-galactosidase in the rat brain at 48 h and the activity of -galactosidase was detected for up to 3 weeks post-injection. More than 30-fold higher activity of beta-galactosidase was detected in the brain than in the liver, lung or spleen at 48 h post-injection. This method allows us to easily deliver the gene of interest to the brain without influencing other organs. Our brain-targeting gene delivery system can facilitate gene therapy of several brain disorders, including brain tumor, metabolic disorders, and degenerative disorders, as well as investigation into the roles of particular genes in brain function and development.

Animals↗
PubMed2004

Identification of differentially expressed genes in scrapie-infected mouse brains by using global gene expression technology.

The pathogenesis of prion diseases, a class of transmissible fatal neurodegenerative diseases in humans and animals, is still unclear. The aim of this study was to identify the differentially regulated genes that correlate with the development of prion diseases for a better understanding of their pathological mechanisms. We employed Affymetrix Mouse Expression Arrays 430A containing >22,000 transcripts and compared the global gene expression profiles from brains of mice who were intracerebrally inoculated with scrapie strains ME7 and RML with those from brains of uninfected and mock-infected mice. The microarray data were analyzed by Significance Analysis of Microarrays, revealing 121 genes whose expression increased at least twofold in both ME7- and RML-infected mouse brains, with an estimated false discovery rate of < or =5%. These genes encode proteins involved in proteolysis, protease inhibition, cell growth and maintenance, the immune response, signal transduction, cell adhesion, and molecular metabolism. The time course of expression generally showed up-regulation of these genes from 120 days postinoculation (dpi) for ME7-inoculated mouse brains and from 90 dpi for RML-inoculated mouse brains. The onset of elevated expression correlated temporally with the onset of PrP(Sc) accumulation and the activation of glia, which may have contributed to neuronal cell death. Among the differentially regulated genes reported in the present study, the emergence of genes for several cathepsins and S100 calcium binding proteins was conspicuous. These and other genes reported here may represent novel potential diagnostic and therapeutic targets for prion disease.

Animals↗
PubMed2001

Ethanol and gene expression in brain.

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Izuru Matusmoto and Peter A. Wilce. The presentations were (1) GABA receptor subunit expression in the human alcoholic brain, by Tracey Buckley and Peter Dodd; (2) NMDAR gene expression during ethanol addiction, by Jorg Puzke, Rainer Spanagel, Walther Zieglgansberger, and Gerald Wolf; (3) Differentially expressed gene in the nucleus accumbens from ethanol-administered rat, by Shuangying Leng; (4) Expression of a novel gene in the alcoholic brain, by Peter A. Wilce; and (5) Investigations of haplotypes of the dopamine D2-receptor gene in alcoholics, by Hans Rommelspacher, Ulrich Finckh, and Lutz G. Schmidt.

Alcoholism↗
PubMed2003

Gene expression in brain: a window on ethanol dependence, neuroadaptation, and preference.

This article represents the proceedings of a symposium at the 2002 joint RSA/ISBRA Conference in San Francisco, California. The organizer was Paula L. Hoffman and the co-chairs were Paula L. Hoffman and Michael Miles. The presentations were (1) Introduction and overview of the use of DNA microarrays, by Michael Miles; (2) DNA microarray analysis of gene expression in brains of P and NP rats, by Howard J. Edenberg; (3) Gene expression patterns in brain regions of AA and ANA rats, by Wolfgang Sommer; (4) Patterns of gene expression in brains of selected lines of mice that differ in ethanol tolerance, by Boris Tabakoff; (5) Gene expression profiling related to initial sensitivity and tolerance in gamma-protein kinase C mutants, by Jeanne Wehner; and (6) Gene expression patterns in human alcoholic brain: from microarrays to protein profiles, by Joanne Lewohl.

Alcohol Drinking↗
PubMed1990

Neuropeptide gene expression in brain is differentially regulated by midbrain dopamine neurons.

In situ hybridization was used to study the expression of prepro-neuropeptide Y (NPY), preprosomatostatin (SOM), preprotachykinin (PPT) and preprocholecystokinin (CCK) mRNA in caudate-putamen and frontoparietal cortex of rat brain with unilateral lesion of midbrain dopamine neurons. Neurons expressing NPY and SOM mRNA showed a similar distribution and the expression of both NPY and SOM appears to be regulated by dopamine in a similar fashion. Following a dopamine deafferentation, the numerical density of both NPY and SOM mRNA producing neurons almost doubled in the lesioned caudate-putamen with no change in the average grain density over positive neurons. Hence, in the intact caudate-putamen dopamine appears to suppress expression of these two neuropeptide genes leading to an activation of both NPY and SOM mRNA expression in many non- or low-expressing neurons when the level of dopamine is decreased. In the fronto-parietal cortex, on the other hand, dopamine appears to stimulate NPY and SOM gene expression. Thus, in the absence of dopamine about half of the NPY positive neurons disappeared. However, for SOM the number of positive neurons did not change, but rather most positive neurons appeared to have down-regulated their SOM mRNA expression. No evidence was found for a change in CCK mRNA expression by the dopamine deafferentation, while PPT mRNA expression decreased in the deafferented caudate-putamen. Consequently, dopamine exerts dissimilar effects on the expression of different neuropeptide genes, that in turn do not respond in the same way in different brain regions.

Animals↗
PubMed2002

Upregulation of chemokine receptor gene expression in brains of Borna disease virus (BDV)-infected rats in the absence and presence of inflammation.

Infection of adult rats with Borna disease virus (BDV) causes CD8 T cell-mediated meningoencephalitis. Previously, we described a complex pattern of chemokine gene expression in the central nervous system (CNS) of such rats. We now found that expression of chemokine receptor genes CXCR3, CCR5, CX(3)CR1, and CXCR4 was also upregulated, which is in agreement with the predominance in brains of adult infected rats of T cells and monocytes/macrophages that express these receptors. In contrast to these rats, neonatally infected rats (designated PTI-NB) develop a persistent CNS infection associated with neurodegenerative processes in the absence of inflammation. In brains of PTI-NB rats, sustained expression of chemokines also takes place. We therefore analyzed mRNA expression of selected chemokine receptor genes, as well as of the chemokine fractalkine in brains of PTI-NB rats. We observed a marked increase of CCR5 and CX(3)CR1 transcripts in brains of these rats. CX(3)CR1 expressing cells were predominantly microglia, and upregulation of CX(3)CR1 was mainly due to an increase in the number of CX(3)CR1 expressing microglia. Fractalkine gene expression was found to be reduced to similar extents in brains of adult and newborn infected rats. These findings might be of relevance with respect to the selective neuronal cell loss observed in brains of PTI-NB rats.

Age Factors↗
PubMed2001

Stroke induces widespread changes of gene expression for glial cell line-derived neurotrophic factor family receptors in the adult rat brain.

Gene expression for glial cell line-derived neurotrophic factor (GDNF) family ligands and receptors was analyzed with in situ hybridization after two focal ischemic insults of different severities. Focal ischemia was induced in rats by either 30 min or 2 h of middle cerebral artery occlusion (MCAO), causing damage to the striatum only, or involving also the parietal cortex, respectively. We found modest, transient elevation of GDNF mRNA in the dentate granule cell layer. In addition, the number of GDNF mRNA-expressing cells increased in the cortex and striatum after 2 h or 30 min of MCAO, respectively. No changes of neurturin or persephin mRNA expression were detected. Both c-Ret and GFRalpha1 mRNA levels were markedly increased in the ipsilateral cortex outside the ischemic lesion at 6-24 h after the 2-h insult, whereas GFRalpha2 expression was decreased in cortical areas both within and outside the lesion. Similar increases of c-Ret and GFRalpha1 mRNA levels were detected in the striatum, and to a lesser extent, in the cortex following 30 min of MCAO. The 2-h insult also gave rise to transient increases of c-Ret and GFRalpha1 mRNA in hippocampal subregions. Thirty minutes and 2 h of MCAO lead to elevated c-Ret, and GFRalpha1 or GFRalpha2 mRNA expression, respectively, in the ipsilateral ventroposterolateral thalamic nucleus. Both insults induced increased levels of GFRalpha1 mRNA in the subventricular zone of the lateral ventricle. Our data indicate major changes of GDNF family signaling in the forebrain, regulated mainly through altered receptor levels, in the post-ischemic phase. These changes could enhance neuroprotective and neuroregenerative responses both to endogenous and exogenous GDNF ligands.

Animals↗
PubMed2004

Gender-specific gene expression in post-mortem human brain: localization to sex chromosomes.

Gender differences in brain development and in the prevalence of neuropsychiatric disorders such as depression have been reported. Gender differences in human brain might be related to patterns of gene expression. Microarray technology is one useful method for investigation of gene expression in brain. We investigated gene expression, cell types, and regional expression patterns of differentially expressed sex chromosome genes in brain. We profiled gene expression in male and female dorsolateral prefrontal cortex, anterior cingulate cortex, and cerebellum using the Affymetrix oligonucleotide microarray platform. Differentially expressed genes between males and females on the Y chromosome (DBY, SMCY, UTY, RPS4Y, and USP9Y) and X chromosome (XIST) were confirmed using real-time PCR measurements. In situ hybridization confirmed the differential expression of gender-specific genes and neuronal expression of XIST, RPS4Y, SMCY, and UTY in three brain regions examined. The XIST gene, which silences gene expression on regions of the X chromosome, is expressed in a subset of neurons. Since a subset of neurons express gender-specific genes, neural subpopulations may exhibit a subtle sexual dimorphism at the level of differences in gene regulation and function. The distinctive pattern of neuronal expression of XIST, RPS4Y, SMCY, and UTY and other sex chromosome genes in neuronal subpopulations may possibly contribute to gender differences in prevalence noted for some neuropsychiatric disorders. Studies of the protein expression of these sex-chromosome-linked genes in brain tissue are required to address the functional consequences of the observed gene expression differences.

Actins↗
PubMed1997

[Specific regulation of gene expression in brain by antisense oligodeoxynucleotides].

The synthetic oligodeoxynucleotide (ODN) complementary to the normal (sense) mRNA, so-called antisense ODN, has been used to regulate the gene expression in the brain. It has been reported to interfere with transcription, pre-mRNA splicing and translation through at least two mechanisms; i.e., its competition with transcription and protein synthesis machinery or induction of mRNA cleavage. The unmodified antisense ODN was shown to be the RNase activator when it hybridizes with at least four contiguous bases of mRNA. In contrast, the phosphorothioate ODN (S-ODN) is reported to be a less effective activator of RNas II and more resistant to the nuclease attack than unmodified ODN. Because of these properties, S-ODNs are preferentially employed in antisense ODN experiments. When the DNA sequence of the target gene is determined, we can design an antisense ODN that selectively hybridizes with the bases of a nucleic acid (DNA or RNA) related to the target gene. The initial sites of specific binding of most drugs are known to be proteins such as receptors and enzymes. Therefore, the specific modulation of target protein synthesis by the antisense ODN method is quite interesting to the pharmacologist. We have studied the change in the morphine-induced behaviors after the microinjection of antisense S-ODN directed against the m-opioid receptor (MOR) into the periaqueductal gray (PAG) or lateral ventricle of rat brain. We could detect the decrease of the MOR mRNA level in PAG by the RT-PCR method and that in whole brain by the Northern blot technique. Although the antisense ODN method seems to be quite useful for the modulation of a given gene expression, many problems still remain to be elucidated. These include the mechanism of the regulation of a target gene, pharmacokinetics of antisense ODN and toxicity of antisense ODN.

Animals↗
PubMed2006

High throughput protein expression screening in the nervous system--needs and limitations.

The cellular complexity of the brain (some estimate that there are up to 10(3) different cell types) is exceeded by the synaptic complexity, with each of the approximately 10(11) neurons in the brain having around 10(3)-10(4) synapses. Proteomic studies of the synapse have revealed that the postsynaptic density is the most complex multiprotein structure yet identified, with approximately 10(3) different proteins. Such studies, however, use brain tissue with many different regions and therefore different cell types, and there is clear potential for heterogeneity of protein content at different synapses within and between brain regions. Although large-scale mRNA-based assays are in progress to map this sort of complexity at the cellular level, and indeed all brain-expressed genes, analysis of protein distribution (at synapses and other structures) is still in the very early stages. We review existing large-scale protein expression studies and the specific technical obstacles that need to be overcome before applying the scaling used in nucleic acid based approaches.

Animals↗
PubMed1995

Characterization of the murine PIG-A promoter region high constitutive PIG-A gene expression in brain.

PIG-A is an X-linked gene that encodes a synthetic element required to initiate glycoinositol phospholipid (GPI) anchor assembly. In this study we characterized genomic sequence flanking the previously identified 5' end of the murine PIG-A gene and analyzed constitutive levels of PIG-A gene expression in vivo in different tissues. We found that the 5'-flanking sequence contains 1) alternative transcriptional start sites at -154 and -34/-33 relative to previously known exon 1 sequence, 2) an MRE and multiple GRE, Ap-2 and Sp-1 consensuses, and 3) a 100-bp-long GC-rich segment bounded by NF-IL6 sites. Our survey of PIG-A mRNA levels in vivo unexpectedly revealed that PIG-A expression levels are 2-4 fold higher in the brain than in other tissues.

Animals↗
PubMed1993

A new family of transcripts of the myelin basic protein gene: expression in brain and in immune system.

A cDNA clone (MBP2) corresponding to a novel mouse myelin basic protein (MBP) mRNA has been isolated from an adult mouse bone marrow cDNA library. It contains the MBP exons 1a-7 except exon 5. Using PCR experiments we have determined that this MBP2 mRNA belongs to a new MBP mRNA family initiated upstream from exon 1b. Their 5' end extends into exon 1a and/or the region 0' previously described. These mRNAs are generated by alternative splicing of the primary transcript involving excision of exon 1a, 1b, 2, 5, or 6. Thus, these new mRNAs are produced from a promoter(s) located upstream from the major promoter 1b. They are expressed in brain (at least from embryonic day 15), in bone marrow, and in other hemolymphopoietic tissues, particularly in macrophage cells. As their expression is not restricted to myelinating cells, the function of these novel MBP mRNAs and putative proteins might not be related to myelination.

Animals↗
PubMed1999

Effect of portacaval anastomosis on glutamine synthetase protein and gene expression in brain, liver and skeletal muscle.

The effects of chronic liver insufficiency resulting from end-to-side portacaval anastomosis (PCA) on glutamine synthetase (GS) activities, protein and gene expression were studied in brain, liver and skeletal muscle of male adult rats. Four weeks following PCA, activities of GS in cerebral cortex and cerebellum were reduced by 32% and 37% (p<0.05) respectively whereas GS activities in muscle were increased by 52% (p<0.05). GS activities in liver were decreased by up to 90% (p<0.01), a finding which undoubtedly reflects the loss of GS-rich perivenous hepatocytes following portal-systemic shunting. Immunoblotting techniques revealed no change in GS protein content of brain regions or muscle but a significant loss in liver of PCA rats. GS mRNA determined by semi-quantitative RT-PCR was also significantly decreased in the livers of PCA rats compared to sham-operated controls. These findings demonstrate that PCA results in a loss of GS gene expression in the liver and that brain does not show a compensatory induction of enzyme activity, rendering it particularly sensitive to increases in ammonia in chronic liver failure. The finding of a post-translational increase of GS in muscle following portacaval shunting suggests that, in chronic liver failure, muscle becomes the major organ responsible for the removal of excess blood-borne ammonia.

Ammonia↗