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  • 1
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Rapid macromolecular synthesis is required for the establishment of long-term neuronal plasticity3'4. To identify molecules that are involved in this process, we and others have used differential cloning strategies to identify genes that are rapidly induced in neurons of the hippocampus and cortex ...
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] G-protein-coupled receptors (GPCRs) transduce signals from extracellular transmitters to the inside of the cell by activating G proteins. Mutation and overexpression of these receptors have revealed that they can reach their active state even in the absence of agonist, as a result of a natural ...
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 57 (1991), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Neuronal stimulation can rapidly activate several immediate early genes that code for transcription factors. We have used primary cortical cultures to study the regulation of four of these genes, c-fos, c-jun, jun-B, and zif268. Im-munocytochemical studies with antibodies to Jun-B, c-Jun, and c-Fos demonstrate intense staining in the nuclei of a subset of cortical neurons in mature cultures (21–25 days in vitro) but not young cultures (3–7 days in vitro). To assess whether this immunoreactivity may be induced by spontaneous synaptic activity that develops with a similar profile, we examined the effects of agents that reduce this synaptic activity. Tetrodotoxin or N-methyl-d-aspartate receptor antagonists suppress basal immunoreactivity to Jun-B and c-Fos, but not c-Jun, indicating that the basal level of c-Jun expression is not dependent on electrical activity. Pierotoxin, an agent that increases synaptic excitation indirectly by blocking inhibitory synaptic currents mediated by γ-aminobutyric acidA receptors, markedly increases the percentage of neurons displaying immunoreactivity to c-Fos, c-Jun, Jun-B, and Zif268. Northern analysis suggests that the increases in immunostaining induced by picrotoxin are secondary to a rapid increase in mRNA for these proteins. These findings provide evidence for rapid transcriptional regulation of immediate early genes in cortical neurons by synaptic activity.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Narp is an immediate early gene product that acts extracellularly to cluster AMPA receptors at excitatory synapses. The present study tested the hypothesis that drugs of abuse alter Narp expression and thereby influence AMPA receptor transmission in addiction-related circuits. Immunohistochemical studies demonstrated the existence of Narp-positive cells in hippocampus, prefrontal cortex (PFC) and nucleus accumbens (NAc), with lower levels of staining in the ventral tegmental area (VTA). To study the effects of psychomotor stimulants, Narp levels were quantified by Western blotting and normalized to actin. There were no differences in Narp levels in any brain region between rats treated with repeated saline injections, a single amphetamine injection (5 mg/kg), repeated amphetamine injections (5 mg/kg × 5 days), or repeated cocaine injections (20 mg/kg twice daily × 7 days). We also examined the possible role of Narp in individual differences in responding to a novel environment, a predictor of behavioural responses to psychomotor stimulant drugs including the propensity to acquire drug self-administration. Narp levels in the PFC, but not other regions, were significantly correlated with locomotor activity in a novel environment. These findings suggest that differential Narp expression in the PFC may be involved in determining individual vulnerability to drugs of abuse, perhaps by influencing the activity of its excitatory projections.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Despite an extensive research on the molecular basis of epilepsy, the essential players in the epileptogenic process leading to epilepsy are not known. Gene expression analysis is one strategy to enhance our understanding of the genes contributing to the functional neuronal changes underlying epileptogenesis. In the present study, we used the novel MPSS (massively parallel signature sequencing) method for analysis of gene expression in the rat kindling model of temporal lobe epilepsy. Kindling by repeated electrical stimulation of the amygdala resulted in the differential expression of 264 genes in the hippocampus compared to sham controls. The most strongly induced gene was Homer 1A, an immediate early gene involved in the modulation of glutamate receptor function. The overexpression of Homer 1A in the hippocampus of kindled rats was confirmed by RT-PCR. In order to evaluate the functional implications of Homer 1A overexpression for kindling, we used transgenic mice that permanently overexpress Homer 1A. Immunohistochemical characterization of these mice showed a marked Homer 1A overexpression in glutamatergic neurons of the hippocampus. Kindling of Homer 1A overexpressing mice resulted in a retardation of seizure generalization compared to wild-type controls. The data demonstrate that kindling-induced epileptogenesis leads to a striking overexpression of Homer 1A in the hippocampus, which may represent an intrinsic antiepileptogenic and anticonvulsant mechanism in the course of epileptogenesis that counteracts progression of the disease.
    Type of Medium: Electronic Resource
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