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Traumatic brain injury (TBI) is one of the most frequent causes of brain injury and mortality in young adults with detrimental sequelae such as cognitive impairments, epilepsy, and attention-deficit hyperactivity disorder. TBI modulates the neuronal excitability resulting in propagation of a neuronal activity-driven gene expression program. However, the impact of such neuronal activity mediated gene expression in TBI has been poorly studied. In this study we analyzed mouse mutants of the prototypical neuronal activity-dependent transcription factor SRF (serum response factor) in a weight-drop TBI model. Neuron-restricted SRF deletion elevated TBI inflicted mortality suggesting a neuroprotective SRF function during TBI. Behavioral inspection uncovered elevated locomotor activity in Srf mutant mice after TBI in contrast to hypoactivity observed in wild-type littermates. This indicates an SRF role in modulation of TBI-associated alterations in locomotor activity. Finally, induction of a neuronal activity induced gene expression program composed of immediate early genes (IEGs) such as Egr1, Egr2, Egr3, Npas4, Atf3, Arc, Ptgs2, and neuronal pentraxins (Nptx2) was compromised upon SRF depletion. Overall, our data show a role of neuronal activity-mediated gene transcription during TBI and suggest a molecular link between TBI and such post-TBI neurological comorbidities involving hyperactivity phenotypes.
This article was published in the following journal.
Name: FASEB journal : official publication of the Federation of American Societies for Experimental Biology
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The artificial induction of GENE SILENCING by the use of RNA INTERFERENCE to reduce the expression of a specific gene. It includes the use of DOUBLE-STRANDED RNA, such as SMALL INTERFERING RNA and RNA containing HAIRPIN LOOP SEQUENCE, and ANTI-SENSE OLIGONUCLEOTIDES.
The use of techniques that produce a functional MUTATION or an effect on GENE EXPRESSION of a specific gene of interest in order to identify the role or activity of the gene product of that gene.
The introduction of functional (usually cloned) GENES into cells. A variety of techniques and naturally occurring processes are used for the gene transfer such as cell hybridization, LIPOSOMES or microcell-mediated gene transfer, ELECTROPORATION, chromosome-mediated gene transfer, TRANSFECTION, and GENETIC TRANSDUCTION. Gene transfer may result in genetically transformed cells and individual organisms.
The expression of a gene in an abnormal place, or at an abnormal time in an organism. Ectopic Gene Expression is often induced artificially by genetic techniques.
A form of gene interaction whereby the expression of one gene interferes with or masks the expression of a different gene or genes. Genes whose expression interferes with or masks the effects of other genes are said to be epistatic to the effected genes. Genes whose expression is affected (blocked or masked) are hypostatic to the interfering genes.
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