Interference of neuronal activity-mediated gene expression through serum response factor deletion enhances mortality and hyperactivity after traumatic brain injury.

07:00 EST 12th January 2020 | BioPortfolio

Summary of "Interference of neuronal activity-mediated gene expression through serum response factor deletion enhances mortality and hyperactivity after traumatic brain injury."

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.


Journal Details

This article was published in the following journal.

Name: FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860


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Medical and Biotech [MESH] Definitions

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.

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