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Research Article

A Drosophila model of closed head traumatic brain injury

Rebeccah J. Katzenberger, Carin A. Loewen, Douglas R. Wassarman, Andrew J. Petersen, Barry Ganetzky, and David A. Wassarman
  1. aDepartment of Cell and Regenerative Biology, School of Medicine and Public Health, and
  2. bLaboratory of Genetics, University of Wisconsin–Madison, Madison, WI 53706

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PNAS first published October 14, 2013; https://doi.org/10.1073/pnas.1316895110
Rebeccah J. Katzenberger
aDepartment of Cell and Regenerative Biology, School of Medicine and Public Health, and
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Carin A. Loewen
bLaboratory of Genetics, University of Wisconsin–Madison, Madison, WI 53706
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Douglas R. Wassarman
aDepartment of Cell and Regenerative Biology, School of Medicine and Public Health, and
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Andrew J. Petersen
aDepartment of Cell and Regenerative Biology, School of Medicine and Public Health, and
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Barry Ganetzky
bLaboratory of Genetics, University of Wisconsin–Madison, Madison, WI 53706
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  • For correspondence: ganetzky@wisc.edu dawassarman@wisc.edu
David A. Wassarman
aDepartment of Cell and Regenerative Biology, School of Medicine and Public Health, and
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  • For correspondence: ganetzky@wisc.edu dawassarman@wisc.edu
  1. Contributed by Barry Ganetzky, September 6, 2013 (sent for review August 6, 2013)

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Significance

Traumatic brain injury (TBI) occurs when a strong jolt to the head causes damage to brain cells, resulting in immediate and long-term consequences including physical, behavioral, and cognitive problems. Despite the importance of TBI as a major health issue, our understanding of the underlying cellular and molecular mechanisms is limited. To unravel these mechanisms, we have developed a model of TBI in the fruit fly, Drosophila melanogaster, where we can apply many powerful experimental tools. The main features of human TBI also occur in flies, suggesting that the underlying mechanisms are conserved. Our studies demonstrate the value of a fly model for understanding the consequences of TBI and may ultimately enable development of therapies for their prevention and treatment.

Abstract

Traumatic brain injury (TBI) is a substantial health issue worldwide, yet the mechanisms responsible for its complex spectrum of pathologies remains largely unknown. To investigate the mechanisms underlying TBI pathologies, we developed a model of TBI in Drosophila melanogaster. The model allows us to take advantage of the wealth of experimental tools available in flies. Closed head TBI was inflicted with a mechanical device that subjects flies to rapid acceleration and deceleration. Similar to humans with TBI, flies with TBI exhibited temporary incapacitation, ataxia, activation of the innate immune response, neurodegeneration, and death. Our data indicate that TBI results in death shortly after a primary injury only if the injury exceeds a certain threshold and that age and genetic background, but not sex, substantially affect this threshold. Furthermore, this threshold also appears to be dependent on the same cellular and molecular mechanisms that control normal longevity. This study demonstrates the potential of flies for providing key insights into human TBI that may ultimately provide unique opportunities for therapeutic intervention.

  • concussion
  • insect
  • chronic traumatic encephalopathy

Footnotes

  • ↵1To whom correspondence may be addressed. E-mail: ganetzky{at}wisc.edu or dawassarman{at}wisc.edu.
  • Author contributions: R.J.K., A.J.P., B.G., and D.A.W. designed research; R.J.K., C.A.L., D.R.W., A.J.P., and D.A.W. performed research; D.A.W. contributed new reagents/analytic tools; R.J.K., C.A.L., B.G., and D.A.W. analyzed data; and R.J.K., C.A.L., B.G., and D.A.W. wrote the paper.

  • The authors declare no conflict of interest.

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1316895110/-/DCSupplemental.

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TBI in flies
Rebeccah J. Katzenberger, Carin A. Loewen, Douglas R. Wassarman, Andrew J. Petersen, Barry Ganetzky, David A. Wassarman
Proceedings of the National Academy of Sciences Oct 2013, 201316895; DOI: 10.1073/pnas.1316895110

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TBI in flies
Rebeccah J. Katzenberger, Carin A. Loewen, Douglas R. Wassarman, Andrew J. Petersen, Barry Ganetzky, David A. Wassarman
Proceedings of the National Academy of Sciences Oct 2013, 201316895; DOI: 10.1073/pnas.1316895110
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