title: Targeted overexpression of mitochondrial catalase prevents radiation-induced cognitive dysfunction.
abstract: OBJECTIVE
  Radiation-induced disruption of mitochondrial function can elevate oxidative stress and contribute to the metabolic perturbations believed to compromise the functionality of the central nervous system. To clarify the role of mitochondrial oxidative stress in mediating the adverse effects of radiation in the brain, we analyzed transgenic (mitochondrial catalase [MCAT]) mice that overexpress human catalase localized to the mitochondria.
  
  
  RESULTS
  Compared with wild-type (WT) controls, overexpression of the MCAT transgene significantly decreased cognitive dysfunction after proton irradiation. Significant improvements in behavioral performance found on novel object recognition and object recognition in place tasks were associated with a preservation of neuronal morphology. While the architecture of hippocampal CA1 neurons was significantly compromised in irradiated WT mice, the same neurons in MCAT mice did not exhibit extensive and significant radiation-induced reductions in dendritic complexity. Irradiated neurons from MCAT mice maintained dendritic branching and length compared with WT mice. Protected neuronal morphology in irradiated MCAT mice was also associated with a stabilization of radiation-induced variations in long-term potentiation. Stabilized synaptic activity in MCAT mice coincided with an altered composition of the synaptic AMPA receptor subunits GluR1/2.
  
  
  METHODS
  Our findings provide the first evidence that neurocognitive sequelae associated with radiation exposure can be reduced by overexpression of MCAT, operating through a mechanism involving the preservation of neuronal morphology.
  
  
  CONCLUSIONS
  Our article documents the neuroprotective properties of reducing mitochondrial reactive oxygen species through the targeted overexpression of catalase and how this ameliorates the adverse effects of proton irradiation in the brain.
authors.affiliation: 1 Department of Radiation Oncology, University of California, Irvine , Irvine, California.
authors.forename: Vipan K
authors.initials: VK
authors.lastname: Parihar
authors.forename: Barrett D
authors.initials: BD
authors.lastname: Allen
authors.forename: Katherine K
authors.initials: KK
authors.lastname: Tran
authors.forename: Nicole N
authors.initials: NN
authors.lastname: Chmielewski
authors.forename: Brianna M
authors.initials: BM
authors.lastname: Craver
authors.forename: Vahan
authors.initials: V
authors.lastname: Martirosian
authors.forename: Josh M
authors.initials: JM
authors.lastname: Morganti
authors.forename: Susanna
authors.initials: S
authors.lastname: Rosi
authors.forename: Roman
authors.initials: R
authors.lastname: Vlkolinsky
authors.forename: Munjal M
authors.initials: MM
authors.lastname: Acharya
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Nelson
authors.forename: Antiño R
authors.initials: AR
authors.lastname: Allen
authors.forename: Charles L
authors.initials: CL
authors.lastname: Limoli
mesh_terms: D000818:Animals; D002374:Catalase / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D003072:Cognition Disorders / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism
chemical_list: D002374:Catalase