title: Contrasting the effects of proton irradiation on dendritic complexity of subiculum neurons in wild type and MCAT mice.
abstract: Growing evidence suggests that radiation-induced oxidative stress directly affects a wide range of biological changes with an overall negative impact on CNS function. In the past we have demonstrated that transgenic mice over-expressing human catalase targeted to the mitochondria (MCAT) exhibit a range of neuroprotective phenotypes following irradiation that include improved neurogenesis, dendritic complexity, and cognition. To determine the extent of the neuroprotective phenotype afforded by MCAT expression in different hippocampal regions, we analyzed subiculum neurons for changes in neuronal structure and synaptic integrity after exposure to low dose (0.5 Gy) 150 MeV proton irradiation. One month following irradiation of WT and MCAT mice, a range of morphometric parameters were quantified along Golgi-Cox impregnated neurons. Compared with WT mice, subiculum neurons from MCAT mice exhibited increased trends (albeit not statistically significant) toward increased dendritic complexity in both control and irradiated cohorts. However, Sholl analysis of MCAT mice revealed significantly increased arborization of the distal dendritic tree, indicating a protective effect on secondary and tertiary branching. Interestingly, radiation-induced increases in postsynaptic density protein (PSD-95) puncta were not as pronounced in MCAT compared with WT mice, and were significantly lower after the 0.5 Gy dose. As past data has linked radiation exposure to reduced dendritic complexity, elevated PSD-95 and impaired cognition, reductions in mitochondrial oxidative stress have proven useful in ameliorating many of these radiation-induced sequelae. Data presented here shows similar trends, and again points to the potential benefits of reducing oxidative stress in the brain to attenuate radiation injury. Environ. Mol. Mutagen. 57:364-371, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Radiation Oncology, University of California, Irvine, California.
authors.forename: Nicole N
authors.initials: NN
authors.lastname: Chmielewski
authors.affiliation: Department of Radiation Oncology, University of California, Irvine, California.
authors.forename: Chongshan
authors.initials: C
authors.lastname: Caressi
authors.affiliation: Department of Radiation Oncology, University of California, Irvine, California.
authors.forename: Erich
authors.initials: E
authors.lastname: Giedzinski
authors.affiliation: Department of Radiation Oncology, University of California, Irvine, California.
authors.forename: Vipan K
authors.initials: VK
authors.lastname: Parihar
authors.affiliation: Department of Radiation Oncology, University of California, Irvine, California.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Limoli
mesh_terms: D000818:Animals; D002374:Catalase / Q000235:genetics / Q000378:metabolism*; D016371:Cranial Irradiation; D000076122:Disks Large Homolog 4 Protein; D051528:Guanylate Kinases / Q000378:metabolism; D006624:Hippocampus / Q000201:enzymology / Q000378:metabolism / Q000528:radiation effects*; D006801:Humans; D021621:Imaging, Three-Dimensional; D008565:Membrane Proteins / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008928:Mitochondria / Q000201:enzymology / Q000528:radiation effects*; D009473:Neuronal Plasticity / Q000528:radiation effects*; D009474:Neurons / Q000201:enzymology / Q000378:metabolism / Q000528:radiation effects*; D011522:Protons; D011829:Radiation Dosage
chemical_list: D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D008565:Membrane Proteins; D011522:Protons; D002374:Catalase; D051528:Guanylate Kinases
keywords: PSD-95; catalase; dendritic complexity; irradiation; mitochondria; subiculum