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Isoform-dependent effects of apoE on doublecortin-positive cells and microtubule-associated protein 2 immunoreactivity following 137Cs irradiation

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Abstract

Previously we found apoE isoform-dependent effects of 137Cs irradiation on cognitive function of female mice 3 months following irradiation. Alterations in the number of immature neurons and in the levels of the dendritic marker microtubule-associated protein 2 (MAP-2) might contribute to the cognitive changes following irradiation. Therefore, in the present study we determined if, following 137Cs irradiation, there are apoE isoform-dependent effects on loss of doublecortin-positive neuroprogenitor cells or MAP-2 immumonoreactivity. In the dentate gyrus, CA1 and CA3 regions of the hippocampus, enthorhinal and sensorimotor cortex, and central and basolateral nuclei of the amygdala of apoE3 female mice, MAP-2 immunoreactivity increased 3 months following 137Cs irradiation. In addition, at 8 h following irradiation, the number of doublecortin-positive cells was higher in apoE3 than apoE2 or apoE4 mice. Together, these data indicate that brains of apoE3 mice respond differently to 137Cs irradiation than those of apoE2 or apoE4 mice.

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References

  • Acevedo S, Tittle S, Raber J (2008a) Transgenic expression of androgen receptors improves spatial memory retention of sham-irradiated and 137Cesium irradiated female mice. Radiat Res 170:161–167

    Google Scholar 

  • Acevedo S, McGinnis G, Raber J (2008b) Effects of 137Cesium irradiation on cognitive performance and measures of anxiety of Apoe-/- and wild-type female mice. Radiat Res 170:168–184

    Google Scholar 

  • Benice T, Rizk A, Pfankuch T, Kohama S, Raber J (2006) Sex-differences in age-related cognitive decline in C57BL/6 J mice associated with increased brain microtubuleassociated protein 2 and synaptophysin immunoreactivity. Neuroscience 137:413–423

    Article  Google Scholar 

  • Butler R, Mulhern R (2005) Neurocognitive interventions for children and adolescents surviving cancer. J Pediatr Psychol 30:65–78

    Article  Google Scholar 

  • Collier TJ, Quirk GJ, Routtenberg A (1987) Separable roles of hippocampal granule cells in forgetting and pyramidal cells in remembering spatial information. Brain Res 409:316–328

    Article  Google Scholar 

  • Farrer LA, Cupples LA, Haines JL, Hyman B, Kukull WA, Mayeux R, Myers RH, Pericak-Vance MA, Risch N, van Duijn CM (1997) Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. J Am Med Assoc 278:1349–1356

    Article  Google Scholar 

  • Fyhn M, Molden S, Witter M, Moser E, Moser M-B (2004) Spatial representation in the enthorhinal cortex. Science 305:1258–1264

    Article  ADS  Google Scholar 

  • Harada A, Teng J, Takei Y, Oguchi K, Hirokawa N (2002) MAP-2 is required for dendrite elongation, PKA anchoring in dendrites, and proper PKA signal transduction. J Cell Biol 158:541–549

    Article  Google Scholar 

  • Knouff C, Hinsdale ME, Mezdour H, Altenburg MK, Watanabe M, Quarfordt SH, Sullivan J, Maeda N (1999) ApoE structure determines VLDL clearance and atherosclerosis in mice. J Clin Invest 103:1579–1586

    Article  Google Scholar 

  • Leutgeb S, Leutgeb J, Treves A, Moser M-B, Moser E (2004) Distinct ensemble codes in hippoacampal areas CA3 and CA1. Science 305:1295–1298

    Article  ADS  Google Scholar 

  • Madsen TM, Kristjansen PEG, Bolwig TG, Wortwein G (2003) Arrested neuronal proliferation and impaired hippocampal function following fractionated brain irradiation in the adult rat. Neuroscience 119:635–642

    Article  Google Scholar 

  • Mahley RW (1988) Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. Science 240:622–630

    Article  ADS  Google Scholar 

  • Mickley GA, Ferguson JL, Mulvihill MA, Nemeth TJ (1989) Progressive behavioral changes during the maturation of rats with early radiation-induced hypoplasia of fascia dentata granule cells. Neurotoxicol Teratol 11:385–393

    Article  Google Scholar 

  • Mizumatsu S, Monje M, Morhardt D, Rola R, Palmer TD, Fike JR (2003) Extreme sensitivity of adult neurogenesis to low doses of X-irradiation. Cancer Res 63:4021–4027

    Google Scholar 

  • Monje ML, Mizumatsu S, Fike JR, Palmer TD (2002) Irradiation induces neural precursor-cell dysfunction. Nat Med 8:955–962

    Article  Google Scholar 

  • Moreira RCM, Moreira MV, Bueno JLO, Xavier GF (1997) Hippocampal lesions induced by ionizing radiation: a parametric study. J Neurosci Meth 75:41–47

    Article  Google Scholar 

  • Morris R, Garrud P, Rawlins J, O’Keefe J (1982) Place navigation impaired in rats with hippocampal lesions. Nature 297:681–683

    Article  ADS  Google Scholar 

  • Paxinos G, Franklin K (2001) The mouse brain in stereotaxic coordinates. Academic Press San Diego, CA

    Google Scholar 

  • Raber J (2004) Differential gene actions of polymorphic alleles at the APOE locus; potential role of androgens and androgen receptor-mediated signaling. Science of Aging (SAGE) Knowledge Environment (KE) posted March 17, 2004

  • Raber J, Fan Y, Matsumori Y, Weistein PR, Fike JR, Liu J (2004a) Irradiation attenuates neurogenesis in the dentate gyrus and exacerbates ischemia-induced functional deficits. Ann Neurol 55:381–390

    Article  Google Scholar 

  • Raber J, Rola R, LeFevour A, Morhardt D, Curley J, Mizumatsu S, VandenBerg S, Fike JR (2004b) Radiation-induced cognitive impairments are associated with changes in indicators of hippocampal neurogenesis. Radiat Res 162:39–47

    Article  Google Scholar 

  • Rola R, Sarkissian V, Obenaus A, Nelson GA, Otsuka S, Limoli CL, Fike JR (2004) High LET irradiation induced inflammation and persistent changes in markers of hippocampal neurogenesis. Radiat Res 164:556–560

    Article  Google Scholar 

  • Roman DD, Sperduto PW (1995) Neuropsychological effects of cranial radiation: current knowledge and future directions. Int J Radiat Oncol Biol Phys 31:983–998

    Google Scholar 

  • Stubley-Weatherly L, Harding J, Wright J (1996) Effects of discrete kaininc acid-induced hippocampal lesions on spatial and contextual learning and memory in rats. Brain Res 716:29–38

    Article  Google Scholar 

  • Sullivan PM, Mezdour H, Aratani Y, Knouff C, Najib J, Reddick RL, Quarfordt SH, Maeda N (1997) Targeted replacement of the mouse apolipoprotein E gene with the common human APOE3 allele enhances diet-induced hypercholesterolemia and atherosclerosis. J Biol Chem 272:17972–17980

    Article  Google Scholar 

  • Sullivan PM, Mezdour H, Quarfordt SH, Maeda N (1998) Type III hyperlipoproteinemia and spontaneous atherosclerosis in mice resulting from gene replacement of mouse Apoe with human Apoe*2. J Clin Invest 102:130–135

    Article  Google Scholar 

  • Tada E, Parent JM, Lowenstein DH, Fike JR (2000) X-irradiation causes a prolonged reduction in cell proliferation in the dentate gyrus of adult rats. Neuroscience 99:33–41

    Article  Google Scholar 

  • Villasana L, Acevedo S, Poage C, Raber J (2006) Sex- and ApoE Isoform-dependent effects of radiation on cognitive function. Rad Res 166:883–891

    Article  Google Scholar 

  • Wallace RB, Graziadei R, Werboff J (1981) Behavioral correlates of focal hippocampal irradiation in rats II. Behavior related to adaptive function in a natural setting. Exp Brain Res 43:207–212

    Article  Google Scholar 

Download references

Acknowledgments

We thank Cara Poage for her help with the irradiation of the mice. This work was supported by IIRG-05-14021 (the Alzheimer’s Association) and NNJ05HE63G (NASA).

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Authors and Affiliations

  1. Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR, 97239, USA

    Laura Villasana, Timothy Pfankuch & Jacob Raber

  2. Department of Neurology and Division of Neuroscience ONPRC, Oregon Health and Science University, Portland, OR, 97239, USA

    Jacob Raber

Authors
  1. Laura Villasana
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  2. Timothy Pfankuch
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  3. Jacob Raber
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Correspondence to Jacob Raber.

Additional information

This manuscript is based on a contribution given at the “Heavy Ions in Therapy and Space Symposium 2009,” July 6–10, 2009, Cologne (Germany).

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Villasana, L., Pfankuch, T. & Raber, J. Isoform-dependent effects of apoE on doublecortin-positive cells and microtubule-associated protein 2 immunoreactivity following 137Cs irradiation. Radiat Environ Biophys 49, 421–426 (2010). https://doi.org/10.1007/s00411-010-0290-4

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  • DOI: https://doi.org/10.1007/s00411-010-0290-4

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