Skip to main content

Advertisement

Log in

Neuronal Analysis and Behaviour in Prenatally Gamma-Irradiated Rats

  • Original Research
  • Published:
Cellular and Molecular Neurobiology Aims and scope Submit manuscript

Abstract

The intrauterinal development in mammals represents a very sensitive period of life in relation to many environmental factors, including ionizing radiation (IR). The developing nervous system is particularly vulnerable to IR, and the consequences of exposure are of importance because of its potential health risks. The aim of our work was to assess whether prenatal irradiation of rats on the 17th day of embryonic development with a dose of 1 Gy would affect the formation of new cells and the number of mature neurons in the hippocampus and the selected forms of behaviour in the postnatal period. Male progeny of irradiated and control females was tested at ages of 3 weeks, 2 and 3 months. The number of mitotically active cells in the gyrus dentatus (GD) of the hippocampus was significantly reduced in irradiated rats aged 3 weeks. In irradiated rats aged 2 months, a significant reduction of mature neurons in CA1 area and in GD of the hippocampus was observed. The IR negatively influenced the spatial memory in Morris water maze, significantly decreased the exploratory behaviour and increased the anxiety-like behaviour in elevated plus-maze in rats aged 2 months. No significant differences were observed in animals aged 3 months compared with controls of the same age. A significant correlation between the number of mature neurons in the hilus and of the cognitive performances was found. Our results show that a low dose of radiation applied during the sensitive phase of brain development can influence the level of neurogenesis in the subgranular zone of GD and cause an impairment of the postnatal development of mental functions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Abayomi OK (1996) Pathogenesis of irradiation-induced cognitive dysfunction. Acta Oncol 35:659–663

    Article  CAS  PubMed  Google Scholar 

  • Abrous DN, Koehl M, Le Moal M (2005) Adult neurogenesis: from precursors to network and physiology. Physiol Rev 85:523–569

    Article  CAS  PubMed  Google Scholar 

  • Altman J (1963) Autoradiographic investigation of cell proliferation in the brains of rats and cats. Anat Rec 145:573–591

    Article  CAS  PubMed  Google Scholar 

  • Baskar R, Devi PU (1996) Long-term effects of prenatal exposure to low level of gamma radiation in neurophysiology of mouse. Indian J Exp Biol 34:887–890

    CAS  PubMed  Google Scholar 

  • Baskar R, Devi PU (2000) Influence of gestational age to low level gamma irradiation on postnatal behavior in mice. Neurotoxicol Teratol 22:593–602

    Article  CAS  PubMed  Google Scholar 

  • Ben Abdallah NM-B, Slomianka L, Vyssotski AL, Lipp H-P (2008) Early age-related changes in adult hippocampal neurogenesis in C57 mice. Neurobiol Aging 31(1):151–161

    Article  PubMed  Google Scholar 

  • Brandeis R, Brandys Y, Yehuda S (1989) The Use of the Morris Water Maze in the Study of Memory and Learning. Int J Neurosci 48:29–69

    Article  CAS  PubMed  Google Scholar 

  • Brent RL, Gorson RO (1972) Radiation exposure in pregnancy. Curr Probl Radiol 2:1–48

    Google Scholar 

  • Bromet EJ, Havenaar JM, Guey LT (2011) A 25 year retrospective review of the psychological consequences of the Chernobyl accident. Am J Clin Oncol 23(4):297–305

    Article  CAS  Google Scholar 

  • Bruni JE, Persaud TVN, Huang W, Froese G (1993) Postnatal development of the rat CNS following in utero exposure to a low dose of ionizing radiation. Exp Toxicol Pathol 45(4):223–231

    Article  CAS  PubMed  Google Scholar 

  • Cameron HA, Woolley CS, McEwen BS, Gould E (1993) Differentiation of newly born neurons and glia in the dentate gyrus of the adult rat. Eur J Neurosci 56:337–344

    Article  CAS  Google Scholar 

  • Crossen JR, Garwood D, Glatstein E, Neuwelt EA (1994) Neurobehavioral sequel of cranial irradiation in adults: a review of radiation-induced encephalopathy. J Clin Oncol 12:627–642

    CAS  PubMed  Google Scholar 

  • D’Hooge R, De Deyn PP (2001) Applications of the Morris water maze in the study of learning and memory. Brain Res Rev 36:60–90

    Article  PubMed  Google Scholar 

  • Donnelly EH, Smith JM, Farfán EB, Ozcan I (2011) Prenatal radiation exposure: background material for counseling pregnant patients following exposure to radiation. Disaster Med Pub Health Preparedness 5(1):62–68

    Article  Google Scholar 

  • Eliott BM, Grunberg NE (2005) Effects of social and physical enrichment on open field activity differ in male and female Sprague-Dawley rats. Behav Brain Res 165:187–196

    Article  Google Scholar 

  • Eriksson PS, Perfilieva E, Björk-Eriksson T, Alborn A-M, Nordborg C, Peterson DA, Gage FH (1998) Neurogenesis in the adult human hippocampus. Nat Med 4:1313–1317

    Article  CAS  PubMed  Google Scholar 

  • Fan Y, Liu Z, Weinstein PR, Fike JR, Liu J (2007) Environmental enrichment enhances neurogenesis and improves functional outcome after cranial irradiation. Eur J Neurosci 25:38–46

    Article  PubMed  Google Scholar 

  • Gould E (2007) How widespread is adult neurogenesis in mammals? Nat Rev Neurosci 8:481–488

    Article  CAS  PubMed  Google Scholar 

  • Gould E, Cameron HA, Daniels DC, Woolley CS, McEwen BS (1992) Adrenal hormones suppress cell division in the adult rat dentate gyrus. J Neurosci 12:3642–3650

    CAS  PubMed  Google Scholar 

  • Gross CG (2000) Neurogenesis in the adult brain: death of a dogma. Nat Rev Neurosci 1:67–73

    Article  CAS  PubMed  Google Scholar 

  • Hamdorf G, Shahar A, Cervós-Navarro J, Scheffler A, Sparenberg A, Skoberla A (1990) Morphological changes in cultures of hippocampus following prenatal irradiation in the rat. J Neurosci Res 26(3):327–333

    Article  CAS  PubMed  Google Scholar 

  • Hellström NAK, Björk-Eriksson T, Blomgren K, Kuhn G (2009) Differential recovery of neural stem cells in the subventricular zone and dentate gyrus after ionizing radiation. Stem Cells 27:634–641

    Article  PubMed  Google Scholar 

  • Hossain M, Devi PU (2000) Effect of irradiation at the early fetal stage on adult brain function in the mouse: locomotor activity. Int J Radiat Biol 76(10):1397–1402

    Article  CAS  PubMed  Google Scholar 

  • Hossain M, Chetana M, Devi PU (2005) Late effect of prenatal irradiation on the hippocampal histology and brain weight in adult mice. Int J Dev Neurosci 23:307–313

    Article  CAS  PubMed  Google Scholar 

  • Isono M, Otsu M, Konishi T, Matsubarad K, Tanabea T, Nakayamae T, Inouea N (2012) Proliferation and differentiation of neural stem cells irradiated with X-rays in logarithmic growth phase. J Neurosci Res 73:263–268

    Article  CAS  Google Scholar 

  • Jensh RP, Brent RL, Vogel WH (1986) Studies concerning the effects of low level prenatal x-irradiation on postnatal growth and adult behaviour in the wistar rat. Int J Radiat Biol Relat Stud Phys Chem Med 50(6):1069–1081

    Article  CAS  PubMed  Google Scholar 

  • Jensh RP, Brent RL, Vogel WH (1987) Studies of the effect of 0,4 and 0,6 Gy prenatal X-irradiation on postnatal and adult behavior in the Wistar rat. Teratology 35:53–61

    Article  CAS  PubMed  Google Scholar 

  • Jensh RP, Eisenman LM, Brent RL (1995) Postnatal neurophysiologic effects of prenatal x-irradiation. Int J Radiat Biol 67(2):217–227

    Article  CAS  PubMed  Google Scholar 

  • Jin K, Minami M, Lan JQ, Mao XO, Batteur S, Simon RP, Greenberg DA (2001) Neurogenesis in dentate subgranular zone and rostral subventricular zone after focal cerebral ischemia in the rat. PNAS 98:4710–4715

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kempermann G (2002) Why new neurons? Possible functions for adult hippocampal neurogenesis. J Neurosci 22:635–638

    CAS  PubMed  Google Scholar 

  • Kitamura M, Itoh K, Matsumoto A, Hayashi Y, Sasaki R, Imai Y, Itoh H (2001) Prenatal ionizing radiation-induced apoptosis of the developing murine brain with special references to the expression of some proteins. Kobe J Med Sci 47:59–76

    CAS  PubMed  Google Scholar 

  • Kuhn HG, Winkler J, Kempermann G et al (1997) Epidermal growth factor and fibroblast growth factor-2 have different effects on neural progenitors in the adult rat brain. J Neurosci 17:5820–5829

    CAS  PubMed  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  CAS  PubMed  Google Scholar 

  • Miki T, Sawada K, Sun XZ, Hisano S, Takeuchi Y, Fukui Y (1999) Abnormal distribution of hippocampal mossy fibres in rats exposed to X-radiation in utero. Dev Brain Res 112:275–280

    Article  CAS  Google Scholar 

  • Minamisawa T, Hirokaga K (1996) Long-term changes on open-field activity of male mice irradiated with low levels of gamma rays at late stage of foetal development. J Radiat Res 37:117–124

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Monje M (2008) Cranial radiation therapy and damage to hippocampal neurogenesis. Dev Disabil Res Rev 14:238–242

    Article  PubMed  Google Scholar 

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

  • Monje ML, Palmer T (2003) Radiation injury and neurogenesis. Curr Opin Neurol 16:129–134

    Article  PubMed  Google Scholar 

  • Morris R (1984) Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods 11:47–60

    Article  CAS  PubMed  Google Scholar 

  • Nakatomi H, Kuriu T, Okabe S, Yamamoto SI, Hatano O, Kawahara N, Tamura A, Kirino T, Nakafuku M (2002) Regeneration of hippocampal pyramidal neurons after ischemic brain injury by recruitment of endogenous neural progenitors. Cell 110:429–441

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Ramirez-Amaya V, Marrone DF, Gage FH, Worley PF, Barnes CA (2006) Integration of new neurons into functional neural networks. J Neurosci 26:12237–12241

    Article  CAS  PubMed  Google Scholar 

  • Ramos A, Mormede P (1998) Stress and emotionality: a multidimensional and genetic approach. Neurosci Biobehav Rev 22(1):33–57

    Article  CAS  PubMed  Google Scholar 

  • Rice D, Barone S Jr (2000) Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models. Environ Health Persp 108:511–533

    Article  Google Scholar 

  • Rodier PM (1980) Chronology of neuron development: animal studies and their clinical implications. Dev Med Child Neurol 22:525–545

    Article  CAS  PubMed  Google Scholar 

  • Rola R, Raber J, Rizk A, Otsuka S, VandenBerg SR, Morhardt DR, Fike J (2004) Radiation-induced impairment of hippocampal neurogenesis is associated with cognitive deficits in young mice. Exp Neurol 188:316–330

    Article  CAS  PubMed  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

    Article  CAS  PubMed  Google Scholar 

  • Rosi S, Andres-Mach M, Fishman KM, Levy W, Ferguson RA, Fike JR (2008) Cranial irradiation alters the behaviorally induced immediate-early gene arc (activity-regulated cytoskeleton-associated protein). Cancer Res 68:9763–9770

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Russell LB, Russell WL (1954) An analysis of the changing radiation response of the developing mouse embryo. Cell Physiol 43:103–149

    Article  CAS  Google Scholar 

  • Saxe MD, Battaglia F, Wang JW, Malleret G, David DJ, Monckton JE, Garcia AD, Sofroniew MV, Kandel ER, Santarelli L, Hen R, Drew MR (2006) Ablation of hippocampal neurogenesis impairs contextual fear conditioning and synaptic plasticity in the dentate gyrus. Proc Natl Acad Sci 103:17501–17506

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Schull WJ, Otake M (1999) Cognitive function and prenatal exposure to ionizing radiation. Teratology 59:222–226

    Article  CAS  PubMed  Google Scholar 

  • Schull WJ, Norton S, Jensh RP (1990) Ionizing radiation and the developing brain. Neurotoxicol Teratol 12(3):249–260

    Article  CAS  PubMed  Google Scholar 

  • Shaw P, Duncan A, Vouyouka A, Ozsvath K (2011) Radiation exposure and pregnancy. J Vasc Surg 53(1):28S–34S

    Article  PubMed  Google Scholar 

  • Shi L, Adams MM, Long A, Carter CC, Bennett C, Sonntag WE, Nicolle MM, Robbins M, D’Agostino R, Brunso-Bechtold JK (2006) Spatial learning and memory deficits after whole-brain irradiation are associated with changes in NMDA receptor subunits in the hippocampus. Radiat Res 166:892–899

    Article  CAS  PubMed  Google Scholar 

  • Shors TJ, Miesegaes G, Beylin A, Zhao M, Rydel T, Gould E (2001) Neurogenesis in the adult is involved in the formation of trace memories. Nature 414:372–376

    Article  Google Scholar 

  • Shors TJ, Townsend DA, Zhao M, Kozorovitskiy Y, Gould E (2002) Neurogenesis may relate to some but not all types of hippocampal-dependent learning. Hippocampus 12:578–584

    Article  PubMed Central  PubMed  Google Scholar 

  • Sienkiewicz ZJ, Saunders RD, Butland BK (1992) Prenatal irradiation and spatial memory in mice: investigation of critical period. Int J Radiat Biol 62:211–219

    Article  CAS  PubMed  Google Scholar 

  • Sienkiewicz ZJ, Haylock RG, Saunders RD (1999) Differential learning impairments produced by prenatal exposure to ionizing radiation in mice. Int J Radiat Biol 75(1):121–127

    Article  CAS  PubMed  Google Scholar 

  • Snyder JS, Hong NS, McDonald RJ, Wojtowicz JM (2005) A role for adult neurogenesis in spatial long-term memory. Neuroscience 130:843–852

    Article  CAS  PubMed  Google Scholar 

  • Surma-aho O, Niemela M, Vilkki J, Kouri M, Brander A, Salonen O, Paetau A, Kallio M, Pyykkonen J, Jaaskelainen J (2001) Adverse long-term effects of brain radiotherapy in adult low-grade glioma patients. Neurology 56:1285–1290

    Article  CAS  PubMed  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  CAS  PubMed  Google Scholar 

  • Takai N, Sun X-Z, Ando K, Mishima K, Takahashi S (2004) Ectopic neurons in the hippocampus may be a cause of learning disability after prenatal exposure to X-rays in rats. J Radiat Res 45:563–569

    Article  PubMed  Google Scholar 

  • Tau GZ, Peterson BS (2010) Normal development of brain circuits. Neuropsychopharmacol 35(1):147–168

    Article  Google Scholar 

  • Taupin P (2006) Adult neurogenesis in mammals. Curr Opin Mol Ther 8(4):345–351

    CAS  PubMed  Google Scholar 

  • Thompson A, Boekhoorn K, Van Dam AM, Lucassen PJ (2008) Changes in adult neurogenesis in neurodegenerative diseases: cause or consequence? Genes Brain Behav 7(1):28–42

    Article  PubMed  Google Scholar 

  • Tomášová L, Šmajda B, Ševc J (2012) Effects of prenatal irradiation on behaviour and hippocampal neurogenesis in adult rats. Acta Physiol Hung 99(2):126–132

    Article  PubMed  Google Scholar 

  • Van Praag H, Christie BR, Sejnowski TJ, Gage FH (1999) Running enhances neurogenesis, learning, and long-term potentiation in mice. Proc Natl Acad Sci 96:13427–13431

    Article  PubMed Central  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • West MJ (1993) Regionally specific loss of neurons in the aging human hippocampus. Neurobiol Aging 14(4):287–293

    Article  CAS  PubMed  Google Scholar 

  • Williams PM, Fletcher S (2010) Health effects of prenatal radiation exposure. Am Fam Physician 82(5):488–493

    PubMed  Google Scholar 

  • Winocur G, Wojtowicz JM, Sekeres M, Snyder JS, Wang S (2006) Inhibition of neurogenesis interferes with hippocampus-dependent memory function. Hippocampus 16:296–304

    Article  PubMed  Google Scholar 

  • Yan B, Bi X, He J, Zhang Y, Thakur S, Xu H, Gendron A, Kong J, Li X-M (2007) Quetiapine attenuates spatial memory impairment and hippocampal neurodegeneration induced by bilateral common carotid artery occlusion in mice. Life Sci 81:353–361

    Article  CAS  PubMed  Google Scholar 

  • Zhang R, Sun X-Z, Cui Ch, Sakata-Haga H, Sawada K, Ye Ch, Fukui Y (2007) Spatial learning and expression of neural cells adhesion molecule L1 in rats X-irradiation prenatally. J Med Invest 54:322–330

    Article  PubMed  Google Scholar 

  • Zhao C, Teng EM, Summers RG Jr, Ming GL, Gage FH (2006) Distinct morphological stages of dentate granule neuron maturation in the adult mouse hippocampus. J Neurosci 26:3–11

    Article  CAS  PubMed  Google Scholar 

  • Zhao C, Deng W, Gage FH (2008) Mechanisms and functional implications af adult neurogenesis. Cell 132:645–660

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors gratefully acknowledge the excellent technical assistance of Ingrid Obšitošová and Eva Petrovičová. The project was supported by research Grant VEGA No. 1/0292/12 and Institutional Grant of P.J. Šafárik University in Košice VVGS PF No. 2012/27.

Conflict of interest

Natália Kokošová, Lenka Tomášová, Terézia Kisková and Beňadik Šmajda declares that they have no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Natália Kokošová.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kokošová, N., Tomášová, L., Kisková, T. et al. Neuronal Analysis and Behaviour in Prenatally Gamma-Irradiated Rats. Cell Mol Neurobiol 35, 45–55 (2015). https://doi.org/10.1007/s10571-014-0144-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10571-014-0144-8

Keywords

Navigation