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Maternal seizures can affect the brain developing of offspring

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Abstract

To elucidate the impact of maternal seizures in the developing rat brain, pregnant Wistar rats were subjected to the pilocarpine-induced seizures and pups from different litters were studied at different ages. In the first 24 h of life, blood glucose and blood gases were analyzed. 14C-leucine [14C-Leu] incorporation was used to analyze protein synthesis at PN1, and Western Blot method was used to analyze protein levels of Bax, Bcl-2 and Poly(ADP-ribose) polymerase-1 (PARP-1) in the hippocampus (PN3-PN21). During the first 22 days of postnatal life, body weight gain, length, skull measures, tooth eruption, eye opening and righting reflex have been assessed. Pups from naive mothers were used as controls. Experimental pups showed a compensated metabolic acidosis and hyperglycemia. At PN1, the [14C-Leu] incorporation into different studied areas of experimental pups was lower than in the control pups. During development, the protein levels of Bax, Bcl-2 and PARP-1 in the hippocampus of experimental pups were altered when compared with control pups. A decreased level of pro- and anti-apoptotic proteins was verified in the early postnatal age (PN3), and an increased level of pro-apoptotic proteins concomitant with a reduced level of anti-apoptotic protein was observed at the later stages of the development (PN21). Experimental pups had a delay in postnatal growth and development beyond disturb in protein synthesis and some protein expression during development. These changes can be result from hormonal alterations linked to stress and/or hypoxic events caused by maternal epileptic seizures during pregnancy.

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References

  • Albrecht J, Smiatek M (1975) Effect of hypoxia, ischemia and carbon monoxide intoxication on in vivo protein synthesis in neuron and glia cell enriched fractions from rat brain. Acta Neuropath (Berl) 31:257–262

    Article  CAS  Google Scholar 

  • Amado D, Cavalheiro EA (1998) Hormonal and gestational parameters in female rats submitted to the pilocarpine model of epilepsy. Epilepsy Res 32:266–274

    Article  CAS  PubMed  Google Scholar 

  • Austin MP, Leader LR, Reilly N (2005) Prenatal stress, the hypothalamic-pituitary-adrenal axis, and fetal and infant neurobehavior. Early Hum Dev 81:917–926

    Article  CAS  PubMed  Google Scholar 

  • Autret A, Martin SJ (2009) Emerging role for members of the bcl-2 family in mitochondrial morphogenesis. Mol Cell 36:355–363

    Article  CAS  PubMed  Google Scholar 

  • Autret A, Martin SJ (2010) Bcl-2 family proteins and mitochondrial fission/fusion dynamics. Cell Mol Life Sci 67:1599–1606

    Article  CAS  PubMed  Google Scholar 

  • Cavalheiro EA, Silva DF, Turski WA, Calderazzo-Filho LS, Bortolotto ZA, Turski L (1987) The susceptibility of rats to pilocarpine-induced seizures is age-dependent. Dev Brain Res 37:43–58

    Article  CAS  Google Scholar 

  • Challis JRG, Matthews SG, Gibb W (2000) Endocrine and paracrine regulation of birth at term and preterm. Endocr Rev 21:514–555

    CAS  PubMed  Google Scholar 

  • CIOMS/OMS (1985) Council for International Organizations of Medical Services. WHO Distribution and sales service, 1211 Geneva 27, Switzerland, International Guiding Principles for Biomedical Research Involving Animals.

  • Clemens MJ, Bushell M, Jeffrey IW, Pain VM, Morley SJ (2000) Translation initiation factor modifications and the regulation of protein synthesis in apoptotic cells. Cell Death Differ 7(7):603–615

    Article  CAS  PubMed  Google Scholar 

  • Cosmi EV, Luzi G, Gori F, Chiodi A (1990) Response of utero-placental fetal blood flow to stress situation and drugs. Eur J Obstet Gynecol Reprod Biol 36:239–245

    Article  CAS  PubMed  Google Scholar 

  • Ha HC, Snyder SH (2000) Poly (ADP-ribose) polymerase-1 in the nervous system. Neurobiol Dis 7:225–239

    Article  CAS  PubMed  Google Scholar 

  • Hawkins AJS (1991) Protein turnover: a functional appraisal. Funct Ecol 5:222–233

    Article  Google Scholar 

  • Herceg Z, Wang ZQ (2001) Functions of poly (ADP-ribose) polymerase (PARP) in DNA repair, genomic integrity and cell death. Mutat Res 477:97–110

    Article  CAS  PubMed  Google Scholar 

  • Hossmann K-A, Widmann R, Wiessner C, Dux E, Djuricic B, Röhn G (1992) Protein synthesis after global cerebral ischemia and selective vulnerability. In J pharmacology of cerebral ischemia, edited by Krieglstein. H. Oberpichler-Schwenk, Wissenschaftliche Verlagsgesellschaft, Stuttgart, p. 289

    Google Scholar 

  • Hvas C, Henriksen T, Ostergaard J, Dam M (2000) Epilepsy and pregnancy: effect of antiepileptic drugs and lifestyle on birthweight. Br J Obstet Gynaecol 107:896–902

    Article  CAS  Google Scholar 

  • Korsmeyer SJ (1999) BCL-2 gene family and the regulation of programmed cell. Death Cancer Res 59:1693s–1700s

    CAS  PubMed  Google Scholar 

  • Krause GS, Whithe BC, Aust SD, Nayini NR, Kumar KL (1988) Brain cell death following ischemia and reperfusion: a proposed biochemical consequence. Crit Care Med 16:714–726

    Article  CAS  PubMed  Google Scholar 

  • Lagercrantz H, Bistoletti P (1977) Cathecolamine release in the newborn infant at birth. Pediatr Res 11:889–893

    Article  CAS  PubMed  Google Scholar 

  • Lautier D, Lagueux J, Thibodeau J, Menard L, Poirier GG (1993) Molecular and biochemical features of poly (ADP-ribose) metabolism. Mol Cell Biochem 122:171–193

    Article  CAS  PubMed  Google Scholar 

  • Lee HY, Naha N, Kim JH, Jo MJ, Min KS, Seong HH, et al. (2008) Age- and area-dependent distinct effects of ethanol on bax and bcl-2 expression in prenatal rat brain. J Microbiol Biotechnol 18(9):1590–1598

    CAS  PubMed  Google Scholar 

  • Lima DC, Vale TG, Arganãraz GA, Varella PP, Frussa-Filho R, Cavalheiro EA, et al. (2010) Behavioral evaluation of adult rats exposed in utero to maternal epileptic seizures. Epilepsy Behav 18:45–49

    Article  PubMed  Google Scholar 

  • Lima DC, Cossa AC, Perosa SR, Oliveira EM, Junior JAS, Fernandes MJS, et al. (2011) Neuroglobin is up regulated in cerebellum of pups exposed to maternal epileptic seizures. Int J Dev Neurosci 29(8):891–897

    Article  CAS  PubMed  Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193:265–275

    CAS  PubMed  Google Scholar 

  • Meador KJ, Baker GA, Finnell RH, Kalayjian LA, Liporace JD, Loring DW, et al. (2006) In utero antiepileptic drug exposure: fetal death and malformations. Neurology 67:407–412

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Merry DE, Korsmeyer SJ (1997) Bcl-2 gene family in the nervous system. Annu Rev Neurosci 20:245–267

    Article  CAS  PubMed  Google Scholar 

  • Minkoff H, Schaffer R, Delke I, Grunevaum A (1985) Diagnosis of intracranial hemorrhage in utero after a maternal seizure. Obstet Gynecol 65:22S–24S

    CAS  PubMed  Google Scholar 

  • Northington FJ, Ferriero DM, Graham EM, Traystman RJ, Martin LJ (2001) Early neurodegeneration after hypoxia–ischemia in neonatal rat is necrosis while delayed neuronal death is apoptosis. Neurobiol Dis 8:207–219

    Article  CAS  PubMed  Google Scholar 

  • Nowak JTS, Fried RL, Lust D, Passonneau JV (1985) Changes in brain energy metabolism and protein synthesis following transient bilateral ischemia in the gerbil. J Neurochem 44:487–494

    Article  CAS  PubMed  Google Scholar 

  • Oltvai ZN, Milliman CL, Korsmeyer SJ (1993) Bcl-2 heterodimerizes in vivo with a conserved homolog, bax, that accelerates programed cell death. Cell 74:609–619

    Article  CAS  PubMed  Google Scholar 

  • Pospisilik JA, Knauf C, Joza N, Benit P, Orthofer M, Cani PD, et al. (2007) Targeted deletion of AIF decreases mitochondrial oxidative phosphorylation and protects from obesity and diabetes. Cell 131:476–491

    Article  CAS  PubMed  Google Scholar 

  • Procianoy RS, Silveira RC (2001) Hypoxic-ischemic syndrome. J Pediatr 77:S63–S70

    Article  Google Scholar 

  • Racine R (1972) Modification of seizure activity by electrical stimulation II. Motor seizure. Electroencephalogr Clin Neurophysiol 32:281–294

    Article  CAS  PubMed  Google Scholar 

  • Ramachandra R, Subramanian T (2011) Atlas of the neonatal rat brain, 1st edn. CRC Press, Taylor & Francis Group, New York

    Book  Google Scholar 

  • Smulson ME, Simbulan-Rosenthal CM, Boulares AH, Yakovlev A, Stoica B, Iyer S, et al. (2000) Roles of poly(ADP-ribosyl)ation and PARP in apoptosis, DNA repair, genomic stability and functions of p53 and E2F-1. Adv Enzym Regul 40:183–215

    Article  CAS  Google Scholar 

  • Tuor UI, Manley JJ, Fyfe CA, Bascaramurty S (1999) Dexamethasone effects on cerebral protein synthesis prior to and following hypoxia-ischemia in immature rat. Brain Res Bull 48(1):61–64

    Article  CAS  PubMed  Google Scholar 

  • Vale, TG (2007) Efeito de crises epilépticas maternas sobre o desenvolvimento da prole. PhD Thesis. Universidade Federal de São Paulo, Departamento de Neurologia e Neurocirurgia, Unpublished results.

  • Vale TG, Silva AV, Lima DC, Lima E, Torres LB, Cossa AC, et al. (2010) Seizures during pregnancy modify the development of hippocampal interneurons of the offspring. Epilepsy Behav 19:20–25

    Article  PubMed  Google Scholar 

  • Valente SG, Naffah-Mazzacoratti MG, Pereira M, Silva I, Santos NF, Baracat EC, Cavalheiro EA, Amado D (2002) Castration in female rats modifies the development of pilocarpine model of epilepsy. Epilepsy Res 49:181–188

    Article  CAS  PubMed  Google Scholar 

  • Wang Y, Dawson VL, Dawson TM (2009) Poly ADP-ribose signals to mitochondrial AIF: a key event in parthanatos. Exp Neurol 218(2):193–202

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • White E (1996) Life, death and the pursuit of apoptosis. Genes Dev 10:1–15

    Article  CAS  PubMed  Google Scholar 

  • Yerby MS (2000) Quality of life, epilepsy advances, and the evolving role of anticonvulsants in women with epilepsy. Neurology 55:21–31

    Article  Google Scholar 

  • Yin XM, Oltvai ZN, Korsmeyer SJ (1994) BH1 and BH2 domains of bcl-2 are required for inhibition of apoptosis and heterodimerization with bax. Nature 369:321–323

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors are grateful for Hilda da Silva Reis for technical assistance, and Iara Ribeiro Silva for assistance with autorradiography. The study was supported by grants from FAPESP, CAPES, CNPq, PRONEX, CInAPCe, and FAPESP/CNPq/MCT-Instituto Nacional de Neurosciência Translacional.

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Correspondence to Ana Carolina Cossa.

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We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

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Cossa, A.C., Lima, D.C., do Vale, T.G. et al. Maternal seizures can affect the brain developing of offspring. Metab Brain Dis 31, 891–900 (2016). https://doi.org/10.1007/s11011-016-9825-y

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  • DOI: https://doi.org/10.1007/s11011-016-9825-y

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