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Global Histone H4 Acetylation in the Olfactory Bulb of Lactating Rats with Different Patterns of Maternal Behavior

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Abstract

In rats, variations in the levels of neuromodulatory molecules and in the expression of their receptors are observed during pregnancy and postpartum. These changes may contribute to the development and management of maternal behavior. The frequency of licking the pups is used to evaluate maternal care, having mothers with low licking (LL) and high licking (HL) frequencies. Previously, we found that HL had increased levels of transcriptional expression of the receptors for serotonin (HTR1a, HTR1b), estrogen (Erα), dopamine (D1a), and prolactin (Prlr) than LL in the olfactory bulb (OB); however, the molecular mechanisms behind this phenomenon are unknown. Since evidences pointed out that epigenetic marks, which may alter gene expression, are modulated by environmental factors such as exercise, diet, maternal care, and xenobiotic exposure, our objective was to verify the acetylation levels of histone-H4 in the OB of LL and HL rats. Maternal behavior was studied for the first 7 postpartum days. LL (n = 4) and HL (n = 5) mothers were selected according to the behavior of licking their pups. Acetylation levels of histone-H4 were determined using the Global Histone-H4 Acetylation Assay Kit and expressed as ng/mg protein (mean ± SD). Analysis revealed that HL (278.36 ± 68.95) had increased H4 acetylation levels than LL (183.24 ± 73.05; p = 0.045). The enhanced expression of the previously studied receptors in the OB could be related, at least in part, to the hyperacetylation status of histone-H4 here observed. Afterward, the modulation of histone acetylation levels could exert a pivotal role through molecular mechanisms involved in the different patterns of maternal behavior.

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References

  • Beery AK, McEwen LM, MacIsaac JL, Francis DD, Kobor MS (2015) Natural variation in maternal care and cross-tissue patterns of oxytocin receptor gene methylation in rats. Horm Behav. doi:10.1016/j.yhbeh.2015.05.022

    PubMed  Google Scholar 

  • Bie B, Wang Y, Cai YQ, Zhang Z, Hou YY, Pan ZZ (2012) Upregulation of nerve growth factor in central amygdala increases sensitivity to opioid reward. Neuropsychopharmacol 37(13):2780–2788

    Article  CAS  Google Scholar 

  • Blaze J, Roth TL (2013) Exposure to caregiver maltreatment alters expression levels of epigenetic regulators in the medial prefrontal cortex. Int J Dev Neurosci 31(8):804–810. doi:10.1016/j.ijdevneu.2013.10.001

    Article  CAS  PubMed  Google Scholar 

  • Bradford MM (1976) A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:218–254

    Article  Google Scholar 

  • Bredy TW, Wu H, Crego C et al (2007) Histone modifications around individual BDNF gene promoters in prefrontal cortex are associated with extinction of conditioned fear. Learn Mem 14(4):268–276

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Caldji C, Tannenbaum B, Sharma S, Francis DD, Plotsky PM, Meaney MJ (1998) Maternal care during infancy regulates the development of neural systems mediating the expression of fearfulness in the rat. Proc Natl Acad Sci USA 95:5335–5340

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Champagne FA (2008) Epigenetic mechanisms and the transgenerational effects of maternal care. Front Neuroendocrinol 29:386–397

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Champagne FA, Curley JP (2008) Maternal regulation of estrogen receptor a methylation. Curr Opin Pharmacol 8:735–739

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Champagne F, Diorio J, Sharma S, Meaney MJ (2001) Naturally occurring variations in maternal behavior in the rat are associated with differences in estrogen-inducible central oxytocin receptors. Proc Natl Acad Sci USA 98:12736–12741

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Champagne FA, Francis DD, Mar A, Meaney MJ (2003) Variations in maternal care in the rat as a mediating influence for the effects of environment on development. Physiol Behav 79:359–371

    Article  CAS  PubMed  Google Scholar 

  • Champagne FA, Weaver IC, Diorio J, Dymov S, Szyf M, Meaney MJ (2006) Maternal care associated with methylation of the estrogen receptor-alpha1b promoter and estrogen receptor-alpha expression in the medial preoptic area of female offspring. Endocrinology 147(6):2909–2915

    Article  CAS  PubMed  Google Scholar 

  • Champagne DL, Bagot RC, Van Hasselt F, Ramakers G, Meaney MJ, Kloet ER (2008) Maternal care and hippocampal plasticity: evidence for experience- dependent structural plasticity, altered synaptic functioning, and differential responsiveness to glucocorticoids and stress. J Neurosci 28:6037–6045

    Article  CAS  PubMed  Google Scholar 

  • Chiu K, Lau WM, Lau HT, So KF, Chang RCC (2007) Micro-dissection of rat brain for RNA or protein extraction from specific brain region. J Vis Exp 7:269

    PubMed  Google Scholar 

  • De Moura AC, Lazzari VM, Becker RO, Gil MS, Ruthschilling CA, Agnes G, Almeida S, Da Veiga ABG, Lucion AB, Giovenardi M (2015) Gene expression in the CNS of lactating rats with different patterns of maternal behavior. Neurosci Res 99:8–15

    Article  PubMed  Google Scholar 

  • Elsner VR, Lovatel GA, Bertoldi K et al (2011) Effect of different exercise protocols on histone acetyltransferases and histone deacetylases activities in rat hippocampus. Neuroscience 192:580–587

    Article  CAS  PubMed  Google Scholar 

  • Francis DD, Diorio J, Liu D, Meaney MJ (1999) Nongenomic transmission across generations in maternal behavior and stress responses in the rat. Science 286:1155–1158

    Article  CAS  PubMed  Google Scholar 

  • Kouzarides T (2007) Chromatin modifications and their function. Cell 4:693–705

    Article  Google Scholar 

  • Kumar A, Choi KH, Renthal W, Tsankova NM, Theobald DE, Truong HT, Russo SJ, Laplant Q, Sasaki TS, Whistler KN et al (2005) Chromatin remodeling is a key mechanism underlying cocaine-induced plasticity in striatum. Neuron 48:303–314

    Article  CAS  PubMed  Google Scholar 

  • Lalonde ME, Cheng X, Cote J (2014) Histone target selection within chromatin: an exemplary case of teamwork. Genes Dev 28(10):1029–1041

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lenz KM, Sengelaub DR (2009) Maternal care effects on SNB motoneuron development: the mediating role of sensory afferent distribution and activity. Dev Neurobiol 69:603–615

    Article  PubMed  PubMed Central  Google Scholar 

  • Levenson JM, O’Riordan KJ, Brown KD, Trinh MA, Molfese DL, Sweatt JD (2004) Regulation of histone acetylation during memory formation in the hippocampus. J Biol Chem 279:40545–40559

    Article  CAS  PubMed  Google Scholar 

  • Lévy F, Keller M, Poindron P (2004) Olfactory regulation of maternal behavior in mammals. Horm Behav 46:284–302

    Article  PubMed  Google Scholar 

  • Liu D, Tannenbaum B, Caldji C, Francis DD, Freedman A, Sharma S (1997) Maternal care, hippocampal glucocorticoid receptor gene expression and hypothalamic–pituitary–adrenal responses to stress. Science 277:1659–1662

    Article  CAS  PubMed  Google Scholar 

  • Maccari S, Krugers HJ, Morley-Fletcher S, Szyf M, Brunton PJ (2014) The consequences of early-life adversity: neurobiological, behavioural and epigenetic adaptations. J Neuroendocrinol 26:707–723

    Article  CAS  PubMed  Google Scholar 

  • McGowan PO, Suderman M, Sasaki A, Huang TC, Hallett M, Meaney MJ, Szyf M (2011) Broad epigenetic signature of maternal care in the brain of adult rats. PLoS One 6(2):e14739. doi:10.1371/journal.pone.0014739

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mileva-Seitz VR, Bakermans-Kranenburg MJ, van IJzendoorn MH (2015) Genetic mechanisms of parenting. Horm Behav. doi:10.1016/j.yhbeh.2015.06.003

    PubMed  Google Scholar 

  • Myers MM, Brunelli SA, Squire JM, Shindeldecker RD, Hofer MA (1989) Maternal behavior of SHR rats and its relationship to offspring blood pressures. Dev Psychobiol 22:29–53

    Article  CAS  PubMed  Google Scholar 

  • Parent CI, Meaney MJ (2008) The influence of natural variations of maternal care on play fighting in the rat. Dev Psychobiol 50:767–776

    Article  PubMed  Google Scholar 

  • Patisaul HB, Scordalakes EM, Young LJ, Rissman EF (2003) Oxytocin, but not oxytocin receptor, is regulated by oestrogen receptor beta in the female mouse hypothalamus. J Neuroendocrinol 15(8):787–793

    Article  CAS  PubMed  Google Scholar 

  • Peña CJ, Neugut YD, Calarco CA, Champagne FA (2014) Effects of maternal care on the development of midbrain dopamine pathways and reward-directed behavior in female offspring. Eur J Neurosci 39:946–956

    Article  PubMed  Google Scholar 

  • Ruthschilling CA, Albiero G, Lazzari VM, Becker RO, de Moura AC, Lucion AB (2012) Analysis of transcriptional levels of the oxytocin receptor in different areas of the central nervous system and behaviors in high and low licking rats. Behav Brain Res 228:176–184

    Article  CAS  PubMed  Google Scholar 

  • Sharma RP (2005) Schizophrenia, epigenetics and ligand-activated nuclear receptors: a framework for chromatin therapeutics. Schizophr Res 72:79–90

    Article  PubMed  Google Scholar 

  • Stolzenberg DS, Stevens JS, Rissman EF (2012) Experience-facilitated improvements in pup retrieval; evidence for an epigenetic effect. Horm Behav 62(2):128–135

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tsankova NM, Berton O, Renthal W, Kumar A, Neve RL, Nestler EJ (2006) Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action. Nat Neurosci 9:519–525

    Article  CAS  PubMed  Google Scholar 

  • Veenema AH, Neumann ID (2009) Maternal separation enhances offensive play-fighting, basal corticosterone and hypothalamic vasopressin mRNA expression in juvenile male rats. Psychoneuroendocrinology 34:463–467

    Article  CAS  PubMed  Google Scholar 

  • Warnault V, Darcq E, Levine A, Barak S, Ron D (2013) Chromatin remodeling—a novel strategy to control excessive alcohol drinking. Transl Psychiatry 3:e231. doi:10.1038/tp.2013.4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weaver IC (2007) Epigenetic programming by maternal behavior and pharmacological intervention. Nature versus nurture: let’s call the whole thing off. Epigenetics 2(1):22–28

    Article  PubMed  Google Scholar 

  • Weaver IC, Cervoni N, Champagne FA, D’Alessio AC, Sharma S, Seckl JR, Dymov S, Szyf M, Meaney MJ (2004) Epigenetic programming by maternal behavior. Nat Neurosci 7(8):847–854

    Article  CAS  PubMed  Google Scholar 

  • Weaver ICG, Meaney MJ, Szyf M (2006) Maternal care effects on the hippocampal transcriptome and anxiety-mediated behaviors in the offspring that are reversible in adulthood. Proc Natl Acad Sci USA 103(9):3480–3485. doi:10.1073/pnas.0507526103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yamawaki Y, Fuchikami M, Morinobu S, Segawa M, Matsumoto T, Yamawaki S (2012) Antidepressant-like effect of sodium butyrate (HDAC inhibitor) and its molecular mechanism of action in the rat hippocampus. World J Biol Psychiatry 13(6):458–467

    Article  PubMed  Google Scholar 

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Acknowledgments

We thank PROAP/UFCSPA, CAPES and FAPERGS for financial support.

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Correspondence to Ana Carolina de Moura.

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The authors have no financial conflicts of interest.

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All procedures performed in this study were in accordance with the ethical standards of CONCEA (Conselho Nacional de Controle de Experimentação Animal) and were approved by the Ethics Committee of UFCSPA (Protocol Number 788/09).

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de Moura, A.C., da Silva, I.R.V., Reinaldo, G. et al. Global Histone H4 Acetylation in the Olfactory Bulb of Lactating Rats with Different Patterns of Maternal Behavior. Cell Mol Neurobiol 36, 1209–1213 (2016). https://doi.org/10.1007/s10571-015-0306-3

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  • DOI: https://doi.org/10.1007/s10571-015-0306-3

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