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Early Life Stress and Post-Weaning High Fat Diet Alter Tyrosine Hydroxylase Regulation and AT1 Receptor Expression in the Adrenal Gland in a Sex Dependent Manner

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Abstract

Previous studies have shown that early life stress induced by maternal separation or non-handling can lead to behavioural deficits in rats and that these deficits can be alleviated by providing palatable cafeteria high-fat diet (HFD). In these studies we investigated the effects of maternal separation or non-handling and HFD on tyrosine hydroxylase (TH) protein and TH phosphorylation at Ser40 (pSer40TH) and the expression of angiotensin II receptor type 1 (AT1R) protein in the adrenal gland as markers of sympatho-adrenomedullary activation. After littering, Sprague–Dawley rats were assigned to short maternal separation, S15 (15 min), prolonged maternal separation, S180 (180 min) daily from postnatal days 2–14 or were non-handled (NH) until weaning. Siblings were exposed to HFD or chow from day 21 until 19 weeks when adrenals were harvested. Maternal separation and non-handling had no effects on adrenal TH protein in both sexes. We found an effect of HFD only in the females; HFD significantly increased TH levels in NH rats and pSer40TH in S180 rats (relative to corresponding chow-fed groups), but had no effect on AT1R expression in any group. In contrast, in male rats HFD had no effect on TH protein levels, but significantly increased pSer40TH across all treatment groups. There was no effect of HFD on AT1R expression in male rats; however, maternal separation (for 15 or 180 min) caused significant increases in AT1R expression (relative to NH group regardless of diet). This is the first study to report that early life stress and diet modulate TH protein, pSer40TH and AT1R protein levels in the adrenal gland in a sex dependent manner. These results are interpreted in respect to the potential adverse effects that these changes in the adrenal gland may have in males and females in adult life.

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Abbreviations

HPA:

Hypothalamic–pituitary–adrenal

HFD:

High fat diet

TH:

Tyrosine hydroxylase

AT1R:

Angiotensin II receptor type 1

Ser:

Serine residue

References

  1. Jackowski A, Perera TD, Abdallah CG, Garrido G, Tang CY, Martinez J, Mathew SJ, Gorman JM, Rosenblum LA, Smith EL, Dwork AJ, Shungu DC, Kaffman A, Gelernter J, Coplan JD, Kaufman J (2011) Early-life stress, corpus callosum development, hippocampal volumetrics, and anxious behavior in male nonhuman primates. Psychiatry Res 192:37–44

    Article  PubMed  Google Scholar 

  2. Ros-Simo C, Valverde O (2012) Early-life social experiences in mice affect emotional behaviour and hypothalamic-pituitary-adrenal axis function. Pharmacol Biochem Behav 102:434–441

    Article  PubMed  CAS  Google Scholar 

  3. McLaughlin KA, Kubzansky LD, Dunn EC, Waldinger R, Vaillant G, Koenen KC (2010) Childhood social environment, emotional reactivity to stress, and mood and anxiety disorders across the life course. Depress Anxiety 27:1087–1094

    Article  PubMed  Google Scholar 

  4. Faravelli C, Lo Sauro C, Lelli L, Pietrini F, Lazzeretti L, Godini L, Benni L, Fioravanti G, Talamba GA, Castellini G, Ricca V (2012) The role of life events and HPA axis in anxiety disorders: a review. Curr Pharm Des 18:5663–5674

    Article  PubMed  CAS  Google Scholar 

  5. Levine S (1959) The effects of differential infantile stimulation of emotionality at weaning. Canadian J Psychol 13:243–247

    Article  Google Scholar 

  6. Meaney MJ, Bhatnagar S, Diorio J, Larocque S, Francis D, O’Donnell D, Shanks N, Sharma S, Smythe J, Viau V (1993) Molecular basis for the development of individual differences in the hypothalamic-pituitary-adrenal stress response. Cell Mol Neurobiol 13:321–347

    Article  PubMed  CAS  Google Scholar 

  7. Huot RL, Thrivikraman KV, Meaney MJ, Plotsky PM (2001) Development of adult ethanol preference and anxiety as a consequence of neonatal maternal separation in long evans rats and reversal with antidepressant treatment. Psychopharmacology 158:366–373

    Article  PubMed  CAS  Google Scholar 

  8. Penke Z, Felszeghy K, Fernette B, Sage D, Nyakas C, Burlet A (2001) Postnatal maternal deprivation produces long-lasting modifications of the stress response, feeding and stress-related behaviour in the rat. Eur J Neurosci 14:747–755

    Article  PubMed  CAS  Google Scholar 

  9. Ladd CO, Thrivikraman KV, Huot RL, Plotsky PM (2005) Differential neuroendocrine responses to chronic variable stress in adult Long Evans rats exposed to handling-maternal separation as neonates. Psychoneuroendocrinology 30:520–533

    Article  PubMed  CAS  Google Scholar 

  10. Hofer MA (1973) Maternal separation affects infant rats’ behavior. Behav Biol 9:629–633

    Article  PubMed  CAS  Google Scholar 

  11. Maniam J, Morris MJ (2010) Palatable cafeteria diet ameliorates anxiety and depression-like symptoms following an adverse early environment. Psychoneuroendocrinology 35:717–728

    Article  PubMed  CAS  Google Scholar 

  12. Maniam J, Morris MJ (2010) Voluntary exercise and palatable high-fat diet both improve behavioural profile and stress responses in male rats exposed to early life stress: role of hippocampus. Psychoneuroendocrinology 35:1553–1564

    Article  PubMed  CAS  Google Scholar 

  13. McCarty R, Horbaly WG, Brown MS, Baucom K (1981) Effects of handling during infancy on the sympathetic-adrenal medullary system of rats. Dev Psychobiol 14:533–539

    Article  PubMed  CAS  Google Scholar 

  14. Diaz Lujan VE, Castellanos MM, Levin G, Suarez MM (2008) Amitriptyline: sex-dependent effect on sympathetic response and anxiety in rats submitted to early maternal separation and variable chronic stress in adulthood. Int J Dev Neurosci 26:415–422

    Article  PubMed  CAS  Google Scholar 

  15. Hennessy MB, Tamborski A, Schiml P, Lucot J (1989) The influence of maternal separation on plasma concentrations of ACTH, epinephrine, and norepinephrine in guinea pig pups. Physiol Behav 45:1147–1152

    Article  PubMed  CAS  Google Scholar 

  16. Faraday MM (2002) Rat sex and strain differences in responses to stress. Physiol Behav 75:507–522

    Article  PubMed  CAS  Google Scholar 

  17. Ma X, Chapleau MW, Whiteis CA, Abboud FM, Bielefeldt K (2001) Angiotensin selectively activates a subpopulation of postganglionic sympathetic neurons in mice. Circ Res 88:787–793

    Article  PubMed  CAS  Google Scholar 

  18. Powis DA, Obrien KJ (1991) Angiotensin-II increases catecholamine release from bovine adrenal-medulla but does not enhance that evoked by K+ depolarisation or by carbachol. J Neurochem 57:1461–1469

    Article  PubMed  CAS  Google Scholar 

  19. Baruchin A, Weisberg EP, Miner LL, Ennis D, Nisenbaum LK, Naylor E, Stricker EM, Zigmond MJ, Kaplan BB (1990) Effects of cold exposure on rat adrenal tyrosine hydroxylase: an analysis of RNA, protein, enzyme activity, and cofactor levels. J Neurochem 54:1769–1775

    Article  PubMed  CAS  Google Scholar 

  20. Fluharty SJ, Snyder GL, Stricker EM, Zigmond MJ (1983) Short-and long-term changes in adrenal tyrosine hydroxylase activity during insulin-induced hypoglycemia and cold stress. Brain Res 267:384–387

    Article  PubMed  CAS  Google Scholar 

  21. Kvetnansky R, Micutkova L, Rychkova N, Kubovcakova L, Mravec B, Filipenko M, Sabban EL, Krizanova O (2004) Quantitative evaluation of catecholamine enzymes gene expression in adrenal medulla and sympathetic Ganglia of stressed rats. Ann N Y Acad Sci 1018:356–369

    Article  PubMed  CAS  Google Scholar 

  22. Nankova B, Kvetnansky R, Hiremagalur B, Sabban B, Rusnak M, Sabban EL (1996) Immobilization stress elevates gene expression for catecholamine biosynthetic enzymes and some neuropeptides in rat sympathetic ganglia: effects of adrenocorticotropin and glucocorticoids. Endocrinology 137:5597–5604

    Article  PubMed  CAS  Google Scholar 

  23. Stromberg C, Tsutsumi K, Viswanathan M, Saavedra JM (1991) Angiotensin II AT1 receptors in rat superior cervical ganglia: characterization and stimulation of phosphoinositide hydrolysis. Eur J Pharmacol 208:331–336

    Article  PubMed  CAS  Google Scholar 

  24. Cierco M, Israel A (1994) Role of angiotensin AT(1) receptor in the cardiovascular-response to footshock. Eur J Pharmacol 251:103–106

    Article  PubMed  CAS  Google Scholar 

  25. Dendorfer A, Thornagel A, Raasch W, Grisk O, Tempel K, Dominiak P (2002) Angiotensin II induces catecholamine release by direct ganglionic excitation. Hypertension 40:348–354

    Article  PubMed  CAS  Google Scholar 

  26. Macht M (2008) How emotions affect eating: a five-way model. Appetite 50:1–11

    Article  PubMed  Google Scholar 

  27. Pecoraro N, Reyes F, Gomez F, Bhargava A, Dallman MF (2004) Chronic stress promotes palatable feeding, which reduces signs of stress: feedforward and feedback effects of chronic stress. Endocrinology 145:3754–3762

    Article  PubMed  CAS  Google Scholar 

  28. Kalil GZ, Haynes WG (2012) Sympathetic nervous system in obesity-related hypertension: mechanisms and clinical implications. Hypertens Res 35:4–16

    Article  PubMed  CAS  Google Scholar 

  29. Lambert EA, Straznicky NE, Lambert GW (2012) A sympathetic view of human obesity. Clin Auton Res (in press)

  30. Lee RM, Borkowski KR, Leenen FH, Tsoporis J, Coughlin M (1991) Interaction between sympathetic nervous system and adrenal medulla in the control of cardiovascular changes in hypertension. J Cardiovasc Pharmacol 17(Suppl 2):S114–S116

    Article  PubMed  Google Scholar 

  31. Grassi G, Quarti-Trevano F, Dell’oro R, Mancia G (2008) Essential hypertension and the sympathetic nervous system. Neurol Sci 29(Suppl 1):S33–S36

    Article  PubMed  Google Scholar 

  32. Grassi G, Seravalle G, Quarti-Trevano F (2010) The ‘neuroadrenergic hypothesis’ in hypertension: current evidence. Exp Physiol 95:581–586

    Article  PubMed  Google Scholar 

  33. Parati G, Esler M (2012) The human sympathetic nervous system: its relevance in hypertension and heart failure. Eur Heart J 33:1058–1066

    Article  PubMed  CAS  Google Scholar 

  34. Iwai M, Horiuchi M (2009) Devil and angel in the renin-angiotensin system: ACE-angiotensin II-AT1 receptor axis versus ACE2-angiotensin-(1–7)-Mas receptor axis. Hypertens Res 32:533–536

    Article  PubMed  CAS  Google Scholar 

  35. Bader M, Ganten D (2008) Update on tissue renin-angiotensin systems. J Mol Med 86:615–621

    Article  PubMed  CAS  Google Scholar 

  36. Mendelsohn ME, Karas RH (2005) Molecular and cellular basis of cardiovascular gender differences. Science 308:1583–1587

    Article  PubMed  CAS  Google Scholar 

  37. Bhupathy P, Haines CD, Leinwand LA (2010) Influence of sex hormones and phytoestrogens on heart disease in men and women. Womens Health (Lond Engl) 6:77–95

    Article  CAS  Google Scholar 

  38. Shiraev T, Chen H, Morris MJ (2009) Differential effects of restricted versus unlimited high-fat feeding in rats on fat mass, plasma hormones and brain appetite regulators. J Neuroendocrinol 21:602–609

    Article  PubMed  CAS  Google Scholar 

  39. Rajia S, Chen H, Morris MJ (2010) Maternal overnutrition impacts offspring adiposity and brain appetite markers-modulation by postweaning diet. J Neuroendocrinol 22:905–914

    PubMed  CAS  Google Scholar 

  40. Bobrovskaya L, Damanhuri HA, Ong LK, Schneider JJ, Dickson PW, Dunkley PR, Goodchild AK (2010) Signal transduction pathways and tyrosine hydroxylase regulation in the adrenal medulla following glucoprivation: an in vivo analysis. Neurochem Int 57:162–167

    Article  PubMed  CAS  Google Scholar 

  41. Gordon SL, Bobrovskaya L, Dunkley PR, Dickson PW (2009) Differential regulation of human tyrosine hydroxylase isoforms 1 and 2 in situ: isoform 2 is not phosphorylated at Ser35. Biochim Biophys Acta 1793:1860–1867

    Article  PubMed  CAS  Google Scholar 

  42. Dunkley PR, Bobrovskaya L, Graham ME, von Nagy-Felsobuki EI, Dickson PW (2004) Tyrosine hydroxylase phosphorylation: regulation and consequences. J Neurochem 91:1025–1043

    Article  PubMed  CAS  Google Scholar 

  43. Kumer SC, Vrana KE (1996) Intricate regulation of tyrosine hydroxylase activity and gene expression. J Neurochem 67:443–462

    Article  PubMed  CAS  Google Scholar 

  44. Bobrovskaya L, Gelain DP, Gilligan C, Dickson PW, Dunkley PR (2007) PACAP stimulates the sustained phosphorylation of tyrosine hydroxylase at serine 40. Cell Signal 19:1141–1149

    Article  PubMed  CAS  Google Scholar 

  45. Bobrovskaya L, Gilligan C, Bolster EK, Flaherty JJ, Dickson PW, Dunkley PR (2007) Sustained phosphorylation of tyrosine hydroxylase at serine 40: a novel mechanism for maintenance of catecholamine synthesis. J Neurochem 100:479–489

    Article  PubMed  CAS  Google Scholar 

  46. Kvetnansky R, Sabban EL, Palkovits M (2009) Catecholaminergic systems in stress: structural and molecular genetic approaches. Physiol Rev 89:535–606

    Article  PubMed  CAS  Google Scholar 

  47. Ong LK, Sominsky L, Dickson PW, Hodgson DM, Dunkley PR (2012) The in sustained phase of tyrosine hydroxylase activation vivo. Neurochem Res 37:1938–1943

    Article  PubMed  CAS  Google Scholar 

  48. Macova M, Armando I, Zhou J, Baiardi G, Tyurmin D, Larrayoz-Roldan IM, Saavedra JM (2008) Estrogen reduces aldosterone, upregulates adrenal angiotensin II AT2 receptors and normalizes adrenomedullary Fra-2 in ovariectomized rats. Neuroendocrinology 88:276–286

    Article  PubMed  CAS  Google Scholar 

  49. Bunn SJ, Marley PD (1989) Effects of angiotensin-II in cultured, bovine adrenal-medullary cells. Neuropeptides 13(2):121–132

    Article  PubMed  CAS  Google Scholar 

  50. Bobrovskaya L, Cheah TB, Bunn SJ, Dunkley PR (1998) Tyrosine hydroxylase in bovine adrenal chromaffin cells: angiotensin II-stimulated activity and phosphorylation of Ser19, Ser31, and Ser40. J Neurochem 70(6):2565–2573

    Article  PubMed  CAS  Google Scholar 

  51. Wu Z, Maric C, Roesch DM, Zheng W, Verbalis JG, Sandberg K (2003) Estrogen regulates adrenal angiotensin AT1 receptors by modulating AT1 receptor translation. Endocrinology 144:3251–3261

    Article  PubMed  CAS  Google Scholar 

  52. Roesch DM, Tian Y, Zheng W, Shi M, Verbalis JG, Sandberg K (2000) Estradiol attenuates angiotensin-induced aldosterone secretion in ovariectomized rats. Endocrinology 141:4629–4636

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by the Discovery Grant of the Australian Research Council, Hunter Medical Research Institute, University of Newcastle.

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The authors have nothing to disclose.

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Correspondence to Larisa Bobrovskaya.

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Larisa Bobrovskaya, Jayanthi Maniam contributed equally to this work.

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Bobrovskaya, L., Maniam, J., Ong, L.K. et al. Early Life Stress and Post-Weaning High Fat Diet Alter Tyrosine Hydroxylase Regulation and AT1 Receptor Expression in the Adrenal Gland in a Sex Dependent Manner. Neurochem Res 38, 826–833 (2013). https://doi.org/10.1007/s11064-013-0985-4

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  • DOI: https://doi.org/10.1007/s11064-013-0985-4

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