Hostname: page-component-cd9895bd7-fscjk Total loading time: 0 Render date: 2024-12-26T14:31:39.020Z Has data issue: false hasContentIssue false
  • English
  • Français

Anxiety-like behavior and structural changes of the bed nucleus of the stria terminalis (BNST) in gestational protein-restricted male offspring

Published online by Cambridge University Press:  14 June 2018

D. B. Torres ,
A. Lopes ,
A. J. Rodrigues ,
J. J Cerqueira ,
N. Sousa ,
J. A. R. Gontijo  and
P. A. Boer
D. B. Torres
Affiliation:
Fetal Programming Laboratory and Hydroelectrolyte Metabolism Laboratory, Nucleus of Medicine and Experimental Surgery, Department of Internal Medicine, Faculty of Medical Sciences, State University of Campinas, Campinas, SP, Brazil
A. Lopes
Affiliation:
Fetal Programming Laboratory and Hydroelectrolyte Metabolism Laboratory, Nucleus of Medicine and Experimental Surgery, Department of Internal Medicine, Faculty of Medical Sciences, State University of Campinas, Campinas, SP, Brazil
A. J. Rodrigues
Affiliation:
Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga, Portugal
J. J Cerqueira
Affiliation:
Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga, Portugal
N. Sousa
Affiliation:
Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga, Portugal
J. A. R. Gontijo
Affiliation:
Fetal Programming Laboratory and Hydroelectrolyte Metabolism Laboratory, Nucleus of Medicine and Experimental Surgery, Department of Internal Medicine, Faculty of Medical Sciences, State University of Campinas, Campinas, SP, Brazil
P. A. Boer*
Affiliation:
Fetal Programming Laboratory and Hydroelectrolyte Metabolism Laboratory, Nucleus of Medicine and Experimental Surgery, Department of Internal Medicine, Faculty of Medical Sciences, State University of Campinas, Campinas, SP, Brazil
*
Address for correspondence: P. A. Boer, Department of Internal Medicine, School of Medicine, State University of Campinas, 126 Tessália Vieira de Camargo Street, 13083-887 Campinas, SP, Brazil. E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Animal evidence has suggested that maternal emotional and nutritional stress during pregnancy is associated with behavioral outcomes in offspring. The nature of the stresses applied may differ, but it is often assumed that the mother’s hippocampus–hypothalamic–pituitary–adrenal (HHPA) axis response releases higher levels of glucocorticoid hormones. The bed nucleus of the stria terminalis (BNST) is in a pivotal position to regulate the HHPA axis and the stress response, and it has been implicated in anxiety behavior. In the current study, to search whether BNST structural changes and neurochemical alterations are associated with anxiety-related behavior in adult gestational protein-restricted offspring relative to an age-matched normal protein diet (NP) rats, we conduct behavioral tests and, BNST dendritic tree analysis by Sholl analysis, associated to immunoblotting–protein quantification [11β-HSD2, GR, MR, AT1R, 5HT1A and 5HT2A, corticotrophin-releasing factor (CRH) and CRH1]. Dams were maintained either on isocaloric standard rodent chow [with NP content, 17% casein or low protein content (LP), 6% casein] chow throughout their entire pregnancy. Here, in rats subjected to gestational protein restriction, we found: (a) a significant reduction in dendritic length and impoverished dendritic arborization in BNST neurons; (b) an elevated plasmatic corticosterone levels; and (c) associated with enhanced anxiety-like behavior when compared with age-matched NP offspring. Moreover, altered protein (11β-HSD2, GR, MR and type 1 CRH receptors) expressions may underlie the increase in anxiety-like behavior in LP offspring. This work represents the first demonstration that BNST developmental plasticity by maternal protein restriction, resulting in fine structural changes and neurochemical alterations that are associated with modified behavioral states.

Keywords

anxiety-like behaviorBNSTdendritic remodelingfetal programminggestational protein restriction
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 9 , Issue 5 , October 2018 , pp. 536 - 543
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2018 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Lesage, J, Sebaai, N, Leonhardt, M, et al. Perinatal maternal undernutrition programs the offspring hypothalamo-pituitary-adrenal axis in mammals. Stress. 2006; 9, 183–198.Google Scholar
2. Ashton, N. Perinatal development and adult blood pressure. Braz J Med Biol Res. 2000; 33, 731–740.Google Scholar
3. O’Regan, D, Kenyon, JC, Seckl, JR, Holmes, MC. Glucocorticoid exposure in late gestation in the rat permanently programs gender-specific differences in adult cardiovascular and metabolic physiology. Am J Physiol. 2004; 287, 863–870.Google Scholar
4. Barker, DJP. In utero programming of chronic disease. Clin Sci (Lond). 1998; 95, 115–128.Google Scholar
5. Plagemann, A. ‘Fetal programming’ and ‘functional teratogenesis’: on epigenetic mechanisms and prevention of perinatally acquired lasting health risks. J Perinatal Med. 2004; 32, 297–305.Google Scholar
6. Seckl, JR. Prenatal glucocorticoids and long-term programming. Eur J Endocrinol. 2004; 151, 49–62.Google Scholar
7. Godfrey, K, Robinson, S, Barker, DJ, Osmond, C, Cox, V. Maternal nutrition in early and late pregnancy in relation to placental and fetal growth. Brit Med J. 1996; 312, 410–414.Google Scholar
8. Langley-Evans, SC, Phillips, GJ, Benediktsson, R, et al. Protein intake in pregnancy, placental glucocorticoid metabolism and the programming of hypertension in the rat. Placenta. 1996; 17, 169–172.Google Scholar
9. Mesquita, FF, Gontijo, JA, Boer, PA. Expression of renin-angiotensin system signalling compounds in maternal protein-restricted rats: effect on renal sodium excretion and blood pressure. Nephrol Dial Transplant. 2010a; 25, 380–388.Google Scholar
10. Mesquita, FF, Gontijo, JA, Boer, PA. Maternal undernutrition and the offspring kidney: from fetal to adult life. Braz J Med Biol Res. 2010b; 43, 1010–1018.Google Scholar
11. Rizzi, VH, Sene, LD, Fernandez, CD, Gontijo, JA, Boer, PA. Impact of long-term high-fat diet intake gestational protein-restricted offspring on kidney morphology and function. J Dev Orig Health Dis. 2017; 8, 89–100.Google Scholar
12. Woodall, SM, Johnston, BM, Breier, BH, Gluckman, PD. Chronic maternal undernutrition in the rat leads to delayed postnatal growth and elevated blood pressure of offspring. Pediatric Res. 1996; 40, 438–443.Google Scholar
13. Matsumoto, A. Synaptogenic action of sex steroids in developing and adult neuroendocrine brain. Psychoneuroendocrinology. 1991; 16, 25–40.Google Scholar
14. Welberg, LA, Seckl, JR. Prenatal stress, glucocorticoids and the programming of the brain. J Neuroendocrinol. 2001; 13, 113–128.Google Scholar
15. Langley-Evans, SC. Maternal carbenoxolone treatment lowers birthweight and induces hypertension in the offspring of rats fed a protein-replete diet. Clin Sci (Lond). 1997; 93, 423–429.Google Scholar
16. Stewart, PM, Whorwood, CB, Mason, JI. Type 2 11 beta-hydroxysteroid dehydrogenase in foetal and adult life. J Steroid Biochem Mol Biol. 1995; 55, 465–471.Google Scholar
17. Benediktsson, R, Lindsay, RS, Noble, J, Seckl, JR, Edwards, CR. Glucocorticoid exposure in utero: new model for adult hypertension. Lancet. 1993; 341, 339–341.Google Scholar
18. Darnaudéry, M, Maccari, S. Epigenetic programming of the stress response in male and female rats by prenatal restraint stress. Brain Res Rev. 2008; 57, 571–585.Google Scholar
19. Kapoor, A, Dunn, E, Kostaki, A, Andrews, MH, Matthews, SG. Fetal programming of hypothalamo-pituitary-adrenal function: prenatal stress and glucocorticoids. J Physiol. 2006; 572(Pt 1), 31–44.Google Scholar
20. Oliveira, M, Rodrigues, AJ, Leão, P, et al. The bed nucleus of stria terminalis and the amygdala as targets of antenatal glucocorticoids: implications for fear and anxiety responses. Psychopharmacology (Berl). 2012; 220, 443–453.Google Scholar
21. Duvarci, S, Bauer, EP, Paré, D. The bed nucleus of the stria terminalis mediates inter-individual variations in anxiety and fear. J Neurosci. 2009; 29, 10357–10361.Google Scholar
22. Pêgo, JM, Morgado, P, Pinto, LG, et al. Dissociation of the morphological correlates of stress-induced anxiety and fear. Eur J Neurosci. 2008; 27, 1503–1516.Google Scholar
23. Straube, T, Mentzel, HJ, Miltner, WH. Waiting for spiders: brain activation during anticipatory anxiety in spider phobics. Neuroimage. 2007; 37, 1427–1436.Google Scholar
24. Walker, DL, Toufexis, DJ, Davis, M. Role of the bed nucleus of the stria terminalis versus the amygdala in fear, stress, and anxiety. Eur J Pharmacol. 2003; 463, 199–216.Google Scholar
25. Walker, DL, Davis, M. Role of the extended amygdala in short-duration versus sustained fear: a tribute to Dr. Lennart Heimer. Brain Struct Funct. 2008; 213, 29–42.Google Scholar
26. Dunn, JD. Plasma corticosterone responses to electrical stimulation of the bed nucleus of the stria terminalis. Brain Res. 1987; 407, 327–331.Google Scholar
27. Herman, JP, Cullinan, WE, Watson, SJ. Involvement of the bed nucleus of the stria terminalis in tonic regulation of paraventricular hypothalamic CRH and AVP mRNA expression. J Neuroendocrinol. 1994; 6, 433–442.Google Scholar
28. Lopes, A, Torres, DB, Rodrigues, AJ, et al. Gestational protein restriction induces CA3 dendritic atrophy in dorsal hippocampal neurons but does not alter learning and memory performance in adult offspring. Int J Dev Neurosci. 2013; 31, 151–156.Google Scholar
29. Gibbs, R, Kolb, B. A method for vibratome sectioning of Golgi-Cox stained whole rat brain. J Neurosci Methods. 1998; 79, 1–4.Google Scholar
30. McDonald, AJ. Neurons of the bed nucleus of the stria terminalis: a golgi study in the rat. Brain Res Bull. 1983; 10, 111–120.Google Scholar
31. Almeida, SS, Tonkiss, J, Galler, JR. Prenatal protein malnutrition affects avoidance but not escape behavior in the elevated T-maze test. Physiol Behav. 1996; 60, 191–195.Google Scholar
32. Morgane, PJ, Mokler, DJ, Galler, JR. Effects of prenatal protein malnutrition on the hippocampal formation. Neurosci Biobehav Rev. 2002; 26, 471–483.Google Scholar
33. Morgane, PJ, Austin-LaFrance, R, Bronzino, J, et al. Prenatal malnutrition and development of the brain. Neurosci Biobehav Rev. 1993; 17, 91–128.Google Scholar
34. Strupp, BJ, Levitsky, DA. Enduring cognitive effects of early malnutrition: a theoretical reappraisal. J Nutrition. 1995; 125, 2221S–2232S.Google Scholar
35. Gillette, R, Reilly, MP, Topper, VY, et al. Anxiety-like behaviors in adulthood are altered in male but not female rats exposed to low dosages of polychlorinated biphenyls in utero. Hormone Behav. 2017; 87, 8–15.Google Scholar
36. Kwong, WY, Wild, AE, Roberts, P, Willis, AC, Fleming, TP. Maternal undernutrition during the preimplantation period of rat development causes blastocyst abnormalities and programming of postnatal hypertension. Development. 2000; 127, 4195–4202.Google Scholar
37. Ozaki, T, Nishina, H, Hanson, MA, Poston, L. Dietary restriction in pregnant rats causes gender-related hypertension and vascular dysfunction in offspring. J Physiol. 2001; 530(Pt 1), 141–152.Google Scholar
38. Davis, M, Walker, DL, Lee, Y. Amygdala and bed nucleus of the stria terminalis: differential roles in fear and anxiety measured with the acoustic startle reflex. Philos Trans R Soc B Biol Sci. 1997; 352, 1675–1687.Google Scholar
39. Pacak, K, Palkovits, M, Kopin, IJ, Goldstein, DS. Stress-induced norepinephrine release in the hypothalamic paraventricular nucleus and pituitary-adrenocortical and sympathoadrenal activity: in vivo microdialysis studies. Front Neuroendocrinol. 1995; 16, 89–150.Google Scholar
40. Allen, GV, Cechetto, DF. Functional and anatomical organization of cardiovascular pressor and depressor sites in the lateral hypothalamic area. II. Ascending projections. J Comp Neurol. 1993; 330, 421–438.Google Scholar
41. Stoddard, SL, Bergdall, VK, Townsend, DW, Levin, BE. Plasma catecholamines associated with hypothalamically-elicited flight behavior. Physiol Behav. 1986; 37, 709–715.Google Scholar
42. Fameli, M, Kitraki, E, Stylianopoulou, F. Effects of hyperactivity of the maternal hypothalamic-pituitary-adrenal (HPA) axis during pregnancy on the development of the HPA axis and brain monoamines of the offspring. Int J Dev Neurosci. 1994; 12, 651–659.Google Scholar
43. Hammack, SE, Roman, CW, Lezak, KR, et al. Roles for pituitary adenylate cyclase-activating peptide (PACAP) expression and signaling in the bed nucleus of the stria terminalis (BNST) in mediating the behavioral consequences of chronic stress. J Mol Neurosci. 2010; 42, 327–340.Google Scholar
44. Issa, AM, Rowe, W, Gauthier, S, Meaney, MJ. Hypothalamic–pituitary–adrenal activity in aged, cognitively impaired and cognitively unimpaired rats. J Neurosci. 1990; 10, 3247–3254.Google Scholar
45. Landfield, PW, Waymire, J, Lynch, G. Hippocampal aging and adrenocorticoids: a quantitative correlation. Science. 1978; 202, 1098–1102.Google Scholar
46. Meaney, MJ, Bodnoff, SR, O’Donnell, D, et al. Adrenal glucocorticoids as modulators of hippocampal neuron survival, repair, and function in the aged rat. In: Restorative Neurology (ed. Cuello C), 1993; pp. 267–289. Elsevier: New York.Google Scholar
47. Sapolsky, RM. A mechanism for glucocorticoid toxicity in the hippocampus: increased neuronal vulnerability to metabolic insults. J Neurosci. 1985; 5, 1228–1232.Google Scholar
48. Landfield, PW, Baskin, RK, Pitler, TA. Brain aging correlates: retardation by hormonal–pharmacological treatments. Science. 1981; 214, 581–584.Google Scholar
49. Vyas, A, Mitra, R, Shankaranarayana Rao, BS, Chattarji, S. Chronic stress induces contrasting patterns of dendritic remodeling in hippocampal and amygdaloid neurons. J Neurosci. 2002; 22, 6810–6818.Google Scholar
50. Vyas, A, Bernal, S, Chattarji, S. Effects of chronic stress on dendritic arborization in the central and extended amygdala. Brain Res. 2003; 965, 290–294.Google Scholar
51. Shepard, JD, Chambers, CO, Busch, C, Mount, A, Schulkin, J. Chronically elevated corticosterone in the dorsolateral bed nuclei of stria terminalis increases anxiety-like behavior. Behav Brain Res. 2009; 203, 146–149.Google Scholar
52. Chen, Y, Dubé, CM, Rice, CJ, Baram, TZ. Rapid loss of dendritic spines after stress involves derangement of spine dynamics by corticotropin-releasing hormone. J Neurosci. 2008; 28, 2903–2911.Google Scholar
53. Diaz, R, Brown, RW, Seckl, JR. Distinct ontogeny of glucocorticoid and mineralocorticoid receptor and 11beta-hydroxysteroid dehydrogenase types I and II mRNAs in the fetal rat brain suggest a complex control of glucocorticoid actions. J Neurosci. 1998; 18, 2570–2580.Google Scholar
54. Brown, RW, Diaz, R, Robson, AC, et al. The ontogeny of 11 beta-hydroxysteroid dehydrogenase type 2 and mineralocorticoid receptor gene expression reveal intricate control of glucocorticoid action in development. Endocrinol. 1996; 137, 794–797.Google Scholar
55. Brown, RW, Kotolevtsev, Y, Leckie, C, et al. Isolation and cloning of human placental 11β-hydroxysteroid dehydrogenase-2 cDNA. Biochem J. 1996; 313, 1007–1017.Google Scholar
56. Rowland, NE, Fregly, MJ. Induction of an appetite for sodium in rats that show no spontaneous preference for sodium chloride solution – the Fischer 344 strain. Behav Neurosci. 1988; 102, 961–968.Google Scholar