Pre-gestational stress reduces the ratio of 5-HIAA to 5-HT and the expression of 5-HT1A receptor and serotonin transporter in the brain of foetal rat

BMC Neuroscience

Xuechuan Shi²  Yunbin Chen⁴  Hanhua Yang²  Hui Li¹  Hongwu Xu³  Yuejun Huang² 

[1]Mental Health Center of Shantou University, Tai Shan Rd, Shantou 515041, Guangdong, China

[2]Department of Pediatrics, Second Affiliated Hospital of Medical College of Shantou University, North Dongxia Rd, Shantou 515041, Guangdong, China

[3]Department of Neurosurgery, Second Affiliated Hospital of Medical College of Shantou University, North Dongxia Rd, Shantou 515041, Guangdong, China

[4]Maternal and Child Health Hospital of Guangdong Province, West Guangyuan Rd, GuangZhou 510010, Guangdong, China

关键词: Stress;    Serotonin transporter;    Serotonin;    HPA axis;    Corticosterone;   

Others  :  1170835
DOI  :  10.1186/1471-2202-13-22

 received in 2011-09-20, accepted in 2012-02-28,  发布年份 2012

【 摘 要 】

Background

Many studies have found that stress before or during pregnancy is linked to an increased incidence of behavioural disorders in offspring. However, few studies have investigated hypothalamic-pituitary-adrenal (HPA) axis activity and the serotonergic system as a consequence of pregestational stress. In the present study, we investigated the effect of pre-gestational stress on HPA axis activity in maternal rats and their foetuses and examined whether changes in HPA axis activity of maternal rats produced functional changes in the serotonergic system in the brain of foetuses.

Results

We used the behavioural tests to assess the model of chronic unpredictable stress (CUS) in maternal rats. We found the activity in the open field and sucrose consumption was lower for rats with CUS than for the controls. Body weight but not brain weight was higher for control foetuses than those from the CUS group. Serum corticosterone and corticotrophin-releasing hormone levels were significantly higher for mothers with CUS before pregnancy and their foetuses than for the controls. Levels of 5-hydroxytryptamine (5-HT) were higher in the hippocampus and hypothalamus of foetuses in the CUS group than in the controls, and 5-hydroxyindoleacetic acid (5-HIAA) levels were lower in the hippocampus in foetuses in the CUS group than in the control group. Levels of 5-HIAA in the hypothalamus did not differ between foetuses in the CUS group and in the control group. The ratio of 5-HIAA to 5-HT was significantly lower for foetuses in the CUS group than in the control group. Levels of 5-HT1A receptor were significantly lower in the foetal hippocampus in the CUS group than in the control group, with no significant difference in the hypothalamus. The levels of serotonin transporter (SERT) were lower in both the foetal hippocampus and foetal hypothalamus in the CUS group than in the control group.

Conclusions

Our data demonstrate that pre-gestational stress alters HPA axis activity in maternal rats and their foetuses, which is associated with functional changes in 5-HT activity (5-HT, 5-HIAA and ratio of 5-HIAA to 5-HT), as well as the levels of the 5-HT1A receptor and SERT in the hippocampus and hypothalamus of foetuses.

【 授权许可】

   
2012 Huang et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Kapoor A, Kostaki A, Janus C: The effects of prenatal stress on learning in adult offspring is dependent on the timing of the stressor. Behav Brain Res 2009, 197(1):144-149.
• [2]Li H, Zhang L, Fang Z, Lin L, Cairu Wu, Huang Q: Behavioral and neurobiological studies on the male progeny of maternal rats exposed to chronic unpredictable stress before pregnancy. Neurosci Lett 2010, 469(2):278-282.
• [3]Huang Y, Shi X, Hongwu Xu, Yang H, Chen T, Chen S, Chen X: Chronic unpredictable stress before pregnancy reduce the expression of brain-derived neurotrophic factor and N-methyl-D-aspartate receptor in hippocampus of offspring rats associated with impairment of memory. Neurochem Res 2010, 35(7):1038-1049.
• [4]Gao W, Paterson J, Abbott M, Carter S, Iusitini L: Maternal mental health and child behavior problems at 2 years: findings from the Pacific Islands Families Study. Aust N Z J Psychiatry 2007, 41:885-895.
• [5]Foster CJ, Garber J, Durlak JA: Current and past maternal depression, maternal interaction behaviors, and children's externalizing and internalizing symptoms. J Abnorm Child Psychol 2008, 36:527-537.
• [6]Spinelli S, Chefer S, Carson RE, Jagoda E, Lang L, Heilig M, Barr CS, Suomi SJ, Higley JD, Stein EA: Effects of early-life stress on serotonin(1A) receptors in juvenile Rhesus monkeys measured by positron emission tomography. Biol Psychiatry 2010, 67(12):1146-1153.
• [7]Brown MK, Luo Y: Bilobalide modulates serotonin-controlled behaviors in the nematode Caenorhabditis elegans. BMC Neurosci 2009, 10:62. BioMed Central Full Text
• [8]Davidson S, Prokonov D, Taler M, Maayan R, Harell D, Gil-Ad I, Weizman A: Effect of exposure to selective serotonin reuptake inhibitors in utero on fetal growth: potential role for the IGF-I and HPA axes. Pediatr Res 2009, 65(2):236-241.
• [9]Otten W, Kanitz E, Tuchscherer M, Brüssow KP, Nürnberg G: Repeated administrations of adrenocorticotropic hormone during late gestation in pigs: maternal cortisol response and effects on fetal HPA axis and brain neurotransmitter systems. Theriogenology 2008, 69(3):312-322.
• [10]Belay H, Burton CL, Lovic V, Meaney MJ, Sokolowski M, Fleming AS: Early adversity and serotonin transporter genotype interact with hippocampal glucocorticoid receptor mRNA expression, corticosterone, and behavior in adult male rats. Behav Neurosci 2011, 125(2):150-160.
• [11]Kim SJ, Kang JI, Namkoong K, Song DH: The effects of serotonin transporter promoter and monoamine oxidase A gene polymorphisms on trait emotional intelligence. Neuropsychobiology 2011, 64(4):224-230.
• [12]Pieper S, Out D, Bakermans-Kranenburg MJ, van Ijzendoorn MH: Behavioral and molecular genetics of dissociation: the role of the serotonin transporter gene promoter polymorphism (5-HTTLPR). J Trauma Stress 2011, 24(4):373-380.
• [13]Tjurmina OA, Armando I, Saavedra JM, Goldstein DS, Murphy DL: Exaggerated adrenomedullary response to immobilization in mice with targeted disruption of the serotonin transporter gene. Endocrinology 2002, 143:4520-4526.
• [14]Ansorge MS, Zhou M, Lira A, Hen R, Gingrich JA: Early-life blockade of the 5-HT transporter alters emotional behavior in adult mice. Science 2004, 306:879-881.
• [15]Li Q, Wichems C, Heils A, Van De Kar LD, Lesch KP, Murphy DL: Reduction of 5- hydroxytryptamine (5-HT)(1A)-mediated temperature and neuroendocrine responses and 5-HT(1A) binding sites in 5-HT transporter knockout mice. J Pharmacol Exp Ther 1999, 291:999-1007.
• [16]Hensler JG: Differential regulation of 5-HT1A receptor-G protein interactions in brain following chronic antidepressant administration. Neuropsychopharmacology 2002, 26:565-573.
• [17]Celada P, Puig M, Amargos-Bosch M, Adell A, Artigas F: The therapeutic role of 5-HT1A and 5-HT2A receptors in depression. J Psychiatry Neurosci 2004, 29:252-265.
• [18]Li Q, Holmes A, Ma L, Van de Kar LD, Garcia F, Murphy DL: Medial hypothalamic 5-hydroxytryptamine (5-HT)1A receptors regulate neuroendocrine responses to stress and exploratory locomotor activity: application of recombinant adenovirus containing 5-HT1A sequences. J Neurosci 2004, 24:10868-10877.
• [19]Kasper S, Tauscher J, Willeit M, Stamenkovic M, Neumeister A, Küfferle B, Barnas C, Stastny J, Praschak-Rieder N, Pezawas L, de Zwaan M, Quiner S, Pirker W, Asenbaum S, Podreka I, Brücke T: Receptor and transporter imaging studies in schizophrenia, depression, bulimia and Tourette's disorder-implications for psychopharmacology. World J Biol Psychiatry 2002, 3:133-133.
• [20]Sfikakis A, Galanopoulou P, Konstandi M, Tsakayannis D: Stress through handling for vaginal screening, serotonin, and ACTH response to ether. Pharmacol Biochem Behav 1996, 53:965-970.
• [21]Byers JP, Masters K, Sarver JG, Hassoun EA: Association between the levels of biogenic amines and superoxide anion production in brain regions of rats after subchronic exposure to TCDD. Toxicology 2006, 228(2-3):291-298.
• [22]Kilpatrick IC, Jones MW, Phillipson OT: A semiautomated analysis method for catecholamines, indoleamines, and some prominent metabolites in microdissected regions of the nervous system: an isocratic HPLC technique employing coulometric detection and minimal sample preparation. J Neurochem 1986, 46:1865-1876.
• [23]Commissiong JW: Monoamine metabolites: their relationship and lack of relationship to monoaminergic neuronal activity. Biochem Pharmacol 1985, 34:1127-1131.
• [24]Bilbo SD, Newsum NJ, Sprunger DB: Differential effects of neonatal handling on early life infection-induced alterations in cognition in adulthood. Brain Behav Immun 2007, 21:332-342.
• [25]Chomczynski P, Sacchi N: Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 1987, 162:156-159.
• [26]Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2T-ΔΔC method. Methods 2001, 25:402-408.
• [27]Herzog CJ, Czéh B, Corbach S, Wuttke W, Schulte-Herbrüggen O, Hellweg R, Flügge G, Fuchs E: Chronic social instability stress in female rats: a potential animal model for female depression. Neuroscience 2009, 159(3):982-992.
• [28]Aguilera G: HPA axis responsiveness to stress: Implications for healthy aging. Exp Gerontol 2011, 46(2-3):90-95.
• [29]de Weerth C, Buitelaar JK: Physiological stress reactivity in human pregnancy--a review. Neurosci Biobehav Rev 2005, 29(2):295-312.
• [30]Uchida T, Oki Y, Yanagawa Y, Fukuda A: A heterozygous deletion in the glutamate decarboxylase 67 gene enhances maternal and fetal stress vulnerability. Neurosci Res 2011, 69(4):276-282.
• [31]Entringer S, Kumsta R, Hellhammer DH, Wadhwa PD, Wüst S: Prenatal exposure to maternal psychosocial stress and HPA axis regulation in young adults. Horm Behav 2009, 55(2):292-298.
• [32]Charil A, Laplante DP, Vaillancourt C, King S: Prenatal stress and brain development. Brain Res Rev 2010, 65(1):56-79.
• [33]Van den Hove DL, Steinbusch HW, Scheepens A, Van de Berg WD, Kooiman LA, Boosten BJ, Prickaerts J, Blanco CE: Prenatal stress and neonatal rat brain development. Neuroscience 2006, 137(1):145-155.
• [34]Cintra A, Solfrini V, Bunnemann B, Okret S, Bortolotti F, Gustafsson JA, Fuxe K: Prenatal development of glucocorticoid receptor gene expression and immunoreactivity in the rat brain and pituitary gland: a combined in situ hybridization and immunocytochemical analysis. Neuroendocrinology 1993, 57:1133-1147.
• [35]Fujioka T, Sakata Y, Yamaguchi K, Shibasaki T, Kato H, Nakamura S: The effects of prenatal stress on the development of hypothalamic paraventricular neurons in fetal rats. Neuroscience 1999, 92:1079-1088.
• [36]Herman JP, Tasker JG, Ziegler DR, Cullinan WE: Local circuit regulation of paraventricular nucleus stress integration: glutamate-GABA connections. Pharmacol Biochem Behav 2002, 71:457-457.
• [37]Eliyahu D, Eitan G, Bernard L: Effects of chronic antidepressants and electroconvulsive shock on serotonergic neurotransmission in the rat hypothalamus. Prog Neuropsychopharmacol Biol Psychiatry 2002, 26:1029-1029.
• [38]Hoyer D, Hannon JP, Martin GR: Molecular, pharmacological and functional diversity of 5-HT receptors. Pharmacol Biochem Behav 2002, 71:533-554.
• [39]De Kloet ER, Vreugdenhil E, Oitzl MS, Joëls M: Brain corticosteroid receptor balance in health and disease. Endocr Rev 1998, 19:269-269.
• [40]Meijer OC, Kortekaas R, Oitzl MS, de Kloet ER: Acute rise in corticosterone facilitates 5-HT(1A) receptor-mediated behavioural responses. Eur J Pharmacol 1998, 351:7-14.
• [41]Leitch MM, Ingram CD, Young AH, McQuade R, Gartside SE: Flattening the corticosterone rhythm attenuates 5-HT1A auto- receptor function in the rat: relevance for depression. Neuropsychopharmacology 2003, 28:119-125.
• [42]Froger N, Palazzo E, Boni C, Hanoun N, Saurini F, Joubert C, Dutriez-Casteloot I, Enache M, Maccari S, Barden N, Cohen-Salmon C, Hamon M, Lanfumey L: Neurochemical and behavioral alterations in glucocorticoid receptor-impaired transgenic mice after chronic mild stress. J Neurosci 2004, 24:2787-2796.
• [43]Grippo AJ, Sullivan NR, Damjanoska KJ, Crane JW, Carrasco GA, Shi J, Chen Z, Garcia F, Muma NA, Van de Kar LD: Chronic mild stress induces behavioral and physiological changes, and may alter serotonin 1A receptor function, in male and cycling female rats. Psychopharmacology (Berl) 2005, 179:769-769.
• [44]Raap DK, DonCarlos L, Garcia F, Muma NA, Wolf WA, Battaglia G, Van de Kar LD: Estrogen desensitizes 5-HT(1A) receptors and reduces levels of G(z), G(i1) and G(i3) proteins in the hypothalamus. Neuropharmacology 2000, 39:1823-1832.
• [45]Zhou W, Cunningham KA, Thomas ML: Estrogen regulation of gene expression in the brain: a possible mechanism altering the response to psychostimulants in female rats. Brain Res Mol Brain Res 2002, 100:75-75.
• [46]Kia HK, Miquel MC, Brisorgueil MJ, Daval G, Riad M, El Mestikawy S, Hamon M, Vergé D: Immunocyotchemical localization of serotonin1A receptors in the rat central nervous system. J Comp Neurol 1996, 65:289-305.
• [47]Bier P, Ward NM: Is there a role for 5-HT1A agonists in the treatment of depression? Biol Psychiatry 2003, 53:193-203.
• [48]Dremencov E, Gur E, Lerer B, Newman ME: Effects of chronic antidepressants and electroconvulsive shock on serotonergic neurotransmission in the rat hippocampus. Prog Neuropsychopharmacol Biol Psychiatry 2003, 27(5):729-739.
• [49]Romberg C, Raffel J, Martin L, Sprengel R, Seeburg PH, Rawlins JN, Bannerman DM, Paulsen O: Induction and expression of GluA1 (GluR-A)-independent LTP in the hippocampus. Eur J Neurosci 2009, 29(6):1141-1152.
• [50]Dremencov E, Gur E, Lerer B, Newman ME: Effects of chronic antidepressants and electroconvulsive shock on serotonergic neurotransmission in the rat hypothalamus. Prog Neuropsychopharmacol Biol Psychiatry 2002, 26(6):1029-1034.
• [51]Takano H, Ito H, Takahashi H, Arakawa R, Okumura M, Kodaka F, Otsuka T, Kato M, Suhara T: Serotonergic neurotransmission in the living human brain: a positron emission tomography study using [¹¹C]dasb and [¹¹C]WAY100635 in young healthy men. Synapse 2011, 65(7):624-633.
• [52]Lidov HG, Molliver ME: An immunohistochemical study of serotonin neuron development in the rat: ascending pathways and terminal fields. Brain Res 1982, 8:389-430.
• [53]Andrews MH, Matthews SG: Programming of the hypothalamo-pituitary-adrenal axis: serotonergic involvement. Stress 2004, 7(1):15-27.
• [54]Barr CS, Newman TK, Shannon C, Parker C, Dvoskin RL, Becker ML, Schwandt M, Champoux M, Lesch KP, Goldman D, Suomi SJ, Higley JD: Rearing condition and rh5- HTTLPR interact to influence limbic-hypothalamic-pituitary-adrenal axis response to stress in infant macaques. Biol Psychiatry 2004, 55:733-738.
• [55]Bonnin A, Levitt P: Fetal, maternal, and placental sources of serotonin and new implications for developmental programming of the brain. Neuroscience 2011, 197:1-7.
• [56]Slotkin TA, Kreider ML, Tate CA, Seidler FJ: Critical prenatal and postnatal periods for persistent effects of dexamethasone on serotonergic and dopaminergic systems. Neuropsychopharmacology 2006, 31(5):904-911.
• [57]Slotkin TA, Seidler FJ: Mimicking maternal smoking and pharmacotherapy of preterm labor: interactions of fetal nicotine and dexamethasone on serotonin and dopamine synaptic function in adolescence and adulthood. Brain Res Bull 2010, 82(1-2):124-134.