Skip to main content

Advertisement

SpringerLink
Log in

Neonatal Maternal Separation Alters Immune, Endocrine, and Behavioral Responses to Acute Theiler’s Virus Infection in Adult Mice

  • Original Research
  • Published:
Behavior Genetics Aims and scope Submit manuscript

Abstract

Previous studies have established a link between adverse early life events and subsequent disease vulnerability. The present study assessed the long-term effects of neonatal maternal separation on the response to Theiler’s murine encephalomyelitis virus infection, a model of multiple sclerosis. Balb/cJ mouse pups were separated from their dam for 180-min/day (180-min MS), 15-min/day (15-min MS), or left undisturbed from postnatal days 2–14. During adolescence, mice were infected with Theiler’s virus and sacrificed at days 14, 21, or 35 post-infection. Prolonged 180-min MS increased viral load and delayed viral clearance in the spinal cords of males and females, whereas brief 15-min MS increased the rate of viral clearance in females. The 15-min and 180-min MS mice exhibited blunted corticosterone responses during infection, suggesting that reduced HPA sensitivity may have altered the immune response to infection. These findings demonstrate that early life events alter vulnerability to CNS infection later in life. Therefore, this model could be used to study gene-environment interactions that contribute to individual differences in susceptibility to infectious and autoimmune diseases of the CNS.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  • Acheson ED (1977) Epidemiology of multiple sclerosis. Brit Med Bull 33:9–14

    PubMed  Google Scholar 

  • Ackerman SH, Keller SE, Schleifer SJ, Shindledecker RD, Camerino M, Hofer MA, Weiner H, Stein M (1988) Premature maternal separation and lymphocyte function. Brain Behav Immun 2:161–165

    PubMed  Google Scholar 

  • Ackerman KD, Heyman R, Rabin BS, Anderson BP, Houck PR, Frank E, Baum A (2002) Stressful life events precede exacerbations of multiple sclerosis. Psychosom Med 64:916–920

    PubMed  Google Scholar 

  • Alter M, Zhang ZX, Davanipour Z, Sobel E, Zibulewski J, Schwartz G, Friday G (1986) Multiple sclerosis and childhood infections. Neurology 36:1386–1389

    PubMed  Google Scholar 

  • Anda RF, Brown DW, Dube SR, Bremner JD, Felitti VJ, Giles WH (2008) Adverse childhood experiences and chronic obstructive pulmonary disease in adults. Am J Prev Med 34:396–403

    PubMed  Google Scholar 

  • Anisman H, Zaharia DM, Meaney MJ, Merali Z (1998) Do early-life events permanently alter behavioral and hormonal responses to stressors? Int J Dev Neurosci 16:149–164

    PubMed  Google Scholar 

  • Aubert C, Chamorro M, Brahic M (1987) Identification of Theiler’s infected cells in the central nervous system of the mouse during demyelinating disease. Microb Pathog 3:319–326

    PubMed  Google Scholar 

  • Avitsur R, Hunzekerb J, Sheridan JF (2006) Role of early stress in the individual differences in host response to viral infection. Brain Behav Immun 20:339–348

    PubMed  Google Scholar 

  • Bakker JM, Schmidt ED, Kroes H, Kavelaars A, Heijnen CJ, Tilders FJH, Van Rees EP (1997) Effects of neonatal dexamethasone treatment on the hypothalamic-pituitary adrenal axis and immune system of the rat. J Neuroimmunol 74:69–76

    PubMed  Google Scholar 

  • Bakker JM, Kavelaars A, Kamphuis PJGH, Cobelens PM, van Vugt HH, van Bel F, Heijnen CJ (2000) Neonatal dexamethasone treatment increases susceptibility to experimental autoimmue disease in adult rats. J Immunol 165:5932–5937

    PubMed  Google Scholar 

  • Bakker JM, Kavelaars A, Kamphuis PJGH, Zijlstra J, van Bel F, Heijnen CJ (2001) Neonatal dexamethasone treatment induces long-lasting changes in T-cell receptor Vβ repertoire in rats. J Neuroimmunol 112:47–54

    PubMed  Google Scholar 

  • Barker DJ (1997) Fetal nutrition and cardiovascular disease in later life. Br Med Bull 53:96–108

    PubMed  Google Scholar 

  • Barker DJ (1998) Mothers, babies, and health in later life. Churchill Livingstone, London

    Google Scholar 

  • Barreau F, Ferrier L, Fioramonti J, Bueno L (2004) Neonatal maternal deprivation triggers long term alterations in colonic epithelial barrier and mucosal immunity in rats. Gut 53:501–506

    PubMed  Google Scholar 

  • Bhansali P, Dunning J, Singer SE, David L, Schmauss C (2007) Early life stress alters adult serotonin 2C receptor pre-mRNA editing and expression of the alpha subunit of the heterotrimeric G-protein G q. J Neurosci 27:1467–1473

    PubMed  Google Scholar 

  • Biondi M, Zannino LG (1997) Psychological stress, neuroimmunomodulation, and susceptibility to infectious disease in animals and man: a review. PNAS 93:3043–3047

    Google Scholar 

  • Borrow P, Tonks P, Welsh CJR, Nash AA (1992) The role of CD8+ T cells in the acute and chronic phases of Theiler’s virus-induced disease in mice. J Gen Virol 73:1861–1865

    PubMed  Google Scholar 

  • Boynton-Jarrett R, Ryan LM, Berkman LF, Wright RJ (2008) Cumulative violence exposure and self-rated health: longitudinal study of adolescents in the United States. Pediatrics 122:961–970

    PubMed  Google Scholar 

  • Brunson KL, Eghbal-Ahmadi M, Bender R, Chen Y, Baram TZ (2001) Long-term, progressive hippocampal cell loss and dysfunction induced by early-life administration of corticotropin-releasing hormone reproduce the effects of early-life stress. Proc Natl Acad Sci USA 98:8856–8861

    PubMed  Google Scholar 

  • Bukilica M, Djordjevic S, Maric I, Dimitrijevic M, Markovic BM, Jankovic BD (1991) Stress-induced suppression of experimental allergic encephalomyelitis in the rat. Int J Neurosci 59:167–175

    PubMed  Google Scholar 

  • Caldji C, Francis D, Tannenbaum B, Sharma S, Meaney MJ (1998) Maternal care in infancy influences the development of neural systems mediating fearfulness in the rat. PNAS 95:5335–5340

    PubMed  Google Scholar 

  • Caldji C, Diorio J, Meaney MJ (2000a) Variations in maternal care in infancy regulate the development of stress reactivity. Biol Psychiatry 48:1164–1174

    PubMed  Google Scholar 

  • Caldji C, Francis D, Sharma S, Plotsky PM, Meaney MJ (2000b) The effects of early rearing environment on the development of GABAA and central benzodiazepine receptor levels and novelty-induced fearfulness in the rat. Neuropsychopharmacology 22:219–229

    PubMed  Google Scholar 

  • Campbell T, Meagher MW, Sieve A, Scott B, Storts R, Welsh TH, Welsh CJR (2001) The effects of restraint stress on the neuropathogenesis of Theiler’s virus-induced demyelination. I. Acute disease. Brain Behav Immun 15:235–254

    PubMed  Google Scholar 

  • Capitanio JP, Lerche NW (1991) Psychosocial factors and disease progression in simian AIDS: a preliminary report. AIDS 5:1103–1106

    PubMed  Google Scholar 

  • Catalani A, Casolini P, Scaccianoce S, Patacchioli FR, Spinozzi P, Angelucci L (2000) Maternal corticosterone during lactation permanently affects brain corticosteroid receptors, stress response and behaviour in rat progeny. Neuroscience 100:319–325

    PubMed  Google Scholar 

  • Choleris E, Thomas AW, Kavaliers M, Prato FS (2001) A detailed ethological analysis of the mouse open field test: effects of diazepam, chlordiazepoxide and an extremely low frequency pulsed magnetic field. Neurosci Biobehav Rev 25:235–260

    PubMed  Google Scholar 

  • Coe CL, Lubach GR (2003) Critical periods of special health relevance for psychoneuroimmunology. Brain Behav Immun 12:3–12

    Google Scholar 

  • Coe CL, Lubach GR, Schneider ML, Dierschke DJ, Ershler WB (1992) Early rearing conditions alter immune responses in the developing infant primate. Pediatrics 90:505–509

    PubMed  Google Scholar 

  • Craft T, Zhang N, Glasper E, Hurn P, DeVries A (2006) Neonatal factors influence adult stroke outcome. Psychoneuroendocrinology 31:601–613

    PubMed  Google Scholar 

  • Danese A, Pariante CM, Caspi A, Taylor A, Poulton R (2007) Childhood maltreatment predicts adult inflammation in a life-course study. PNAS 104:1319–1324

    PubMed  Google Scholar 

  • DeBellis MD, Baum AS, Birmaher B, Keshavan MS, Eccard CH, Boring AM, Jenkins FJ, Ryan ND (1999) Developmental traumatology part I: biological stress systems. Biol Psychiatry 45:1259–1270

    Google Scholar 

  • Denenberg VH (1999) Commentary: is maternal stimulation the mediator of the handling effect in infancy. Dev Psychobiol 34:1–3

    PubMed  Google Scholar 

  • Denenberg VH, Ottinger DR, Stephens MW (1962) Effects of maternal factors upon growth and behavior of the rat. Child Dev 33:65–71

    PubMed  Google Scholar 

  • Dong M, Dube SR, Felitti VJ, Giles WH, Anda RF (2003) Adverse childhood experiences and self-reported liver disease: new insights into the causal pathway. Arch Intern Med 163:1949–1956

    PubMed  Google Scholar 

  • Dong M, Giles WH, Felitti VJ, Dube SR, Williams JE, Chapman DP, Anda RF (2004) Insights into causal pathways for ischemic heart disease: adverse childhood experiences study. Circulation 110:1761–1766

    PubMed  Google Scholar 

  • Dowdell KC, Gienapp IE, Stuckman S, Wardrop RM, Whitacre CC (1999) Neuroendocrine modulation of chronic relapsing experimental autoimmune encephalomyelitis: a critical role for the hypothalamic-pituitary-adrenal axis. J Neuroimmunol 100:243–251

    PubMed  Google Scholar 

  • Dube SR, Fairweather D, Pearson WS, Felitti VJ, Anda RF, Croft JB (2009) Cumulative childhood stress and autoimmune diseases in adults. Psychosom Med 71:243–250

    PubMed  Google Scholar 

  • Fazekas F, Offenbacher H, Fuchs S (1988) Criteria for an increased specificity of MRI interpretation in elderly subjects with suspected multiple sclerosis. Neurology 38:1822–1825

    PubMed  Google Scholar 

  • Felitti VJ, Anda RF, Nordenberg D, Williamson DF, Spitz AM, Edwards V, Koss MP, Marks JS (1998) Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults: the adverse childhood experiences study. Am J Prev Med 14:245–258

    PubMed  Google Scholar 

  • Francis DD, Caldji C, Champagne F, Plotsky PM, Meaney MJ (1999a) The role of corticotropin-releasing factor–norepinephrine systems in mediating the effects of early experience on the development of behavioral and endocrine responses to stress. Biol Psychiatry 46:1153–1166

    PubMed  Google Scholar 

  • Francis DD, Champagne FA, Liu D, Meaney MJ (1999b) Maternal care, gene expression, and the development of individual differences in stress reactivity. Ann N Y Acad Sci 896:66–84

    PubMed  Google Scholar 

  • French Research Group on Multiple Sclerosis (1992) Multiple sclerosis in 54 twinships: concordance rate is independent of zygosity. Ann Neurol 32:724–727

    Google Scholar 

  • Grant J, Brown GW, Harris T (1989) Severely threatening events and marked life difficulties preceding the onset or exacerbation of multiple sclerosis. J Neurol Neurosurg Psychiatry 52:8–13

    PubMed  Google Scholar 

  • Griffin AC, Whitacre CC (1990) Differential effects of stress on disease outcome in experimental allergic encephalomyelitis. FASEB J 4:2038

    Google Scholar 

  • Griffin A, Lo W, Wolny A, Whitacre C (1993) Suppression of experimental autoimmune encephalomyelitis by restraint stress: sex differences. J Neuroimmunol 44:103–116

    PubMed  Google Scholar 

  • Hawks BW, Plotsky SJ, Garlow SJ (1999) Mouse strain differences in behavior and corticosterone in response to early postnatal separation. Soc Neurosci Abs 25:616

    Google Scholar 

  • Herman JP, Cullinan WE (1997) Neurocircuitry of stress: central control of the hypothalamic-pituitary-adrenal axis. Trends Neurosci 20:78–84

    PubMed  Google Scholar 

  • Hernan MA, Zhang SM, Lipworth L, Olek MJ, Ascherio A (2001) Multiple sclerosis and age at infection with common viruses. Epidemiology 12:301–306

    PubMed  Google Scholar 

  • Hodgson DM, Knott B (2002) Potentiation of tumor metastasis in adulthood by neonatal endoxotin exposure: sex differences. Psychoneuroendocrinology 27:791–798

    PubMed  Google Scholar 

  • Huot RL, Gonzalez ME, Ladd CO, Thrivikraman KV, Plotsky PM (2004) Foster litters prevent hypothalamic-pituitary-adrenal axis sensitization mediated by neonatal maternal separation. Psychoneuroendocrinology 29:279–289

    PubMed  Google Scholar 

  • Jilek S, Schluep M, Meylan P, Vingerhoets F, Guignard L, Monney A, Kleeberg J, Goff GL, Pantaleo G, Du Pasquier RA (2008) Strong EBV-specific CD8+ T-cell response in patients with early multiple sclerosis. Brain 131:1712–1721

    PubMed  Google Scholar 

  • Johnson RR, Storts R, Welsh TH Jr, Welsh CJ, Meagher MW (2004) Social stress alters the severity of acute Theiler’s virus infection. J Neuroimmunol 148:74–85

    PubMed  Google Scholar 

  • Johnson RR, Prentice TW, Bridegam P, Young CR, Steelman AJ, Welsh TH, Welsh CJR, Meagher MW (2006) Social stress alters the severity and onset of the chronic phase of Theiler’s virus infection. J Neuroimmunol 175:39–51

    PubMed  Google Scholar 

  • Kalinichev M, Easterling KW, Plotsky PM, Holtzman SG (2002) Long-lasting changes in stress-induced corticosterone response and anxiety-like behaviors as a consequence of neonatal maternal separation in Long-Evans rats. Pharmacol Biochem Behav 73:131–140

    PubMed  Google Scholar 

  • Kurtzke JF, Hyllested K, Heltberg A (1995) Multiple sclerosis in the Faroe Islands: transmission across four epidemics. Acta Neurol Scand 91:321–332

    PubMed  Google Scholar 

  • Laban O, Dimitrijevic M, von Hoersten S, Markovic BM, Jankovic BD (1995a) Experimental allergic encephalomyelitis in adult DA rats subjected to neonatal handling or gentling. Brain Res 676:133–140

    PubMed  Google Scholar 

  • Laban O, Markovic BM, Dimitrijevic M, Jankovic BD (1995b) Maternal deprivation and early weaning modulated experimental allergic encephalomyelitis in the rat. Brain Behav Immun 9:9–19

    PubMed  Google Scholar 

  • Ladd CO, Huot RL, Thrivikraman KV, Nemeroff CB, Meaney MJ, Plotsky PM (2000) Long-term behavioral and neuroendocrine adaptations to adverse early experience. Prog Brain Res 122:81–103

    PubMed  Google Scholar 

  • Ladd CO, Owens MJ, Nemeroff CB (1996) Persistent changes in corticotropin-releasing factor neuronal systems induced by maternal deprivation. Endocrinology 137:1212–1218

    PubMed  Google Scholar 

  • Laroche J, Gasbarro L, Herman JP, Blaustein JD (2009) Enduring influences of peripubertal/adolescent stressors on behavioral response to estradiol and progesterone in adult female mice. Endocrinology 150:3717–3725

    PubMed  Google Scholar 

  • Laudenslager ML, Capitanio JP, Reite M (1985) Possible effects of early separation experiences on subsequent immune function in adult macaque monkeys. Am J Psychiatry 142:862–864

    PubMed  Google Scholar 

  • Levine S (1957) Infantile experience to physiological stress. Science 126:405–406

    Google Scholar 

  • Levine S, Saltzman A (1987) Nonspecific stress prevents relapses of experimental allergic encephalomyelitis in rats. Brain Behav Immun 1:336–341

    PubMed  Google Scholar 

  • Levine S, Strebel R, Wenk E, Harman P (1962) Suppression of experimental autoimmune encephalomyelitis by stress. Exp Biol Med 109:294–298

    Google Scholar 

  • Lewis MH, Gluck JP, Petitto JM, Hensley LL, Ozer H (2000) Early social deprivation in nonhuman primates: long-term effects on survival and cell-mediated immunity. Biol Psychiatry 47:119–126

    PubMed  Google Scholar 

  • Lipton HL (1975) Theiler’s virus infection in mice: an unusual biphasic disease process leading to demyelination. Infect Immun 11:1147–1155

    PubMed  Google Scholar 

  • Liu D, Diorio J, Tannenbaum B, Caldji C, Francis D, Freedman A, Sharma S, Pearson D, Plotsky PM, Meaney MJ (1997) Maternal care, hippocampal glucocorticoid receptors, and hypothalamic-pituitary-adrenal responses to stress. Science 277(12):1659–1662

    PubMed  Google Scholar 

  • Liu D, Caldji C, Sharma S, Plotsky PM, Meaney MJ (2000) Influence of neonatal rearing conditions on stress-induced adrenocorticotropin responses and norepinephrine release in the hypothalamic paraventricular nucleus. J Neuroendocrinol 12:5–12

    PubMed  Google Scholar 

  • Lubach GR, Coe CL, Ershler WB (1995) Effects of early rearing environment on immune responses of infant rhesus monkeys. Brain Behav Immun 9:31–46

    PubMed  Google Scholar 

  • Maier SF, Watkins LR (1998) Cytokines for psychologists: implications of bidirectional communication for understanding behavior, mood, and cognition. Psychol Rev 105:85–107

    Google Scholar 

  • Marchetti B, Morale MC, Testa N, Tirolo C, Caniglia S, Amor A, Dijkstra CD, Barden N (2001) Stress, the immune system and vulnerability to degenerative disorders of the central nervous system in transgenic mice expressing glucocorticoid receptor antisense RNA. Brain Res Rev 37:259–272

    PubMed  Google Scholar 

  • McGavern DB, Zoecklein L, Drescher KM, Rodriguez M (1999) Quantitative assessment of neurological deficits in a chronic progressive murine model of CNS demyelination. Exp Neurol 158:171–181

    PubMed  Google Scholar 

  • Meagher MW, Johnson RR, Young EE, Vichaya EG, Harden A, Connor M, Welsh CJR (2007a) Interleukin-6 as a mechanism for the adverse effects of SDR on acute TMEV Infection. Brain Behav Immun 21:1083–1095

    PubMed  Google Scholar 

  • Meagher MW, Johnson RR, Vichaya EG, Young EE, Lunt S, Welsh CJR (2007b) Social conflict exacerbates an animal model of multiple sclerosis. Trauma Violence Abuse 8:314–330

    PubMed  Google Scholar 

  • Meagher MW, Sieve AN, Johnson RR, Satterlee D, Johnson RR, Storts R, Welsh TH, Welsh CJR (in revision) Early life stress interacts with later restraint stress to alter CNS inflammation and endocrine responses during infection in adult mice

  • Meaney MJ (2001) Maternal care, gene expression, and the transmission of individual differences in stress reactivity across generations. Annu Rev Neurosci 24:1161–1192

    PubMed  Google Scholar 

  • Meaney MJ, Aitken DH (1985) The effects of early postnatal handling on hippocampal glucocorticoid receptor concentrations: temporal parameters. Brain Res 354:301–304

    PubMed  Google Scholar 

  • Meaney MJ, Diorio J, Francis D, Widdowson J, LaPlanta P, Caldji C, Sharma S, Seckl JS, Plotsky PM (1996) Early environmental regulation of forebrain glucocorticoid receptor gene expression: implications for adrenocortical responses to stress. Dev Neurosci 18:49–72

    PubMed  Google Scholar 

  • Meaney MJ, Diorio J, Francis D, Weaver S, Yau J, Chapman K, Seckl JR (2000) Postnatal handling increases the expression of cAMP-inducible transcription factors in the rat hippocampus: the effects of thyroid hormones and serotonin. J Neurosci 20:3926–3935

    PubMed  Google Scholar 

  • Melchior M, Moffitt TE, Milne BJ, Poulton R, Caspi A (2007) Why do children from socioeconomically disadvantaged families suffer from poor health when they reach adulthood? A life-course study. Am J Epidemiol 166:966–974

    PubMed  Google Scholar 

  • Mi W, Belyavskyi M, Johnson RR, Sieve AN, Meagher MW, Welsh CJR (2004) Alterations in chemokine expression following Theiler’s virus infection and restraint stress. J Neuroimmunol 178:59–61

    Google Scholar 

  • Mi W, Prentice TW, Young CR, Johnson RR, Sieve AN, Meagher MW, Welsh CJR (2006a) Restraint stress decreases virus-induced pro-inflammatory cytokine expression during acute Theiler’s virus infection. J Neuroimmunol 178:49–61

    PubMed  Google Scholar 

  • Mi W, Young CR, Storts R, Steelman A, Meagher MW, Welsh CJR (2006b) Stress alters pathogenicity and facilitates systemic dissemination of Theiler’s virus. Microb Pathog 41:133–143

    PubMed  Google Scholar 

  • Millstein RA, Holmes A (2007) Effects of repeated maternal separation on anxiety- and depression-related phenotypes in different mouse strains. Neurosci Biobehav Rev 31:3–17

    PubMed  Google Scholar 

  • Millstein RA, Ralph RJ, Yang RJ, Holmes A (2006) Effects of repeated maternal separation on prepulse inhibition of startle across inbred mouse strains. Genes Brain Behav 5:346–354

    PubMed  Google Scholar 

  • Mohr DC, Goodkin DE, Bacchetti P, Boudewyn AC, Huang L, Marrietta P, Cheuk W, Dee B (2000) Psychological stress and the subsequent appearance of new brain MRI lesions in MS. Neurology 55:55–61

    PubMed  Google Scholar 

  • Nicholson SM, Peterson JD, Miller SD, Wang K, Dal Canto MC, Melvold RW (1994) BALB/c substrain differences in susceptibility to Theiler’s murine encephalomyelitis virus-induced demyelinating disease. J Neuroimmunol 52:19–24

    PubMed  Google Scholar 

  • Njenga MK, Asakura K, Hunter SF, Wettstein P, Pease LR, Rodriguez M (1997) The immune system preferentially clears Theiler’s virus from the gray matter of the central nervous system. J Virol 71:8592–8601

    PubMed  Google Scholar 

  • O’Mahony SM, Marchesi JR, Scully P, Codling C, Ceolho AM, Quigley EMM, Cryan JF, Dinan TG (2009) Early life stress alters behavior, immunity, and microbiota in rats: implications for irritable bowel syndrome and psychiatric illnesses. Biol Psychiatry 65:263–267

    PubMed  Google Scholar 

  • Parfitt DB, Levin JK, Saltstein KP, Klayman AS, Greer LM, Helmreich DL (2004) Differential early rearing environments can accentuate or attenuate the responses to stress in male C57BL/6 mice. Brain Res 1016:111–118

    PubMed  Google Scholar 

  • Parfitt DB, Walton JR, Corriveau EA, Helmreich DL (2007) Early life stress effects on adult stress-induced corticosterone secretion and anxiety-like behavior in the C57BL/6 mouse are not as robust as initially thought. Horm Behav 52:417–426

    PubMed  Google Scholar 

  • Plotsky PM, Meaney MJ (1993) Early, postnatal experience alters hypothalamic corticotropin-releasing factor (CRF) mRNA, median eminence CRF content and stress-induced release in adult rats. Brain Res Mol Brain Res 18:195–200

    PubMed  Google Scholar 

  • Plotsky PM, Thrivikraman KV, Meaney MJ (1993) Central and feedback regulation of hypothalamic corticotropin-releasing factor secretion. Ciba Found Symp 172:59–84

    PubMed  Google Scholar 

  • Plotsky PM, Thrivikraman KV, Nemeroff CB, Caldji C, Sharma S, Meaney MJ (2005) Long-term consequences of neonatal rearing on central corticotropin-releasing factor systems in adult male rat offspring. Neuropsychopharmacology 30:2192–2204

    PubMed  Google Scholar 

  • Pryce CR, Bettschen D, Feldon J (2001) Comparison of the effects of early handling and early deprivation on maternal care in the rat. Dev Psychobiol 38:239–251

    PubMed  Google Scholar 

  • Romeo RD, Mueller A, Sisti HM, Ogawa S, McEwen BS, Brake WG (2003) Anxiety and fear behaviors in adult male and female C57BL/6 mice are modulated by maternal separation. Horm Behav 43:561–567

    PubMed  Google Scholar 

  • Romeo RD, Fossella JA, Bateup HS, Sisti HM, Brake WG, McEwen BS (2004) Maternal separation suppresses TGF alpha mRNA expression in the prefrontal cortex of male and female neonatal C57BL/6 mice. Brain Res Dev Brain Res 152:73–77

    PubMed  Google Scholar 

  • Sadovnick A, Ebers G, Dyment D et al (1996) Evidence for the genetic basis of multiple sclerosis. Lancet 347:1728–1730

    PubMed  Google Scholar 

  • Sanchez MM, Ladd CO, Plotsky PM (2001) Early adverse experience as a developmental risk factor for later psychopathology: evidence from rodent and primate models. Dev Psychopathol 13:419–449

    PubMed  Google Scholar 

  • Schmidt M, Oitzl MS, Levine S, de Kloet R (2002) The HPA system during postnatal development of CD1 mice and the effects of maternal deprivation. Brain Res Dev Brain Res 139:39–49

    PubMed  Google Scholar 

  • Schmidt MV, Enthoven L, van der Mark M, Levine S, de Kloet ER, Oitzl MS (2003) The postnatal development of the hypothalamic-pituitary-adrenal axis in the mouse. Int J Dev Neurosci 21:125–132

    PubMed  Google Scholar 

  • Seckl JR (1997) Glucocorticoids, fetoplacental 11-hyrdoxysteroid dehydrogenase type 2 and the early life origins of adult disease. Steroids 62:89–94

    PubMed  Google Scholar 

  • Selye H (1936) Thymus and adrenals in the responses of organisms to injuries and intoxications. Br J Exp Pathol 17:234–248

    Google Scholar 

  • Sibley WA (1997) Risk factors in multiple sclerosis. In: Raine CS, McFarland HF, Tortellotte WW (eds) Multiple sclerosis: clinical and pathogenetic basis. Chapman & Hall, London, pp 141–148

    Google Scholar 

  • Sieve AN, Steelman D, Storts R, Young CR, Welsh TH, Welsh CJR, Meagher MW (2004) Chronic restraint stress during early infection exacerbates the subsequent demyelinating phase of Theiler’s virus infection. J Neuroimmunol 155:103–118

    PubMed  Google Scholar 

  • Sieve AN, Steelman AJ, Young CR, Storts R, Welsh TH, Welsh CJR, Meagher MW (2006) Sex-dependent effects of chronic restraint stress during early Theiler’s virus infection on the subsequent demyelinating disease in CBA mice. J Neuroimmunol 177:46–62

    PubMed  Google Scholar 

  • Sospedra M, Martin R (2005) Immunology of multiple sclerosis. Annu Rev Immunol 23:683–747

    PubMed  Google Scholar 

  • Steelman AJ, Dean DD, Young CR, Smith R, Prentice TW, Meagher MW, Welsh CJR (2009) Restraint stress modulates virus specific adaptive immunity during acute Theiler’s virus infection. Brain Behav Immun 23:830–843

    PubMed  Google Scholar 

  • Stephan M, Straub RH, Breivik T, Pabst R, von Hörsten S (2002) Postnatal maternal deprivation aggravates experimental autoimmune encephalomyelitis in adult Lewis rats: reversal by chronic imipramine treatment. Int J Dev Neurosci 20:125–132

    PubMed  Google Scholar 

  • Sternberg E, Hill J, Chrousos G, Kamilaris T, Listwak S, Gold P, Wilder R (1989) Inflammatory mediator-induced hypothalamic–pituitary–adrenal axis activation is defective in streptococcal cell wall arthritis-susceptible Lewis rats. Proc Natl Acad Sci USA 86:2374–2378

    PubMed  Google Scholar 

  • Teunis MAT, Heijnen CJ, Sluyter F, Bakker JM, Van Dam AMW, Hof M, Cools AR, Kavelaars A (2002) Maternal deprivation of rat pups increases clinical symptoms of experimental autoimmune encephalomyelitis at adult age. J Neuroimmunol 133:30–38

    PubMed  Google Scholar 

  • Veenema AH, Bredewolda R, Neumanna ID (2007) Opposite effects of maternal separation on intermale and maternal aggression in C57BL/6 mice: link to hypothalamic vasopressin and oxytocin immunoreactivity. Psychoneuroendocrinology 32:437–450

    PubMed  Google Scholar 

  • Walker EA, Gelfand A, Katon WJ, Koss MP, von Korff M, Bernstein D, Russo J (1999) Adult health status of women with histories of childhood abuse and neglect. Am J Med 107:332–339

    PubMed  Google Scholar 

  • Warren S, Greenhill S, Warren KG (1982) Emotional stress and the development of multiple sclerosis: case-control evidence of a relationship. J Chronic Dis 35:821–831

    PubMed  Google Scholar 

  • Welsh CJR, Tonks P, Nash AA, Blakemore WF (1987) The effect of L3T4 T cell depletion on the pathogenesis of Theiler’s murine encephalomyelitis virus infection in CBA mice. J Gen Virol 68:1659–1667

    PubMed  Google Scholar 

  • Welsh CJR, Blakemore WF, Tonks P, Borrow P, Nash AA (1989) Theiler’s murine encephalomyelitis virus infection in mice: a persistent viral infection of the central nervous system which induces demyelination. In: Dimmock N (ed) Immune responses, virus infection and disease. Oxford University Press, Oxford, pp 125–147

    Google Scholar 

  • Welsh CJ, Bustamante L, Nayak M, Welsh TH, Dean DD, Meagher MW (2004) The effects of restraint stress on the neuropathogenesis of Theiler’s virus infection II: NK cell function and cytokine levels in acute disease. Brain Behav Immun 18:166–174

    PubMed  Google Scholar 

  • Whishaw I, Metz G, Kolb B, Pellis S (2001) Accelerated nervous system development contributes to behavioral efficiency in the laboratory mouse: a behavioral review and theoretical proposal. Dev Psychobiol 39:151–170

    PubMed  Google Scholar 

  • Whitacre CC, Dowdell K, Griffin AC (1998) Neuroendocrine influences on experimental autoimmune encephalomyelitis. Ann N Y Acad Sci 840:705–716

    PubMed  Google Scholar 

  • Wigger A, Neumann ID (1999) Periodic maternal deprivation induces gender-dependent alterations in behavioral and neuroendocrine responses to emotional stress in adult rats. Physiol Behav 66:293–302

    PubMed  Google Scholar 

  • Willer C, Dyment D, Risch N et al (2003) Twin concordance and sibling recurrence rate in multiple sclerosis. Proc Natl Acad Sci 100:12877–12882

    PubMed  Google Scholar 

  • Young EE, Prentice TW, Satterlee D, McCullough H, Sieve AN, Johnson RR, Welsh TH, Welsh CJR, Meagher MW (2008) Glucocorticoid exposure alters the pathogenesis of Theiler’s murine encephalomyelitis virus during acute infection. Physiol Behav 95:63–71

    PubMed  Google Scholar 

  • Young EE, Sieve AN, Vichaya EG, Young CR, Ambrus A, Storts R, Welsh CJR, Meagher MW (in press) Chronic restraint stress during early Theiler’s virus infection exacerbates the subsequent demyelinating disease in SJL mice: II. Histological evaluation of CNS disease severity. J Neuroimmunol

Download references

Acknowledgments

This research was funded by grants from the National Multiple Sclerosis Society RG-3128 and NIH/NINDS R01-NS39569 to C.J.W. and M.W.M and by NIH/NINDS R01-NS060822 awarded to M.W.M. and C.J. W. We would also like to thank Heath McCullough and Patrick Bridegam for their help in conducting the maternal separation procedures and data management.

Author information

Authors and Affiliations

  1. Department of Psychology, College of Liberal Arts, Texas A&M University, College Station, TX, 77843-4235, USA

    M. W. Meagher, A. N. Sieve, R. R. Johnson, D. Satterlee & T. W. Prentice

  2. Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, USA

    M. Belyavskyi, W. Mi, T. H. Welsh Jr. & C. J. R. Welsh

  3. Department of Animal Science, College of Agriculture and Life Sciences, Texas A&M University, College Station, TX, USA

    T. H. Welsh Jr.

Authors
  1. M. W. Meagher
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. N. Sieve
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R. R. Johnson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. D. Satterlee
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Belyavskyi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. W. Mi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. T. W. Prentice
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. T. H. Welsh Jr.
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. C. J. R. Welsh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. W. Meagher.

Additional information

Edited by Kristen Jacobson.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Meagher, M.W., Sieve, A.N., Johnson, R.R. et al. Neonatal Maternal Separation Alters Immune, Endocrine, and Behavioral Responses to Acute Theiler’s Virus Infection in Adult Mice. Behav Genet 40, 233–249 (2010). https://doi.org/10.1007/s10519-010-9333-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10519-010-9333-5

Keywords

Search

Navigation