Neonatal Immune Activation May Provoke Long-term Depressive Attributes

Author(s): Simone H. Schelder-Marzzani, Paula Dias, Viviane Freiberger, Letícia Ventura, Bruna B. Silva, Matheus L. Dutra, Franciane Bobinski, Aline D. Schlindwein, Omar J. Cassol, Clarissa M. Comim*.

Journal Name: Current Neurovascular Research

Volume 16 , Issue 4 , 2019

Become EABM
Become Reviewer

Abstract:

Background: Studies have shown the relationship between neuroinflammation and depressive- like parameters. However, research still has not been carried out to evaluate neuroinflammation in the neonatal period and psychiatric disorders in adulthood.

Objective: To verify the association between neonatal immune activation and depressive-like parameters in adulthood using an animal model.

Methods: Two days old C57BL/6 animals were exposed to lipopolysaccharides (LPS) or phosphate- buffered saline (PBS). When the animals were 46 days old, they received PBS or Imipramine at 14 days. At 60 days, the consumption of sucrose; immobility time; adrenal gland and the hippocampus weight; levels of plasma corticosterone and hippocampal Brain-derived neurotrophic factor (BDNF) were evaluated.

Results: It was observed that the animals exposed to LPS in the neonatal period and evaluated in adulthood decreased the consumption of sucrose and had reducted hippocampus weight. Also, the exposed animals presented an increase of immobility time, adrenal gland weight and plasma levels of corticosteroids. The use of imipramine did not only modify the decreased hippocampal weight. On the other hand, there were no alterations in the BDNF levels in the hippocampus with or without the use of imipramine.

Conclusion: These results suggest that neonatal immune activation may be associated with depressive- like parameters in adulthood. It is believed that endotoxemia may trigger physiological and behavioral alterations, increasing vulnerability for the development of depression in adulthood.

Keywords: Endotoxemia, Major Depressive Disorder (MDD), depression-like behavior, inflammation, neurodevelopment, Brain-derived Neurotrophic Factor (BDNF).

[1]
Ormel J, Kessler RC, Schoevers R. Depression: More treatment but no drop in prevalence: How effective is treatment? And can we do better? Curr Opin Psychiatry 2019; 32(4): 348-54.
[PMID: 30855297]
[2]
Baune BT, Miller R, McAfoose J, Johnson M, Quirk F, Mitchell D. The role of cognitive impairment in general functioning in major depression. Psychiatry Res 2010; 176(2-3): 183-9.
[http://dx.doi.org/10.1016/j.psychres.2008.12.001] [PMID: 20138370]
[3]
Jeon SW, Kim YK. Inflammation-induced depression: Its pathophysiology and therapeutic implications. J Neuroimmunol 2017; 313: 92-8.
[http://dx.doi.org/10.1016/j.jneuroim.2017.10.016] [PMID: 29153615]
[4]
Altamura AC, Dell’osso B, Vismara S, Mundo E. May duration of untreated illness influence the long-term course of major depressive disorder? Eur Psychiatry 2008; 23(2): 92-6.
[http://dx.doi.org/10.1016/j.eurpsy.2007.11.004] [PMID: 18248964]
[5]
Valkanova V, Ebmeier KP, Allan CL. CRP, IL-6 and depression: A systematic review and meta-analysis of longitudinal studies. J Affect Disord 2013; 150(3): 736-44.
[http://dx.doi.org/10.1016/j.jad.2013.06.004] [PMID: 23870425]
[6]
Flint J, Kendler KS. The genetics of major depression. Neuron 2014; 81(3): 484-503.
[http://dx.doi.org/10.1016/j.neuron.2014.01.027] [PMID: 24507187]
[7]
Wilkowska A, Pikuła M, Rynkiewicz A, Wdowczyk-Szulc J, Trzonkowski P, Landowski J. Increased plasma pro-inflammatory cytokine concentrations after myocardial infarction and the presence of depression during next 6-months. Psychiatr Pol 2015; 49(3): 455-64.
[http://dx.doi.org/10.12740/PP/33179] [PMID: 26276914]
[8]
Uguz F, Akman C, Kucuksarac S, Tufekci O. Anti-tumor necrosis factor-alpha therapy is associated with less frequent mood and anxiety disorders in patients with rheumatoid arthritis. Psychiatry Clin Neurosci 2009; 63(1): 50-5.
[http://dx.doi.org/10.1111/j.1440-1819.2008.01905.x] [PMID: 19154212]
[9]
Cattaneo A, Macchi F, Plazzotta G, et al. Inflammation and neuronal plasticity: A link between childhood trauma and depression pathogenesis. Front Cell Neurosci 2015; 31(9): 40.
[http://dx.doi.org/10.3389/fncel.2015.00040]
[10]
Rawdin BJ, Mellon SH, Dhabhar FS, et al. Dysregulated relationship of inflammation and oxidative stress in major depression. Brain Behav Immun 2013; 31: 143-52.
[http://dx.doi.org/10.1016/j.bbi.2012.11.011] [PMID: 23201587]
[11]
He H, Geng T, Chen P, et al. NK cells promote neutrophil recruitment in the brain during sepsis-induced neuroinflammation. Sci Rep 2016; 6: 27711.
[http://dx.doi.org/10.1038/srep27711] [PMID: 27270556]
[12]
Slavich GM, Irwin MR. From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. Psychol Bull 2014; 140(3): 774-815.
[http://dx.doi.org/10.1037/a0035302] [PMID: 24417575]
[13]
Carvalho LA, Bergink V, Sumaski L, et al. Inflammatory activation is associated with a reduced glucocorticoid receptor alpha/beta expression ratio in monocytes of inpatients with melancholic major depressive disorder. Transl Psychiatry 2014; 2014 4e344
[http://dx.doi.org/10.1038/tp.2013.118] [PMID: 24424390]
[14]
Felger JC, Lotrich FE, Francis E. Inflammatory cytokines in depression: Neurobiological mechanisms and therapeutic implications. Neuroscience 2013; 246: 199-229.
[http://dx.doi.org/10.1016/j.neuroscience.2013.04.060] [PMID: 23644052]
[15]
Comim CM, Cassol OJ Jr, Constantino LC, et al. Depressive-like parameters in sepsis survivor rats. Neurotox Res 2010; 17(3): 279-86.
[http://dx.doi.org/10.1007/s12640-009-9101-6] [PMID: 19705213]
[16]
Cunningham C, Campion S, Lunnon K, et al. Systemic inflammation induces acute behavioral and cognitive changes and accelerates neurodegenerative disease. Biol Psychiatry 2009; 65(4): 304-12.
[http://dx.doi.org/10.1016/j.biopsych.2008.07.024] [PMID: 18801476]
[17]
Menshanov PN, Lanshakov DA, Dygalo NN. proBDNF is a major product of bdnf gene expressed in the perinatal rat cortex. Physiol Res 2015; 64(6): 925-34.
[PMID: 26047381]
[18]
Cardoso FL, Herz J, Fernandes A, et al. Systemic inflammation in early neonatal mice induces transient and lasting neurodegenerative effects. J Neuroinflammation 2015; 29(12): 82.
[19]
Singh K, Zhang LX, Bendelja K, et al. Inter-alpha inhibitor protein administration improves survival from neonatal sepsis in mice. Pediatr Res 2010; 68(3): 242-7.
[http://dx.doi.org/10.1203/PDR.0b013e3181e9fdf0] [PMID: 20520583]
[20]
Comim CM, Bussmann RM, Simão SR, et al. Experimental neonatal sepsis causes long-term cognitive impairment. Mol Neurobiol 2016; 53(9): 5928-34.
[http://dx.doi.org/10.1007/s12035-015-9495-5] [PMID: 26510743]
[21]
Porsolt RD. Animal model of depression. Biomedicine (Paris) 1979; 30(3): 139-40.
[PMID: 573643]
[22]
Sakić B, Szechtman H, Braciak T, Richards C, Gauldie J, Denburg JA. Reduced preference for sucrose in autoimmune mice: A possible role of interleukin-6. Brain Res Bull 1997; 44(2): 155-65.
[http://dx.doi.org/10.1016/S0361-9230(97)00107-X] [PMID: 9292205]
[23]
Ménard C, Pfau ML, Hodes GE, Russo SJ. Immune and neuroendocrine mechanisms of stress vulnerability and resilience. Neuropsychopharmacology 2017; 42(1): 62-80.
[http://dx.doi.org/10.1038/npp.2016.90] [PMID: 27291462]
[24]
Pizzagalli DA. Depression, stress, and anhedonia: Toward a synthesis and integrated model. Annu Rev Clin Psychol 2014; 10: 393-423.
[http://dx.doi.org/10.1146/annurev-clinpsy-050212-185606] [PMID: 24471371]
[25]
Miller AH, Raison CL. The role of inflammation in depression: From evolutionary imperative to modern treatment target. Nat Rev Immunol 2016; 16(1): 22-34.
[http://dx.doi.org/10.1038/nri.2015.5] [PMID: 26711676]
[26]
Lucca G, Comim CM, Valvassori SS, et al. Chronic mild stress paradigm reduces sweet food intake in rats without affecting brain derived neurotrophic factor protein levels. Curr Neurovasc Res 2008; 5(4): 207-13.
[http://dx.doi.org/10.2174/156720208786413406] [PMID: 18991655]
[27]
Chadman KK, Yang M, Crawley JN. Criteria for validating mouse models of psychiatric diseases. Am J Med Genet B Neuropsychiatr Genet 2009; 150B(1): 1-11.
[http://dx.doi.org/10.1002/ajmg.b.30777] [PMID: 18484083]
[28]
Réus GZ, Stringari RB, Ribeiro KF, et al. Maternal deprivation induces depressive-like behaviour and alters neurotrophin levels in the rat brain. Neurochem Res 2011; 36(3): 460-6.
[http://dx.doi.org/10.1007/s11064-010-0364-3] [PMID: 21161589]
[29]
Nestler EJ, Hyman SE. Animal models of neuropsychiatric disorders. Nat Neurosci 2010; 13(10): 1161-9.
[http://dx.doi.org/10.1038/nn.2647] [PMID: 20877280]
[30]
Lawson MA, McCusker RH, Kelley KW. Interleukin-1 beta converting enzyme is necessary for development of depression-like behavior following intracerebroventricular administration of lipopolysaccharide to mice. J Neuroinflammation 2013; 1(10): 54.
[31]
Ellis S, Mouihate A, Pittman QJ. Neonatal programming of the rat neuroimmune response: Stimulus specific changes elicited by bacterial and viral mimetics. J Physiol 2006; 571(Pt 3): 695-701.
[http://dx.doi.org/10.1113/jphysiol.2005.102939] [PMID: 16423854]
[32]
Bilbo SD, Schwarz JM. The immune system and developmental programming of brain and behavior. Front Neuroendocrinol 2012; 33(3): 267-86.
[http://dx.doi.org/10.1016/j.yfrne.2012.08.006] [PMID: 22982535]
[33]
Goshen I, Kreisel T, Ben-Menachem-Zidon O, et al. Brain interleukin-1 mediates chronic stress-induced depression in mice via adrenocortical activation and hippocampal neurogenesis suppression. Mol Psychiatry 2008; 13(7): 717-28.
[http://dx.doi.org/10.1038/sj.mp.4002055] [PMID: 17700577]
[34]
Bilbo SD, Yirmiya R, Amat J, Paul ED, Watkins LR, Maier SF. Bacterial infection early in life protects against stressor-induced depressive-like symptoms in adult rats. Psychoneuroendocrinology 2008; 33(3): 261-9.
[http://dx.doi.org/10.1016/j.psyneuen.2007.11.008] [PMID: 18164556]
[35]
Doosti MH, Bakhtiari A, Zare P, et al. Impacts of early intervention with fluoxetine following early neonatal immune activation on depression-like behaviors and body weight in mice. Prog Neuropsychopharmacol Biol Psychiatry 2013; 43: 55-65.
[http://dx.doi.org/10.1016/j.pnpbp.2012.12.003] [PMID: 23270703]
[36]
Wang KC, Fan LW, Kaizaki A, Pang Y, Cai Z, Tien LT. Neonatal lipopolysaccharide exposure induces long-lasting learning impairment, less anxiety-like response and hippocampal injury in adult rats. Neuroscience 2013; 234: 146-57.
[http://dx.doi.org/10.1016/j.neuroscience.2012.12.049] [PMID: 23298854]
[37]
Musaelyan K, Egeland M, Fernandes C, et al. Modulation of Adult Hippocampal Neurogenesis by early-life environmental challenges triggering immune activation 2014; 2014 194396.
[http://dx.doi.org/10.1155/2014/194396]
[38]
Smith PL, Hagberg H, Naylor AS, Mallard C. Neonatal peripheral immune challenge activates microglia and inhibits neurogenesis in the developing murine hippocampus. Dev Neurosci 2014; 36(2): 119-31.
[http://dx.doi.org/10.1159/000359950] [PMID: 24642725]
[39]
Bondar NP, Merkulova TI. Brain-derived neurotrophic factor and early-life stress: Multifaceted interplay. J Biosci 2016; 41(4): 751-8.
[http://dx.doi.org/10.1007/s12038-016-9648-3] [PMID: 27966494]
[40]
Lee CH, Giuliani F. The role of inflammation in depression and fatigue. Front Immunol 2019; 10: 1696.
[41]
Han Y, Sun CY, Meng SQ, et al. Systemic immunization with altered myelin basic protein peptide produces sustained antidepressant-like effects. Mol Psychiatry 2019. [Epub ahead of print]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 16
ISSUE: 4
Year: 2019
Page: [358 - 364]
Pages: 7
DOI: 10.2174/1567202616666191007125502
Price: $58

Article Metrics

PDF: 13
HTML: 2

Special-new-year-discount