title: Effects of acute restraint stress, prolonged captivity stress and transdermal corticosterone application on immunocompetence and plasma levels of corticosterone on the cururu Toad (Rhinella icterica).
abstract: Glucocorticoid steroids modulate immunocompetence in complex ways with both immunoenhancing and immunosuppressive effects in vertebrates exposed to different stressors. Such bimodal effects have been associated with variation in duration and intensity of the stress response. Given that natural populations have been exposed to a multitude of stressors, a better understanding of the functional association between duration and intensity of the stress response, the resulting changes in glucocorticoid plasma levels and their impact on different aspects of immunocompetence emerges as a cornerstone for vertebrate conservation strategies. We investigated the effects of a restraint challenge (with and without movement restriction), long-term captivity, and transdermal corticosterone application on plasma levels of corticosterone (hereinafter referred to as CORT) and different parameters of innate immunocompetence in the male cururu toads (Rhinella icterica). We show that for R. icterica restraint for 24h proved to be a stressful condition, increasing CORT by 3-fold without consistent immunological changes. However, the application of a more intense stressor (restraint with movement restriction), for the same period, potentiated this response resulting in a 9-fold increase in CORT, associated with increase Neutrophil/Lymphocyte ratio (N:L) and a lower bacterial killing ability (BKA). Transdermal application of corticosterone efficiently mimics repeated acute stress response events, without changing the immune parameters even after 13 days of treatment. Interestingly, long-term captivity did not mitigate the stress response, since the toads maintained 3-fold increased CORT even after 3 months under these conditions. Moreover, long-term captivity in the same condition increased total leukocyte count (TLC) and generated an even greater decrease in BKA, suggesting that consequences of the stress response can be aggravated by time in captivity.
authors.affiliation: Departamento de Fisiologia, Instituto de Biociências, Universidade de São Paulo, Rua do Matão, trav. 14, 101, 05508-900, São Paulo, SP, Brazil.
authors.forename: Vania Regina
authors.initials: VR
authors.lastname: de Assis
authors.affiliation: Departamento de Fisiologia, Instituto de Biociências, Universidade de São Paulo, Rua do Matão, trav. 14, 101, 05508-900, São Paulo, SP, Brazil.
authors.forename: Stefanny Christie Monteiro
authors.initials: SC
authors.lastname: Titon
authors.affiliation: Departamento de Fisiologia, Instituto de Biociências, Universidade de São Paulo, Rua do Matão, trav. 14, 101, 05508-900, São Paulo, SP, Brazil.
authors.forename: Adriana Maria Giorgi
authors.initials: AM
authors.lastname: Barsotti
authors.affiliation: Departamento de Fisiologia, Instituto de Biociências, Universidade de São Paulo, Rua do Matão, trav. 14, 101, 05508-900, São Paulo, SP, Brazil.
authors.forename: Braz
authors.initials: B
authors.lastname: Titon
authors.affiliation: Departamento de Fisiologia, Instituto de Biociências, Universidade de São Paulo, Rua do Matão, trav. 14, 101, 05508-900, São Paulo, SP, Brazil.
authors.forename: Fernando Ribeiro
authors.initials: FR
authors.lastname: Gomes
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D002024:Bufo marinus / Q000378:metabolism; D003345:Corticosterone / Q000008:administration & dosage* / Q000097:blood; D007113:Immunity, Innate; D007121:Immunocompetence; D007124:Immunoenzyme Techniques; D007958:Leukocyte Count; D008214:Lymphocytes / Q000166:cytology; D008297:Male; D009504:Neutrophils / Q000166:cytology; D012149:Restraint, Physical
chemical_list: D003345:Corticosterone
references.citation: Conserv Biol. 2012 Oct;26(5):923-31
references.pmid: 22891816
references.citation: Annu Rev Pharmacol Toxicol. 1998;38:1-20
references.pmid: 9597146
references.citation: Horm Behav. 2012 Jul;62(2):146-53
references.pmid: 22713726
references.citation: Am Nat. 2001 Apr;157(4):408-20
references.pmid: 18707250
references.citation: Gen Comp Endocrinol. 2011 Sep 1;173(2):371-7
references.pmid: 21756910
references.citation: Gen Comp Endocrinol. 2013 Sep 15;191:177-89
references.pmid: 23816765
references.citation: Philos Trans R Soc Lond B Biol Sci. 1996 Nov 29;351(1347):1539-57
references.pmid: 8962441
references.citation: Gen Comp Endocrinol. 2003 Dec;134(3):316-29
references.pmid: 14636639
references.citation: Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):9031-6
references.pmid: 9671799
references.citation: J Pineal Res. 2005 Apr;38(3):182-8
references.pmid: 15725340
references.citation: Physiol Biochem Zool. 2008 May-Jun;81(3):383-7
references.pmid: 18279038
references.citation: Dialogues Clin Neurosci. 2006;8(4):417-32
references.pmid: 17290800
references.citation: Horm Behav. 1996 Jun;30(2):153-61
references.pmid: 8797024
references.citation: Proc Soc Exp Biol Med. 1958 Mar;97(3):502-5
references.pmid: 13518317
references.citation: Evolution. 1987 Sep;41(5):1116-1120
references.pmid: 28563412
references.citation: Proc Natl Acad Sci U S A. 2007 Nov 6;104(45):17698-700
references.pmid: 17951431
references.citation: Immunology. 1975 Apr;28(4):669-80
references.pmid: 1080130
references.citation: J Therm Biol. 2014 Apr;41:72-6
references.pmid: 24679975
references.citation: Neuroimmunomodulation. 2009;16(5):300-17
references.pmid: 19571591
references.citation: Endocrinology. 1994 Dec;135(6):2351-7
references.pmid: 7988417
references.citation: J Exp Biol. 2006 Jan;209(Pt 2):284-91
references.pmid: 16391350
references.citation: J Neuroendocrinol. 2002 Sep;14(9):691-5
references.pmid: 12213130
references.citation: Environ Toxicol Chem. 2003 Jan;22(1):101-10
references.pmid: 12503752
references.citation: Gen Comp Endocrinol. 2011 Nov 1;174(2):107-15
references.pmid: 21872597
references.citation: Comp Biochem Physiol A Mol Integr Physiol. 2003 Mar;134(3):497-503
references.pmid: 12600658
references.citation: Brain Behav Immun. 2002 Dec;16(6):785-98
references.pmid: 12480507
references.citation: Trends Pharmacol Sci. 1998 Aug;19(8):317-21
references.pmid: 9745359
references.citation: Gen Comp Endocrinol. 2010 Dec 1;169(3):269-75
references.pmid: 20850442
references.citation: Dev Comp Immunol. 1999 Sep;23(6):459-72
references.pmid: 10512457
references.citation: Comp Biochem Physiol A Mol Integr Physiol. 2012 Feb;161(2):153-8
references.pmid: 22047668
references.citation: Comp Biochem Physiol A Mol Integr Physiol. 2012 Jul;162(3):171-6
references.pmid: 22387450
references.citation: J Wildl Dis. 1999 Jan;35(1):49-57
references.pmid: 10073345
references.citation: Gen Comp Endocrinol. 2014 Aug 1;204:135-40
references.pmid: 24852352
references.citation: Brain Res Bull. 2009 Dec 16;80(6):331-6
references.pmid: 19772903
references.citation: J Clin Invest. 1968 Feb;47(2):249-60
references.pmid: 5638121
references.citation: Am J Physiol Regul Integr Comp Physiol. 2005 Jun;288(6):R1628-36
references.pmid: 15886358
references.citation: Gen Comp Endocrinol. 2011 Sep 1;173(2):295-302
references.pmid: 21703273
references.citation: Endocr Rev. 2000 Feb;21(1):55-89
references.pmid: 10696570
references.citation: Mol Phylogenet Evol. 2010 Nov;57(2):787-97
references.pmid: 20813190
references.citation: Comp Biochem Physiol A Mol Integr Physiol. 2005 Jan;140(1):73-9
references.pmid: 15664315
references.citation: Gen Comp Endocrinol. 2006 Sep 1;148(2):163-71
references.pmid: 16581070
references.citation: Comp Biochem Physiol A Mol Integr Physiol. 2010 May;156(1):129-35
references.pmid: 20096361
references.citation: Conserv Physiol. 2013 May 24;1(1):cot011
references.pmid: 27293595
references.citation: J Immunol. 1995 Aug 15;155(4):1893-902
references.pmid: 7636240
references.citation: Horm Behav. 1993 Mar;27(1):29-37
references.pmid: 8440515
references.citation: Gen Comp Endocrinol. 2009 Sep 1;163(1-2):70-6
references.pmid: 19318107
references.citation: Microb Pathog. 1999 Feb;26(2):85-91
references.pmid: 10090855
references.citation: Nature. 2014 Jul 10;511(7508):224-7
references.pmid: 25008531
references.citation: Horm Behav. 2003 Jan;43(1):2-15
references.pmid: 12614627
references.citation: Am J Physiol. 1993 Dec;265(6 Pt 1):E825-30
references.pmid: 8279536
references.citation: Gen Comp Endocrinol. 1973 Aug;21(1):9-15
references.pmid: 4541989
references.citation: PLoS One. 2014 Jun 17;9(6):e99734
references.pmid: 24936876
references.citation: Psychoneuroendocrinology. 2006 Jul;31(6):781-5
references.pmid: 16621323
references.citation: J Exp Zool A Ecol Genet Physiol. 2012 Dec;317(8):499-510
references.pmid: 22791614
references.citation: J Immunol. 1996 Aug 15;157(4):1638-44
references.pmid: 8759750
references.citation: J Immunol. 1972 Mar;108(3):841-4
references.pmid: 4551854