Depressive-like parameters in sepsis survivor rats.
The inflammatory and immune responses evoked in sepsis may create not only an acute brain dysfunction, which occurs in the majority of septic patients, but also long-term deficits such as memory impairment. In this context, we evaluated depressive-like parameters in sepsis survivor rats. For this purpose, male Wistar rats, weighing 300-350 g, underwent cecal ligation and perforation (CLP) (sepsis group) followed by "basic support", or were sham-operated (control group). After 3 days of the sepsis procedure, the animals were treated with imipramine at 10 mg/kg or saline during 14 days (days 3-17). The consumption of sweet food was measured for 7 days (days 10-17) and the body weight was measured before CLP, 10, and 17 days after CLP. Seventeen days after sepsis (immediately after sweet food consumption measurement), the animals were anesthetized and blood was withdrawn for the analyses of corticosterone and adrenocorticotropic hormone (ACTH) levels, and immediately killed by decapitation. The adrenal gland and hippocampus were immediately isolated and weighed, and the hippocampus was utilized for determining brain-derived neurotrophic factor (BDNF) levels. It was observed that animals subjected to CLP presented decreased sucrose intake. Septic rats did not increase body weight and presented an increase in the weight of adrenal gland. Both corticosterone and ACTH levels were increased, while hippocampus weight and BDNF levels in the hippocampus decreased. The treatment with imipramine reversed all the parameters described above. Our results supported the hypothesis that rats that survive sepsis show depressive-like behavior, alterations in the hypothalamus-pituitary-adrenal axis, and decreased BDNF levels in the hippocampus.
Comim
Clarissa M
CM
Instituto Nacional de Ciência e Tecnologia Translacional em Medicina, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
Cassol
Omar J
OJ
Constantino
Leandra C
LC
Petronilho
Fabrícia
F
Constantino
Larissa S
LS
Stertz
Laura
L
Kapczinski
Flávio
F
Barichello
Tatiana
T
Quevedo
João
J
Dal-Pizzol
Felipe
F
D000311:Adrenal Glands / Q000187:drug effects; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D003863:Depression / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology; D004195:Disease Models, Animal; D005518:Food Preferences / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007099:Imipramine / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000150:complications*
D000929:Antidepressive Agents, Tricyclic; D019208:Brain-Derived Neurotrophic Factor; D000324:Adrenocorticotropic Hormone; D007099:Imipramine; D003345:Corticosterone
Neuroscience. 2006 May 12;139(2):779-89
16457953
Clin Invest Med. 1990 Dec;13(6):297-304
2078909
Curr Opin Pharmacol. 2007 Feb;7(1):18-21
17049922
Nat Clin Pract Endocrinol Metab. 2008 Sep;4(9):496-505
18695699
Prog Neurobiol. 2005 Jun;76(2):99-125
16099088
Pharmacol Biochem Behav. 2006 Dec;85(4):842-9
17204313
Neurochem Int. 2003 Jan;42(2):107-14
12421590
Mitochondrion. 2008 Sep;8(4):313-8
18657632
Neuroendocrinology. 2001 Sep;74(3):148-59
11528216
Psychopharmacology (Berl). 2006 Jul;186(4):601-11
16758243
Brain Res Brain Res Rev. 2004 May;45(2):104-14
15145621
Behav Pharmacol. 2005 May;16(3):171-80
15864072
Front Neuroendocrinol. 2004 Jul;25(2):77-107
15571756
Crit Care Med. 2001 Jul;29(7):1303-10
11445675
Psychopharmacology (Berl). 1998 Apr;136(3):272-83
9566813
Crit Rev Neurobiol. 1995;9(2-3):189-205
8581983
Nature. 2008 Oct 16;455(7215):894-902
18923511
Intensive Care Med. 2003 Oct;29(10):1782-9
12783160
Brain Behav Immun. 2006 Jan;20(1):1-8
16140497
Brain Res. 2001 Apr 27;899(1-2):227-39
11311884
Crit Care Med. 2007 Sep;35(9 Suppl):S596-601
17713415
Crit Care Med. 2003 Apr;31(4):1226-34
12682497
Psychosom Med. 2005 May-Jun;67 Suppl 1:S26-8
15953796
Biol Psychiatry. 2006 Jun 15;59(12):1116-27
16631126
Neurochem Res. 2008 Nov;33(11):2171-7
18461451
J Neurosci. 1997 Apr 1;17(7):2295-313
9065491
Biol Psychiatry. 2002 Sep 15;52(6):503-28
12361666
Curr Neurovasc Res. 2008 Nov;5(4):207-13
18991655
Immunol Today. 2000 Jun;21(6):281-9
10825740
Neurosci Biobehav Rev. 1981 Summer;5(2):231-46
7022272
Physiol Behav. 1988;44(4-5):483-90
2853383
Drug News Perspect. 2006 Dec;19(10):603-8
17299602
Psychiatry Res. 2002 Mar 15;109(2):143-8
11927139
Neurochem Int. 1997 Apr-May;30(4-5):427-31
9106257
Brain Res. 2008 Feb 27;1196:41-52
18234161
Intensive Care Med. 2007 Dec;33(12):2165-7
17668182
Neuropsychopharmacology. 2004 Apr;29(4):795-8
14735133
Arch Gen Psychiatry. 1994 Jan;51(1):8-19
8279933
Curr Top Microbiol Immunol. 1996;216:39-81
8791735
Neuroimmunomodulation. 1994 Jul-Aug;1(4):251-8
7489340
Anaesthesia. 2001 Jan;56(1):9-14
11167429
Ann N Y Acad Sci. 2000;917:876-93
11268419
Mol Cell Neurosci. 2004 Nov;27(3):280-95
15519243
Neuroscience. 2002;112(2):309-18
12044449
Prog Neuropsychopharmacol Biol Psychiatry. 2009 Apr 30;33(3):450-5
19439250
J Neuroimmunol. 2006 Mar;172(1-2):38-58
16375977
Physiol Rev. 2007 Jul;87(3):873-904
17615391
Exp Neurol. 2007 Apr;204(2):733-40
17306796
Vitam Horm. 1983;40:145-74
6673332
Arch Gen Psychiatry. 1997 Jul;54(7):597-606
9236543
Annu Rev Neurosci. 1996;19:289-317
8833445
Crit Care Med. 1990 Aug;18(8):801-6
2379391
Ann N Y Acad Sci. 2002 Jun;966:20-7
12114255
Intensive Care Med. 2008 Sep;34(9):1724-31
18542919
Psychopharmacology (Berl). 1987;93(3):358-64
3124165
Neurosci Biobehav Rev. 2005 Feb;29(1):3-38
15652252
J Affect Disord. 2007 Aug;101(1-3):239-44
17173978