Sex-dependent effects of neonatal inflammation on adult inflammatory markers and behavior.
Inflammatory molecules, such as cyclooxygenase (COX), a prostaglandin synthetic enzyme, have been identified as a marker of depressive symptomology. Previously, we have observed elevated basal COX-2 expression in the hypothalamus of adult male rats treated neonatally with lipopolysaccharide (LPS), which might suggest a phenotype for disrupted hedonic behavior, a symptom of depression. However, COX-2 and its contribution to the expression of anhedonic behavior has not been investigated in these males or in female rats across the estrous cycle, which is the purpose of the current work. Here, we examine the effects of a neonatal LPS challenge or saline on the sucrose preference test as a measure of anhedonia, and hypothalamic COX-2 expression, in adult male and freely cycling female rats. Our data indicate a sex difference in that neonatal LPS at postnatal d 14 causes elevated basal expression of hypothalamic COX-2 in male, but not in female, rats. Additionally, baseline sucrose preference in male and female rats was unaltered as a function of neonatal LPS treatment or estrous cycle stage. In both male and female animals, 50 microg/kg LPS in adulthood caused elevated plasma IL-6 and hypothalamic COX-2 expression in neonatally saline-treated rats but significantly less so in neonatally LPS-treated rats of both sexes; this neonatal programming was not evident for sucrose preference or for total fluid intake (even after much higher doses of LPS). Our data are suggestive of a dissociation between inflammation and anhedonic behavior and a differential effect of neonatal inflammation in males and females.
Kentner
A C
AC
Department of Physiology and Pharmacology, Hotchkiss Brain Institute, 3330 Hospital Drive N.W., Calgary, Alberta, Canada T2N 4N1. ackentne@ucalgary.ca
McLeod
S A
SA
Field
E F
EF
Pittman
Q J
QJ
D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D030762:Estrous Cycle / Q000187:drug effects; D005260:Female; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007249:Inflammation / Q000097:blood / Q000139:chemically induced / Q000378:metabolism*; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D011247:Pregnancy; D051381:Rats; D012737:Sex Factors
D015850:Interleukin-6; D008070:Lipopolysaccharides; D051546:Cyclooxygenase 2
Pharmacol Biochem Behav. 2001 Jul-Aug;69(3-4):659-63
11509229
J Neurosci. 2008 Sep 3;28(36):9055-65
18768700
Psychopharmacology (Berl). 1989;98(3):408-11
2501818
Neuropsychopharmacology. 2006 Sep;31(9):1910-8
16395304
Brain Res Mol Brain Res. 1998 May;56(1-2):45-56
9602052
Epilepsia. 2004 Nov;45(11):1317-29
15509232
Psychoneuroendocrinology. 1981;6(1):81-90
7195598
Endocrinology. 2005 Apr;146(4):1650-73
15618360
Neurosci Biobehav Rev. 2005;29(4-5):761-70
15878621
Cell Biol Int. 1996 Oct;20(10):687-92
8969462
Mol Psychiatry. 2002;7(8):845-50
12232777
Psychoneuroendocrinology. 2009 Nov;34(10):1515-25
19524372
Pharmacogenomics J. 2006 Nov-Dec;6(6):381-7
16568149
FASEB J. 2005 Sep;19(11):1519-21
15972802
Am J Physiol Regul Integr Comp Physiol. 2006 Nov;291(5):R1215-21
16809485
Eur J Neurosci. 2008 Feb;27(3):644-53
18279317
Psychopharmacology (Berl). 2003 Dec;170(4):399-408
12955300
Am J Physiol. 1990 Mar;258(3 Pt 2):R798-803
2316725
Physiol Behav. 2009 May 25;97(2):270-7
19268677
Brain Behav Immun. 2009 Oct;23(7):977-85
19464359
Eur J Pharmacol. 2009 Jun 10;612(1-3):54-60
19356723
Hum Psychopharmacol. 2008 Mar;23(2):87-94
18172906
Curr Biol. 2008 Feb 12;18(3):195-9
18261909
Brain Behav Immun. 2008 Nov;22(8):1160-72
18562160
Pharmacol Biochem Behav. 2003 Aug;76(1):153-9
13679228
Physiol Behav. 1971 Feb;6(2):115-26
5125467
Neuropsychopharmacology. 2001 May;24(5):531-44
11282253
Depress Anxiety. 2009;26(7):607-11
19496103
Behav Brain Res. 2005 Nov 7;164(2):231-8
16125259
Pain. 2005 Dec 15;119(1-3):133-141
16297551
Psychoneuroendocrinology. 2007 Jun;32(5):516-31
17482371
Brain Res. 1996 Mar 4;711(1-2):163-74
8680860
Behav Brain Res. 2006 Apr 25;169(1):39-47
16413067
Life Sci. 1995;57(11):1011-26
7658909
Prog Brain Res. 2000;122:81-103
10737052
J Neurosci. 2008 Jul 2;28(27):6904-13
18596165
Neuroimmunomodulation. 2001;9(3):163-9
11752890
Endocrinology. 2003 Jun;144(6):2454-60
12746307
Birth Defects Res B Dev Reprod Toxicol. 2007 Apr;80(2):84-97
17342777
Behav Brain Res. 2004 Feb 4;149(1):77-85
14739012
J Neurosci. 1995 Jan;15(1 Pt 1):376-84
7823142
Mol Psychiatry. 2006 Jul;11(7):680-4
16491133
J Neurosci. 2004 May 26;24(21):4928-34
15163684
Brain Behav Immun. 2006 Jul;20(4):325-30
16226008
Behav Neurosci. 2005 Feb;119(1):293-301
15727533
Psychoneuroendocrinology. 2009 Apr;34(3):343-52
18977603
Eur J Neurosci. 2007 May;25(10):3091-8
17561822
Behav Brain Res. 2007 Jun 18;180(2):161-73
17433456
J Steroid Biochem Mol Biol. 2008 Apr;109(3-5):300-6
18430566
Braz J Biol. 2002 Nov;62(4A):609-14
12659010
Stress. 2007 Aug;10(3):283-93
17613942
Neuropsychopharmacology. 2006 Jan;31(1):129-38
15920500
Neurotoxicol Teratol. 2007 Mar-Apr;29(2):255-63
17169529
Trends Pharmacol Sci. 1992 Jan;13(1):24-8
1542935
Am J Physiol Regul Integr Comp Physiol. 2007 Aug;293(2):R581-9
17507437
Psychoneuroendocrinology. 2008 Apr;33(3):261-9
18164556
J Neuroinflammation. 2008 May 13;5:15
18477398
Pharmacol Biochem Behav. 2003 Aug;76(1):9-16
13679212
J Neuroendocrinol. 2009 Aug;21(8):683-9
19500221
Drug Alcohol Depend. 2007 Jul 10;89(2-3):183-9
17240083
Psychopharmacology (Berl). 2005 May;179(2):356-65
15565429
Neurosci Biobehav Rev. 1988 Summer;12(2):123-37
3050629
Proc Soc Exp Biol Med. 1983 Jul;173(3):319-23
6346326
Pharmacol Biochem Behav. 2006 Jul;84(3):429-35
16844207
Am J Physiol Regul Integr Comp Physiol. 2006 Nov;291(5):R1316-26
16809483