Neonatal behavioral changes in rats with gestational exposure to lipopolysaccharide: a prenatal infection model for developmental neuropsychiatric disorders.
Exposure to prenatal infections has been widely associated with the increased risk for neuropsychiatric disorders of developmental origin such as schizophrenia and autism. Although several behavioral and cognitive deficits have been detected during adulthood in rodent models of prenatal infections, early behavioral changes have not been well characterized. In a prenatal lipopolysaccharide (LPS) model, we have previously observed significant alterations in the neuronal cytoarchitecture during early postnatal life. In the present study, we aimed to investigate the potential effects of prenatal immune activation on early neurophenotypic presentations using a set of behavioral test battery. Female Sprague-Dawley rats were administered with 100 μg/kg LPS (intraperitoneally) at gestational days 15 and 16. During the first postnatal week, we found no significant effect on maternal behavior or mother-pup interaction by this treatment. Also, no major changes in physical developmental milestones of pups were noted from postnatal (P) days P6 to P16. Importantly, prenatal LPS-exposed pups had a significant decrease in the number and duration of ultrasonic vocalization calls at P3 and P5. Prenatal LPS treatment also led to impairments in nest-seeking behavior and odor-stroke associative learning in neonatal rats at P8 and P9. At the molecular level, we detected significant decrease in the expression of cortical 5HT1A and 5HT1B messenger RNA at P3. These data suggest that prenatal exposure to an immune activator can significantly impair the social/communicative behavior in the neonate offspring, which may be relevant to childhood and premorbid abnormalities reported in autism and schizophrenia subjects.
Baharnoori
Moogeh
M
Douglas Mental Health University Institute, Department of Psychiatry, McGill University, 6875 LaSalle Boulevard, Montreal, Quebec, Canada.
Bhardwaj
Sanjeev K
SK
Srivastava
Lalit K
LK
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D015415:Biomarkers; D004195:Disease Models, Animal; D005260:Female; D007239:Infections / Q000139:chemically induced / Q000235:genetics / Q000523:psychology*; D008070:Lipopolysaccharides / Q000009:adverse effects; D001523:Mental Disorders / Q000209:etiology* / Q000235:genetics / Q000523:psychology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000139:chemically induced / Q000235:genetics / Q000523:psychology*; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000235:genetics / Q000523:psychology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D015415:Biomarkers; D008070:Lipopolysaccharides; D012333:RNA, Messenger
Neuropsychopharmacology. 1996 Mar;14(3 Suppl):1S-11S
8866738
Br J Psychiatry. 2004 Mar;184:231-9
14990521
Behav Brain Res. 2009 Jan 30;197(1):210-8
18793679
Child Dev. 1987 Dec;58(6):1431-47
3691193
Ann N Y Acad Sci. 2003 Dec;1008:308-13
14998903
Dev Psychobiol. 2003 Mar;42(2):206-22
12555284
Prog Neuropsychopharmacol Biol Psychiatry. 1991;15(6):745-57
1684873
Biol Psychiatry. 2010 May 15;67(10):965-73
20079486
Anim Behav. 1965 Apr-Jul;13(2):234-41
5835840
Behav Brain Res. 2001 Nov 1;125(1-2):49-56
11682093
Neuropsychopharmacology. 2003 Oct;28(10):1778-89
12865897
Arch Gen Psychiatry. 2008 Jan;65(1):28-37
18180426
Schizophr Bull. 2005 Jul;31(3):650-71
16006593
Dev Psychobiol. 2006 Jan;48(1):71-8
16381030
Neurosci Biobehav Rev. 2005;29(6):913-47
15964075
Brain Pathol. 2007 Oct;17(4):434-47
17919129
Horm Behav. 2007 Jan;51(1):77-88
17034794
Int J Neuropsychopharmacol. 2009 May;12(4):513-24
18752727
Eur Arch Psychiatry Clin Neurosci. 2000;250(6):311-9
11153966
Behav Brain Res. 2008 Mar 5;187(2):371-8
18005969
Schizophr Bull. 2009 May;35(3):528-48
19223657
Behav Brain Res. 2007 Sep 4;182(2):180-92
17379325
J Neuropsychiatry Clin Neurosci. 1997 Winter;9(1):1-17
9017523
Brain. 2003 Nov;126(Pt 11):2455-62
12876151
Schizophr Bull. 2006 Apr;32(2):200-2
16469941
Behav Neurosci. 2005 Aug;119(4):1111-7
16187838
Am J Obstet Gynecol. 2005 Mar;192(3):727-33
15746664
Behav Brain Res. 2007 Aug 6;181(2):270-7
17553574
J Psychiatr Res. 2004 May-Jun;38(3):335-45
15003440
Toxicol Lett. 2010 Feb 1;192(2):245-51
19896524
Cereb Cortex. 2005 Dec;15(12):2013-20
15788701
Schizophr Bull. 2008 Nov;34(6):1054-63
18682377
Proc Natl Acad Sci U S A. 2005 Jul 5;102(27):9643-8
15983371
Neuropharmacology. 2005 May;48(6):903-17
15829260
BMC Bioinformatics. 2006 Feb 22;7:85
16504059
Arch Gen Psychiatry. 2008 Feb;65(2):146-52
18250252
Biol Psychiatry. 2001 Mar 15;49(6):473-86
11257233
Schizophr Bull. 1994;20(3):441-51
7526446
J Neurosci. 2003 Jan 1;23(1):297-302
12514227
Proc Natl Acad Sci U S A. 2008 Feb 5;105(5):1710-5
18227507
Neurotoxicol Teratol. 1995 May-Jun;17(3):253-64
7623735
Dev Psychobiol. 2006 Mar;48(2):162-8
16489598
Early Hum Dev. 1991 Jul;26(1):61-7
1914989
Behav Brain Res. 2009 Dec 7;204(2):313-21
19136031
Brain Behav Immun. 2010 Aug;24(6):881-97
20230889
Curr Protoc Neurosci. 2002 Feb;Chapter 8:Unit 8.14
18428567
J Neurosci. 1998 Dec 1;18(23):10171-9
9822770
Prog Brain Res. 2008;172:117-40
18772030
J Autism Dev Disord. 2003 Aug;33(4):455-9
12959425
J Neurosci. 2004 Feb 4;24(5):1182-9
14762136
Schizophr Bull. 2000;26(2):395-410
10885639
Am J Psychiatry. 2006 May;163(5):790-9
16648318
Curr Neuropharmacol. 2009 Jun;7(2):150-7
19949574
Physiol Behav. 1994 Jun;55(6):993-6
8047590
Schizophr Bull. 2009 Sep;35(5):959-72
18408229
Behav Brain Res. 2007 Feb 12;177(1):142-9
17141885
Brain Res Bull. 1994;35(5-6):467-72
7859104
J Autism Child Schizophr. 1977 Mar;7(1):69-81
576606
Schizophr Res. 2008 Feb;99(1-3):56-70
18248790
Physiol Behav. 2001 Mar;72(4):473-9
11282130
Pediatrics. 2007 Nov;120(5):1183-215
17967920
Dev Psychobiol. 1999 Apr;34(3):205-15
10204096
Lancet. 2009 Nov 7;374(9701):1627-38
19819542
Anim Behav. 1975 Nov;23(4):896-920
1200422
Schizophr Res. 1995 Aug 1;16(2):111-20
7577764
Biol Psychiatry. 2006 Jun 15;59(12):1227-35
16457784
Dev Psychobiol. 2003 Sep;43(2):90-101
12918088
Schizophr Res. 2003 May 1;61(1):19-30
12648732
Trends Neurosci. 2002 Oct;25(10):518-24
12220880
Psychol Med. 2009 Sep;39(9):1457-67
19215630
Biol Psychiatry. 2005 Apr 15;57(8):823-31
15820702
Ann N Y Acad Sci. 2003 Dec;1008:238-47
14998888
Neurosci Biobehav Rev. 2009 Apr;33(4):508-15
18771687
Behav Brain Res. 2005 Nov 7;164(2):214-21
16105697
Behav Neurosci. 2004 Jun;118(3):590-6
15174937
Physiol Behav. 1996 Sep;60(3):1013-8
8873284
Arch Gen Psychiatry. 2004 Aug;61(8):774-80
15289276
Biol Psychiatry. 2006 Mar 15;59(6):546-54
16256957
J Neurosci. 2010 Jan 13;30(2):703-13
20071535
Neuropsychopharmacology. 2007 Aug;32(8):1791-804
17180123
Behav Neurosci. 1998 Dec;112(6):1430-7
9926825
Schizophr Bull. 2007 May;33(3):761-71
17412711
Am J Psychiatry. 1993 Nov;150(11):1654-60
8214173
Cerebellum. 2008;7(3):279-94
18418686
Biol Psychiatry. 2009 Jun 15;65(12):1040-7
19195645
Dev Psychobiol. 2003 Mar;42(2):194-205
12555283
Behav Neural Biol. 1993 Sep;60(2):152-62
7906939
Neuron. 2009 Oct 15;64(1):61-78
19840550
Neuropsychopharmacology. 2005 Jan;30(1):80-9
15238991
Schizophr Res. 2009 Jan;107(1):99-109
19004618
Neurosci Biobehav Rev. 2003 Jan-Mar;27(1-2):91-101
12732226
Schizophr Bull. 2009 May;35(3):631-7
18832344
Neurosci Biobehav Rev. 1998;23(2):215-27
9884114
Am J Psychiatry. 2010 Mar;167(3):261-80
20123911
Psychopharmacology (Berl). 2008 Jul;198(4):529-37
18452035
Curr Opin Neurobiol. 2007 Feb;17(1):103-11
17275283
Behav Neurosci. 1999 Jun;113(3):587-601
10443785
Schizophr Bull. 2003;29(4):653-69
14989405
Brain Behav Immun. 2008 May;22(4):469-86
18023140
Hippocampus. 2008;18(6):602-9
18306297
Schizophr Res. 2006 May;84(1):67-76
16677803
Physiol Behav. 1996 Jul;60(1):299-304
8804680
Stress. 2009 May;12(3):250-8
18951246
Synapse. 2005 Aug;57(2):91-9
15906383
Neuroinformatics. 2007 Spring;5(1):79-94
17426354
Int J Dev Neurosci. 2009 Apr;27(2):149-55
19103275