PMID- 32720073
OWN - NLM
STAT- MEDLINE
DCOM- 20210609
LR  - 20210609
IS  - 1559-1182 (Electronic)
IS  - 0893-7648 (Linking)
VI  - 57
IP  - 10
DP  - 2020 Oct
TI  - Maternal Immune Activation Causes Schizophrenia-like Behaviors in the Offspring 
      through Activation of Immune-Inflammatory, Oxidative and Apoptotic Pathways, and 
      Lowered Antioxidant Defenses and Neuroprotection.
PG  - 4345-4361
LID - 10.1007/s12035-020-02028-8 [doi]
AB  - Schizophrenia is a complex neuropsychiatric disorder, influenced by a combined 
      action of genes and environmental factors. The neurodevelopmental origin is one 
      of the most widely recognized etiological models of this heterogeneous disorder. 
      Environmental factors, especially infections during gestation, appear to be a 
      major risk determinant of neurodevelopmental basis of schizophrenia. Prenatal 
      infection may cause maternal immune activation (MIA) and enhance risk of 
      schizophrenia in the offspring. However, the precise mechanistic basis through 
      which MIA causes long-lasting schizophrenia-like behavioral deficits in offspring 
      remains inadequately understood. Herein, we aimed to delineate whether prenatal 
      infection-induced MIA causes schizophrenia-like behaviors through its 
      long-lasting effects on immune-inflammatory and apoptotic pathways, oxidative 
      stress toxicity, and antioxidant defenses in the brain of offspring. 
      Sprague-Dawley rats were divided into three groups (n = 15/group) and were 
      injected with poly (I:C), LPS, and saline at gestational day (GD)-12. 
      Except IL-1beta, plasma levels of IL-6, TNF-alpha, and IL-17A assessed after 24 h were 
      significantly elevated in both the poly (I:C)- and LPS-treated pregnant rats, 
      indicating MIA. The rats born to dams treated with poly (I:C) and LPS displayed 
      increased anxiety-like behaviors and significant deficits in social behaviors. 
      Furthermore, the hippocampus of the offspring rats of both the poly (I:C)- and 
      LPS-treated groups showed increased signs of lipid peroxidation, diminished total 
      antioxidant content, and differentially upregulated expression of inflammatory 
      (TNFalpha, IL6, and IL1beta), and apoptotic (Bax, Cas3, and Cas9) genes but decreased 
      expression of neuroprotective (BDNF and Bcl2) genes. The results suggest 
      long-standing effects of prenatal infections on schizophrenia-like behavioral 
      deficits, which are mediated by immune-inflammatory and apoptotic pathways, 
      increased oxidative stress toxicity, and lowered antioxidant and neuroprotective 
      defenses. The findings suggest that prenatal infections may underpin 
      neurodevelopmental aberrations and neuroprogression and subsequently 
      schizophrenia-like symptoms.
FAU - Talukdar, Pinku Mani
AU  - Talukdar PM
AD  - Department of Human Genetics, National Institute of Mental Health and 
      Neurosciences (NIMHANS), Hosur Road, Bangalore, 560029, India.
FAU - Abdul, Fazal
AU  - Abdul F
AD  - Department of Human Genetics, National Institute of Mental Health and 
      Neurosciences (NIMHANS), Hosur Road, Bangalore, 560029, India.
FAU - Maes, Michael
AU  - Maes M
AD  - Department of Psychiatry, Faculty of Medicine, King Chulalongkorn Memorial 
      Hospital, Bangkok, Thailand.
AD  - Department of Psychiatry, Medical University of Plovdiv, Plovdiv, Bulgaria.
AD  - IMPACT Strategic Research Center, Deakin University, Geelong, Australia.
FAU - Binu, V S
AU  - Binu VS
AD  - Department of Biostatistics, National Institute of Mental Health and 
      Neurosciences (NIMHANS), Bengaluru, India.
FAU - Venkatasubramanian, Ganesan
AU  - Venkatasubramanian G
AD  - Department of Psychiatry, National Institute of Mental Health and Neurosciences 
      (NIMHANS), Bengaluru, India.
FAU - Kutty, Bindu M
AU  - Kutty BM
AD  - Department of Neurophysiology, National Institute of Mental Health and 
      Neurosciences (NIMHANS), Bengaluru, India.
FAU - Debnath, Monojit
AU  - Debnath M
AUID- ORCID: 0000-0002-5843-072X
AD  - Department of Human Genetics, National Institute of Mental Health and 
      Neurosciences (NIMHANS), Hosur Road, Bangalore, 560029, India. 
      monozeet@gmail.com.
LA  - eng
GR  - SR/WOS-A/LS-1219/2014(G)/Department of Science and Technology, Government of 
      Kerala/
PT  - Journal Article
DEP - 20200727
PL  - United States
TA  - Mol Neurobiol
JT  - Molecular neurobiology
JID - 8900963
RN  - 0 (Antioxidants)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Thiobarbituric Acid Reactive Substances)
RN  - O84C90HH2L (Poly I-C)
SB  - IM
MH  - Animals
MH  - Antioxidants/*metabolism
MH  - Anxiety/blood/complications/immunology
MH  - *Apoptosis/genetics
MH  - Behavior, Animal
MH  - Brain/pathology
MH  - Female
MH  - Gene Expression Regulation
MH  - Inflammation/blood/*immunology
MH  - Lipopolysaccharides
MH  - *Neuroprotection/genetics
MH  - *Oxidative Stress
MH  - Poly I-C
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/blood/*immunology
MH  - Prepulse Inhibition
MH  - Rats, Sprague-Dawley
MH  - Schizophrenia/blood/complications/*immunology
MH  - *Signal Transduction
MH  - Social Behavior
MH  - Thiobarbituric Acid Reactive Substances/metabolism
MH  - Up-Regulation
OTO - NOTNLM
OT  - Inflammation
OT  - Maternal immune activation
OT  - Neuro-immune
OT  - Neuroprotection
OT  - Oxidative stress
OT  - Schizophrenia-like behaviors
EDAT- 2020/07/29 06:00
MHDA- 2021/06/10 06:00
CRDT- 2020/07/29 06:00
PHST- 2020/05/01 00:00 [received]
PHST- 2020/07/14 00:00 [accepted]
PHST- 2020/07/29 06:00 [pubmed]
PHST- 2021/06/10 06:00 [medline]
PHST- 2020/07/29 06:00 [entrez]
AID - 10.1007/s12035-020-02028-8 [pii]
AID - 10.1007/s12035-020-02028-8 [doi]
PST - ppublish
SO  - Mol Neurobiol. 2020 Oct;57(10):4345-4361. doi: 10.1007/s12035-020-02028-8. Epub 
      2020 Jul 27.