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Polyinosinic:polycytidylic acid 

Inducer Abbreviation: PolyI:C
Model Subtype: Biological
Model Species:Mus musculus
External Link:    
Statistics Box:
No of Reports: 13
No of Models: 26




Model Summary

A model to experimentally show that prenatal immune activation is an environmental risk factor for adult ventricular enlargement

Human Clinical Evidence NA NA


Strong epidemiological evidence suggests that maternal infection during prenatal life may contribute to an increased risk of schizophrenia or autism in offspring

Exposure

Prenatal exposure from mother

Mode of Action

Maternal immune activation

Usage

Immunostimulant

References

Type
Title
Author, Year
Primary
Maternal influenza infection causes marked behavioral and pharmacological changes in the offspring.
Additional
Antipurinergic therapy corrects the autism-like features in the poly(IC) mouse model.
Additional
Modeling an autism risk factor in mice leads to permanent immune dysregulation.
Additional
Prenatal immune challenge is an environmental risk factor for brain and behavior change relevant to schizophrenia: evidence from MRI in a mouse model.
Additional
Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders.
Additional
Maternal immune activation and strain specific interactions in the development of autism-like behaviors in mice.
Additional
Maternal immune activation yields offspring displaying mouse versions of the three core symptoms of autism.
Additional
Maternal immune activation leads to selective functional deficits in offspring parvalbumin interneurons.
Additional
Maternal immune activation alters fetal brain development through interleukin-6.
Additional
Gestational exposure to a viral mimetic poly(i:C) results in long-lasting changes in mitochondrial function by leucocytes in the adult offspring.
Additional
Effects of maternal immune activation on gene expression patterns in the fetal brain.
Additional
Voxel-based analysis of postnatal white matter microstructure in mice exposed to immune challenge in early or late pregnancy.
Additional
The maternal interleukin-17a pathway in mice promotes autism-like phenotypes in offspring.

POLYIC_3_IN_B

Construct Definition: Administration of PolyI:C on E9.5
Administration Dose: 20 mg/g
Administration Route: Intraperitoneal (i.p.)
Administration Age: E9.5
Strain of Origin: BALB/c
Model Source: Simonson Laboratories

POLYIC_6_IN_B

Construct Definition: Administration of PolyI:C on E12.5
Administration Dose: 20 mg/kg
Administration Route: Intraperitoneal (i.p.)
Administration Age: E12.5
Strain of Origin: C57BL/6J
Model Source: Jackson Laboratory

POLYIC_1_IN_B

Construct Definition: Administration of PolyI:C on E9 and E17 in 5 ml/kg
Administration Dose: 5 mg/kg
Administration Route: Intravenous (i.v.)
Administration Age: E9, E17
Strain of Origin: C57BL/6N
Model Source: Univ. of Hong Kong, LAU

POLYIC_2_IN_B

Construct Definition: Administration of PolyI:C on E17 in 5 ml/kg
Administration Dose: 5 mg/kg
Administration Route: Intravenous (i.v.)
Administration Age: E17
Strain of Origin: C57BL/6N
Model Source: Univ. of Hong Kong, LAU

POLYIC_4_IN_B

Construct Definition: Administration of PolyI:C on E9 in 5 ml/kg
Administration Dose: 5 mg/kg
Administration Route: Intravenous (i.v.)
Administration Age: E9
Strain of Origin: C57BL/6N
Model Source: Univ. of Hong Kong, LAU

POLYIC_5_IN_B

Construct Definition: Administration of PolyI:C on E10.5, E12.5, and E14.5
Administration Dose: 5 mg/kg
Administration Route: Intraperitoneal (i.p.)
Administration Age: E10.5, E12.5, E14.5
Strain of Origin: C57BL/6J
Model Source: Jackson Laboratory

POLYIC_7_IN_B

Construct Definition: Administration of PolyI:C on E12.5
Administration Dose: 20 mg/kg
Administration Route: Intraperitoneal (i.p.)
Administration Age: E12.5
Strain of Origin: C57BL/6N
Model Source: Charles River

POLYIC_7_IN_B_BM

Construct Definition: Administration of PolyI:C on E12.5 followed by radiation and injection of bone marrow cells from polyI:C offspring
Administration Dose: 20 mg/kg
Administration Route: Intraperitoneal (i.p.)
Administration Age: E12.5
Strain of Origin: C57BL/6N
Model Source: Charles River

POLYIC_7_IN_B_BM_S

Construct Definition: Administration of PolyI:C on E12.5 followed by radiation and injection of bone marrow cells from saline offspring
Administration Dose: 20 mg/kg
Administration Route: Intraperitoneal (i.p.)
Administration Age: E12.5
Strain of Origin: C57BL/6N
Model Source: Charles River

POLYIC_8_IN_B

Construct Definition: Administration of PolyI:C on E12.5
Administration Dose: 20 mg/kg
Administration Route: Intraperitoneal (i.p.)
Administration Age: E12.5
Strain of Origin: BTBR
Model Source: Jackson Laboratory

POLYIC_10_IN_B

Construct Definition: Administration of PolyI:C on E12.5 (3 mg/kg) and E17.5 (0.125 mg/kg)
Administration Dose: 3 mg/kg; 0.125 mg/kg
Administration Route: Intraperitoneal (i.p.)
Administration Age: E12.5, E17.5
Strain of Origin: C57BL/6J
Model Source: Jackson Laboratory

POLYIC_9_IN_B

Construct Definition: Administration of PolyI:C on E12.5
Administration Dose: 2 mg/kg
Administration Route: Intraperitoneal (i.p.)
Administration Age: E12.5
Strain of Origin: C57BL/6J
Model Source: Jackson Laboratory

POLYIC_11_IN_B

Construct Definition: Administration of PolyI:C on E12.5, the authors note that C57BL/6 mice used were of a stable immunological phenotype as they used these mice to study cytokine levels, therefore these are probably a substrain sold by Taconic. Note that behavioral and anatomical testing is conducted in the offspring but the sera tested are of the pregnant dams
Administration Dose: 20 mg/kg
Administration Route: Intraperitoneal (i.p.)
Administration Age: E12.5
Strain of Origin: C57BL/6J
Model Source: Taconic, USA

POLYIC_6_IN_B_IL6_KO_rIL17a

Construct Definition: Administration of PolyI:C on E12.5 in IL6 knockout mice, at E 14.5 uterine horns of pregnant mice were exposed by a caudal ventral midlineincision (<2 cm). Recombinant mouse IL-17a cytokine (R&D) at 0.6 L of 2 ng/L was injected into the third ventricle of each embryo by a pulled micropipette, after injection of all embryos the uterus was replaced in the abdomen. Note that behavioral and anatomical testing is conducted in the offspring but the sera tested are of the pregnant dams
Administration Dose: 20 mg/kg
Administration Route: Intraperitoneal (i.p.)
Administration Age: E12.5
Strain of Origin:
Model Source:

POLYIC_17_IN_B

Construct Definition: Administration of PolyI:C on E9 to pregnant mice
Administration Dose: 1mg/kg
Administration Route: Intravenous (i.v.)
Administration Age: E9
Strain of Origin: C57BL/6
Model Source: Jackson Laboratory

POLYIC_17_IN_B_PV-ChR2

Construct Definition: Administration of PolyI:C on E9 to pregnant mice with the background of parvalbumin-Cre bred to channel rhodopsin2-YFP flox stop reporter line, resulting in channel rhodopsin being expressed in the parvalbumin positive neurons. This line was used to measure the functional GABAergic connectivity between populations of prefrontal parvalbumin expressing interneurons with their post synaptic pyramidal cell targets
Administration Dose: 1mg/kg
Administration Route: Intravenous (i.v.)
Administration Age: E9
Strain of Origin: 129S6/SvEvTac * C57BL/6NCrl*129P2/OlaHsd
Model Source: PMID-26830140

POLYIC_3_IN_B

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
  Sensorimotor gating 1
  Decreased
Description:  Decreased sensorimotor gating demonstrated by significant PPI deficits at prepuless of 75 dB and 80 dB
Exp Paradigm:  Prepulse inhibition (PPI) assay
  Prepulse inhibition
  4-8 weeks
 Not Reported: Circadian sleep/wake cycle ,   Communications ,   Developmental profile ,   Emotion ,   Homeostasis ,   Immune response ,   Learning & memory ,   Maternal behavior ,   Molecular profile ,   Motor phenotype ,   Neuroanatomy / Ultrastructure / Cytoarchitecture ,   Neurophysiology ,   Repetitive behavior ,   Seizure ,   Social behavior ,  

POLYIC_6_IN_B

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
  General locomotor activity: Ambulatory activity 1
  Decreased
Description:  Decrease in total distance traversed, compared to offspring from saline-injected dams
Exp Paradigm:  Open field test
  Open field test
  Adult
  Stereotypy 3
  Increased
Description:  Increased repetitive behavior shown by burying of higher percentage of marbles
Exp Paradigm:  Marble Burying Test
  Marble-burying test
  Unreported
  Sensorimotor gating 1
  Decreased
Description:  Lower prepulse inhibition, compared to offspring from saline-injected dams
Exp Paradigm:  Prepulse inhibition
  Prepulse inhibition
  Adult
  Social approach 1
  Decreased
Description:  No preference for social chamber, which is decreased compared to offspring from saline-injected dams
Exp Paradigm:  Three-chamber social approach test
  Three-chamber social approach test
  Adult
  Social interaction 3
  Decreased
Description:  Decreased social sniffing measured by time spent sniffing novel mouse
Exp Paradigm:  Three chamber social approach
  Three-chamber social approach test: sociability
  10 weeks
  Social approach 3
  Decreased
Description:  Decreased social approach indicated by decreased preference for chamber containing novel mouse
Exp Paradigm:  Three chamber social approach
  Three-chamber social approach test: sociability
  10 weeks
  Social interaction 3
  Decreased
Description:  Decreased sociability determined by difference between time spent in chamber with novel mouse vs. object
Exp Paradigm:  Three chamber social approach
  Three-chamber social approach test: sociability
  10 weeks
  Ultrasonic vocalization 3
  Increased
Description:  Increased number of ultrasonic vocalizations
Exp Paradigm:  Maternal pup sepration ultrasonic vocalization
  Monitoring ultrasonic vocalizations: maternal separation
  P10
  Tissue weight 2
  Decreased
Description:  Decreased placental weight
Exp Paradigm:  Placental weight measurements
  Measurement of placental weight
  Unreported
  Anxiety 1
  Increased
Description:  Increased anxiety measured by decreased number of entries to center of open field, compared to offspring from saline-injected dams
Exp Paradigm:  Open field test
  Open field test
  Adult
  Cued or contextual fear conditioning: Latent inhibition 1
  Decreased
Description:  Lack of significant latent inhibition (measured by increased freezing response), compared to offspring from saline-injected dams
Exp Paradigm:  fear conditioning test: latent inhibition
  Fear conditioning test: latent inhibition
  Adult
  Gene expression 1
  Abnormal
Description:  61 genes show significant (p < 0.01) changes in gene expression, compared to samples from offspring from saline-injected dams
Exp Paradigm:  Gene expression microarray from frontal cortex samples
  Gene expression microarray
  Adult
  Gene expression 2
  Increased
Description:  Increased gene expression of crystallin gene family: cryaa, cryba1 , crybb1, crybb3 and crygb/crygc in embryonic brain 3 h after injection
Exp Paradigm:  Gene Expression
  Gene expression microarray
  E12.5
  Gene expression 2
  Abnormal
Description:  Abnormal transcriptome profile indicated by 294 genes differentially expressed in embryonic brain 3 h after injection
Exp Paradigm:  Gene Expression
  Gene expression microarray
  E12.5
  Protein modification process 4
  Decreased
Description:  Mice born to polyI:C treated dams had 36% reduction in the rate of oxygen uptake, compared to SHAM treated dams. The deficit was located at the level of complex I in the mitochondria
Exp Paradigm:  Specific Proteins Or Protein Modifications Measured
  Mitochondrial oxygen consumption studies: permeablized splenocytes
  12 weeks
Ultrasonic vocalization3
 No Change
 Monitoring ultrasonic vocalizations: maternal separation
 P8
Cytokine levels3
 No Change
 Stimulation of immune cells: splenocytes
 Unreported
Gene expression2
 No Change
 Quantitative PCR (qRT-PCR)
 3.5, 12 months
Self grooming: social context3
 No Change
 Grooming behavior assessments
 Unreported
 Not Reported: Circadian sleep/wake cycle ,   Communications ,   Developmental profile ,   Emotion ,   Homeostasis ,   Immune response ,   Learning & memory ,   Maternal behavior ,   Molecular profile ,   Motor phenotype ,   Neuroanatomy / Ultrastructure / Cytoarchitecture ,   Neurophysiology ,   Repetitive behavior ,   Seizure ,   Sensory ,   Social behavior ,  

POLYIC_1_IN_B

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
  Brain morphology 1
  Abnormal
Description:  Abnormal brain morphology demonstrated by increased CSF volumes in lateral ventricles
Exp Paradigm:  Volumetric analyses of in-vivo Magnetic Resonance Imaging
  Magnetic resonance imaging (MRI)
  12 weeks
  Sensorimotor gating 1
  Abnormal
Description:  Decreased startle reactivity to pulse stimulus indicative of abnormal prepulse inhibition (PPI) of acoustic startle reflex
Exp Paradigm:  PPI (prepulse inhibition) of the acoustic startle reflex
  Prepulse inhibition
  12 weeks
Brain size1
 No Change
 Magnetic resonance imaging (MRI)
 12 weeks
 Not Reported: Circadian sleep/wake cycle ,   Communications ,   Developmental profile ,   Emotion ,   Homeostasis ,   Immune response ,   Learning & memory ,   Maternal behavior ,   Molecular profile ,   Motor phenotype ,   Neurophysiology ,   Repetitive behavior ,   Seizure ,   Social behavior ,  

POLYIC_2_IN_B

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
  Brain morphology 1
  Abnormal
Description:  Abnormal brain morphology demonstrated by expansion in 4th ventricle volume
Exp Paradigm:  Volumetric analyses of in-vivo Magnetic Resonance Imaging
  Magnetic resonance imaging (MRI)
  12 weeks
  DTI: Fractional anisotropy or Relative anisotropy in brain regions 2
  Abnormal
Description:  Abnormal brain microstructure indicated by increased fractional anisotrophy in left and right stria medullaris, amygdala/piriform area
Exp Paradigm:  Voxel Based Morphometric analysis of diffusion tensor imaging (DTI)
  Diffusion tensor imaging
  12 weeks
  DTI: Fractional anisotropy or Relative anisotropy in brain regions 2
  Abnormal
Description:  Abnormal brain microstructure indicated by decreased fractional anisotrophy in left amygdala, cerebral peduncles, right fimbria, right ventral subicular regions
Exp Paradigm:  Voxel Based Morphometric analysis of diffusion tensor imaging (DTI)
  Diffusion tensor imaging
  12 weeks
Brain morphology1
 No Change
 Magnetic resonance imaging (MRI)
 12 weeks
Brain size1
 No Change
 Magnetic resonance imaging (MRI)
 12 weeks
Myelination2
 No Change
 Immunohistochemistry
 Unreported
Sensorimotor gating1
 No Change
 Prepulse inhibition
 12 weeks
 Not Reported: Circadian sleep/wake cycle ,   Communications ,   Developmental profile ,   Emotion ,   Homeostasis ,   Immune response ,   Learning & memory ,   Maternal behavior ,   Molecular profile ,   Motor phenotype ,   Neurophysiology ,   Repetitive behavior ,   Seizure ,   Sensory ,   Social behavior ,  

POLYIC_4_IN_B

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
  DTI: Fractional anisotropy or Relative anisotropy in brain regions 1
  Abnormal
Description:  Abnormal brain microstructure indicated by decreased fractional anisotrophy in left amygdala, cerebral peduncles, right fimbria, anterior cingulate, ventrial striatum and external capsule
Exp Paradigm:  Voxel Based Morphometric analysis of diffusion tensor imaging (DTI)
  Diffusion tensor imaging
  12 weeks
  Myelination 1
  Decreased
Description:  Decreased staining of CNPase in external capsule and left fimbria
Exp Paradigm:  Immunohistochemical analysis of oligodendrocyte marker CNPase of coronal sections
  Immunohistochemistry
  Unreported
  DTI: Fractional anisotropy or Relative anisotropy in brain regions 1
  Abnormal
Description:  Abnormal brain microstructure indicated by increased fractional anisotrophy in left stria medullaris, left fimbria, lateral septal area and prefrontal lobe
Exp Paradigm:  Voxel Based Morphometric analysis of diffusion tensor imaging (DTI)
  Diffusion tensor imaging
  12 weeks
 Not Reported: Circadian sleep/wake cycle ,   Communications ,   Developmental profile ,   Emotion ,   Homeostasis ,   Immune response ,   Learning & memory ,   Maternal behavior ,   Molecular profile ,   Motor phenotype ,   Neurophysiology ,   Repetitive behavior ,   Seizure ,   Sensory ,   Social behavior ,  

POLYIC_5_IN_B

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
  Stereotypy 1
  Increased
Description:  Increased repetitive/compulsive behavior
Exp Paradigm:  Marble Burying Test
  Marble-burying test
  12 weeks
  Self grooming: perseveration 1
  Increased
Description:  Increased self grooming behavior indicative of repetitive/stereotypic behavior
Exp Paradigm:  Grooming behavior assessments in small glass beaker
  Grooming behavior assessments
  13 weeks
  Social interaction 1
  Decreased
Description:  Decreased sociability indicated by decreased preference for social chamber
Exp Paradigm:  Three chamber apparatus
  Three-chamber social approach test
  10 weeks
  Mating behavior 1
  Decreased
Description:  Decreased female-induced scent marking
Exp Paradigm:  Scent Marking Test
  Scent marking test
  11 weeks
  Ultrasonic vocalization 1
  Decreased
Description:  Decreased ultrasonic vocalizations (UsV) in presence of female and decreased number of two frequency step and chevron syllables
Exp Paradigm:  Male mice: UsV response to female stimuli
  Monitoring ultrasonic vocalizations: reciprocal social interaction test
  8-9 weeks
  Ultrasonic vocalization 1
  Decreased
Description:  Decreased ultrasonic vocalizations (UsV) in response to isolation and decreased number of harmonic syllables and more short and complex syllables
Exp Paradigm:  UsV vocalization in response to maternal separation along with structural analysis of UsV
  Monitoring ultrasonic vocalizations: maternal separation
  10 days
  Ultrasonic vocalization 1
  Decreased
Description:  Decreased ultrasonic vocalizations (UsV) in presence of female and decreased number of two frequency step syllables
Exp Paradigm:  Male mice: UsV response to male stimuli
  Monitoring ultrasonic vocalizations: reciprocal social interaction test: male-female
  8-9 weeks
Size/growth1
 No Change
 General observations
 Unreported
Nest relocation1
 No Change
 General observations
 Unreported
Pup retrieval1
 No Change
 Pup retrieval assay
 Unreported
Ear twitch reflex or Preyer's reflex1
 No Change
 Negative geotaxis test; Grasping reflex test; Righting reflex test
 Unreported
Olfaction1
 No Change
 Olfactory discrimination test
 13-14 weeks
 Not Reported: Circadian sleep/wake cycle ,   Emotion ,   Homeostasis ,   Immune response ,   Learning & memory ,   Molecular profile ,   Motor phenotype ,   Neuroanatomy / Ultrastructure / Cytoarchitecture ,   Neurophysiology ,   Seizure ,  

POLYIC_7_IN_B

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
  Repetitive digging 1
  Increased
Description:  increased levels of stereotypic marble burying behavior
Exp Paradigm:  Marble Burying Test
  Marble-burying test
  Unreported
  Repetitive digging 2
  Increased
Description:  MIA offspring have increased stereotyped marble burying compared to controls
  Marble-burying test
  6 weeks
  Sensorimotor gating 1
  Decreased
Description:  Decreased prepulse inhibition of startle reflex
Exp Paradigm:  PPI (prepulse inhibition) of the acoustic startle reflex
  Prepulse inhibition
  Unreported
  Sensorimotor gating 2
  Decreased
Description:  MIA offspring exhibit decreased PPI response to 5 or 15 db prepulses
  Prepulse inhibition
  6 weeks
  Social interaction 1
  Decreased
Description:  Decreased social preference as assessed by reduced duration spent and entries into chamber housing novel vs. familiar mouse
Exp Paradigm:  Social preference test
  Three-chamber social approach test
  Unreported
  Social approach 2
  Decreased
Description:  MIA offspring have deficits in preferring to interact with an unfamiliar mouse over a familiar mouse
  Three-chamber social approach test
  6 weeks
  Social approach 2
  Decreased
Description:  MIA offspring have deficits in sociability or preference to interact with a novel mouse over a novel object
  Three-chamber social approach test
  6 weeks
  Ultrasonic vocalization 2
  Decreased
Description:  MIA offspring exhibit deficits in communication and have reduced number and duration of ultrasonic vocalization
 
  6 weeks
  Anxiety 2
  Increased
Description:  MIA offspring had fewer entries and time spent in the center of the arena
Exp Paradigm:  Time spent in the center was used to assess anxiety like behavior
  Open field test
  6 weeks
  Anxiety 1
  Increased
Description:  Increased anxiety indicated by reduced duration spent, and entries into, center arena
Exp Paradigm:  Open Field test
  Open field test
  Unreported
  Intestinal microbiota composition 2
  Abnormal
Description:  MIA offspring have dysbiosis because of alterations in the composition of gut bacteria, specifically, classes of Clostridia and Bacteroidia .
  16S rRNA gene sequence analysis for identification of bacteria
  Unreported
  Homeostasis 2
  Decreased
Description:  MIA offspring show deficits in intestinal integrity starting as early as 3 weeks that continues through adulthood
  Intestinal permeability test
  3 weeks, adult
  Adaptive immune response: T cells 1
  Decreased
Description:  Decreased splenic CD4 Foxp3 CD25 regulatory T cells
Exp Paradigm:  Flow Cytometry analysis of splenocytes stimulated with PMA/ionomycin in the presence of GolgiPLUG
  Flow cytometric analysis
  Unreported
  Cytokine levels 2
  Increased
Description:  MIA offspring have increased levels of interleukin-6 in the colon
 
  Unreported
  Immunosuppression 1
  Increased
Description:  Increased populations of Gr-1hi CD11b+ Ly6Cmid Ly6Ghi SSCmid, Gr-1mid CD11b+ Ly^Cmid Ly6Gmid SSCmid, and Gr-1mid CD11b+ Ly6Chi Ly6G- SSClo
Exp Paradigm:  Flow cytometry analysis
  Flow cytometric analysis
  Unreported
  Adaptive immune response: T cells 1
  Decreased
Description:  Decreased levels of total CD4+ Foxp3+ cells, CD4+ Foxp3+ CD25- T cells, total CD4+ Foxp3+, Foxp3+ CD25-, and Foxp3+ CD25+ cells in mesenteric lymph nodes
Exp Paradigm:  Flow cytometry analysis
  Flow cytometric analysis
  Unreported
  Cytokine levels 2
  Decreased
Description:  MIA offspring express decreased levels of cytokines and chemokines and MIP1-alpha
 
  Unreported
  Cytokine levels 2
  Decreased
Description:  Treatment with B. fragilis normalizes the expression of colon IL-6 mRNA and protein levels
 
  Unreported
  Innate immune response 1
  Abnormal
Description:  Abnormal major leukocyte classes indicated by higher level of Gr-1+ and CD11b+; No Change in total B220+ B cells, NK1.1+ NK cells, CD4+ T cells, or CD8+ T cells
Exp Paradigm:  Flow cytometry analysis
  Flow cytometric analysis
  Unreported
  Regulation of gene expression 2
  Decreased
Description:  MIA exposed offspring have decreased expression of TJP1, TJP2, OCLN and CLDN8
Exp Paradigm:  Gene Regulation
  Quantitative PCR (qRT-PCR)
  Adult
  Regulation of gene expression 2
  Increased
Description:  MIA exposed offspring have increased expression of CLDN15
Exp Paradigm:  Gene Regulation
  Quantitative PCR (qRT-PCR)
  Adult
Adaptive immune response: T cells1
 No Change
 Flow cytometric analysis
 Unreported
 Not Reported: Circadian sleep/wake cycle ,   Communications ,   Developmental profile ,   Homeostasis ,   Learning & memory ,   Maternal behavior ,   Molecular profile ,   Motor phenotype ,   Neuroanatomy / Ultrastructure / Cytoarchitecture ,   Neurophysiology ,   Seizure ,  

POLYIC_7_IN_B_BM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
  General locomotor activity 1
  Side Effect
Description:  Increased in locomotor activity (distance traveled) as a side effect of the treatment
Exp Paradigm:  Open Field test
  Open field test
  17-19 weeks
  Repetitive digging 1
  Restored
Description:  Increased levels of repetitive marble burying behavior is restored to the same level as saline controls
Exp Paradigm:  Marble Burying Test
  Marble-burying test
  17-19 weeks
  Social interaction 1
  Refractory
Description:  Decreased social preference (reduced duration spent and entries into chamber housing novel vs. familiar mouse) is refractory to the treatment
Exp Paradigm:  Social preference test
  Three-chamber social approach test
  17-19 weeks
  Anxiety 1
  Restored
Description:  Increased anxiety levels (increased number and decreased time spent of center entries) is restored to the same level as saline controls
Exp Paradigm:  Open Field test
  Open field test
  17-19 weeks
  Cytokine levels 1
  Restored
Description:  IL-6 and IL-17 secreted by isolated splenic CD4+ T cells (in response to phorbol 12-myristate 13-acetate) is restored to the same level as saline controls
Exp Paradigm:  Flow cytometry analysis
  Flow cytometric analysis
  19-20 weeks
  Adaptive immune response: T cells 1
  Restored
Description:  Decreased splenic regulatory T cells (CD4+ TCRbeta+ CD25+ Foxp3+) is restored to the same level as saline controls
Exp Paradigm:  Flow Cytometry analysis of splenocytes stimulated with PMA/ionomycin in the presence of GolgiPLUG
  Flow cytometric analysis
  19-20 weeks
  Immunosuppression 1
  Restored
Description:  Increased splenic Gr-1+ cells is restored to the same level as saline controls
Exp Paradigm:  Flow cytometry analysis
  Flow cytometric analysis
  19-20 weeks
 Not Reported: Circadian sleep/wake cycle ,   Communications ,   Developmental profile ,   Homeostasis ,   Learning & memory ,   Maternal behavior ,   Molecular profile ,   Neuroanatomy / Ultrastructure / Cytoarchitecture ,   Neurophysiology ,   Seizure ,   Sensory ,  

POLYIC_7_IN_B_BM_S

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
  General locomotor activity 1
  Side Effect
Description:  Increased in locomotor activity (distance traveled) as a side effect of the treatment
Exp Paradigm:  Open Field test
  Open field test
  4 months
  Repetitive digging 1
  Restored
Description:  Increased levels of repetitive marble burying behavior is restored to the same level as saline controls
Exp Paradigm:  Marble Burying Test
  Marble-burying test
  4 months
  Social interaction 1
  Refractory
Description:  Decreased social preference (reduced duration spent and entries into chamber housing novel vs. familiar mouse) is refractory to the treatment
Exp Paradigm:  Social preference test
  Three-chamber social approach test
  4 months
  Anxiety 1
  Restored
Description:  Increased anxiety levels (increased number and decreased time spent of center entries) is restored to the same level as saline controls
Exp Paradigm:  Open Field test
  Open field test
  4 months
  Cytokine levels 1
  Restored
Description:  IL-6 and IL-17 secreted by isolated splenic CD4+ T cells (in response to phorbol 12-myristate 13-acetate) is restored to the same level as saline controls
Exp Paradigm:  Flow cytometry analysis
  Flow cytometric analysis
  4.5 months
  Adaptive immune response: T cells 1
  Restored
Description:  Decreased splenic regulatory T cells (CD4+ TCRbeta+ CD25+ Foxp3+) is restored to the same level as saline controls
Exp Paradigm:  Flow Cytometry analysis of splenocytes stimulated with PMA/ionomycin in the presence of GolgiPLUG
  Flow cytometric analysis
  4.5 months
  Immunosuppression 1
  Restored
Description:  Increased splenic Gr-1+ cells is restored to the same level as saline controls
Exp Paradigm:  Flow cytometry analysis
  Flow cytometric analysis
  4.5 months
 Not Reported: Circadian sleep/wake cycle ,   Communications ,   Developmental profile ,   Homeostasis ,   Learning & memory ,   Maternal behavior ,   Molecular profile ,   Neuroanatomy / Ultrastructure / Cytoarchitecture ,   Neurophysiology ,   Seizure ,   Sensory ,  

POLYIC_8_IN_B

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
  Stereotypy 1
  Increased
Description:  Increased repetitive behavior shown by burying of higher percentage of marbles
Exp Paradigm:  Marble Burying Test
  Marble-burying test
  Unreported
  Social approach 1
  Decreased
Description:  Decreased social approach indicated by decreased preference for chamber containing novel mouse
Exp Paradigm:  Three chamber social approach
  Three-chamber social approach test: sociability
  10 weeks
  Social interaction 1
  Decreased
Description:  Decreased social sniffing measured by time spent sniffing novel mouse
Exp Paradigm:  Three chamber social approach
  Three-chamber social approach test: sociability
  10 weeks
  Self grooming: social context 1
  Increased
Description:  Increased time spent grooming
Exp Paradigm:  Male mice: grooming behavior observations
  Grooming behavior assessments
  Unreported
  Social interaction 1
  Decreased
Description:  Decreased sociability determined by difference between time spent in chamber with novel mouse vs. object
Exp Paradigm:  Three chamber social approach
  Three-chamber social approach test: sociability
  10 weeks
  Ultrasonic vocalization 1
  Increased
Description:  Increased number of ultrasonic vocalizations
Exp Paradigm:  Maternal pup sepration ultrasonic vocalization
  Monitoring ultrasonic vocalizations: maternal separation
  P8, P10
  Cytokine levels 1
  Abnormal
Description:  Abnormal immune response indicated by higher levels of IL-17 and IL-10
Exp Paradigm:  Splenocyte response to stimulation by phorbol myristate acetate/ionomycin
  Stimulation of immune cells: splenocytes
  Unreported
Cytokine levels1
 No Change
 Stimulation of immune cells: splenocytes
 Unreported
Self grooming: social context1
 No Change
 Grooming behavior assessments
 Unreported
 Not Reported: Circadian sleep/wake cycle ,   Developmental profile ,   Emotion ,   Homeostasis ,   Learning & memory ,   Maternal behavior ,   Molecular profile ,   Motor phenotype ,   Neuroanatomy / Ultrastructure / Cytoarchitecture ,   Neurophysiology ,   Seizure ,   Sensory ,  

POLYIC_10_IN_B

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Motor coordination and balance1
 No Change
 Accelerating rotarod test
 8 weeks
 Not Reported: Circadian sleep/wake cycle ,   Communications ,   Developmental profile ,   Emotion ,   Homeostasis ,   Immune response ,   Learning & memory ,   Maternal behavior ,   Molecular profile ,   Neuroanatomy / Ultrastructure / Cytoarchitecture ,   Neurophysiology ,   Repetitive behavior ,   Seizure ,   Sensory ,   Social behavior ,  

POLYIC_9_IN_B

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
  Motor coordination and balance 1
  Decreased
Description:  Decreased motor coordination as measured by latency to fall
Exp Paradigm:  Male mice: Rotarod test
  Accelerating rotarod test
  8 weeks
  Neuronal number: Purkinje cells 1
  Increased
Description:  Increased Purkinje cell loss in Lobule VII of cerebellar vermis
Exp Paradigm:  Quantitative analysis of Purkinje cell loss
  Histology
  16 weeks
  Synaptic morphology 1
  Abnormal
Description:  Abnormal cerebral synaptosome indicated by unidentified electron-dense matrix material; fragile post-synaptic densities
Exp Paradigm:  Transmission electron microscopy of cerebral synaptosomes
  Electron microscopy
  Unreported
  Social interaction 1
  Decreased
Description:  Decreased social preference
Exp Paradigm:  Male mice: Three chamber apparatus
  Three-chamber social approach test
  8 weeks
  Core body temperature 1
  Decreased
Description:  Decreased basal body temperature indicative of relative hypothermia
 
  8 weeks
  Mitochondrial function 1
  Increased
Description:  Increased mitochondrial respiratory chain activity of Complex ! And Complex IV
Exp Paradigm:  Respiratory chain enzymology of purified cerebral mitochondria
  Mitochondrial respiratory chain enzyme analysis
  Unreported
  Protein expression level evidence 1
  Decreased
Description:  Decreased expression of P2Y2 and P2X7 in cerebral synaptosomes
Exp Paradigm:  Purinergic Receptor Expression
  Western blot
  Unreported
  Signaling 1
  Decreased
Description:  Decreased phosphorylation of ERK1 and ERK2 and CAMKII
Exp Paradigm:  Erk1/2 And Camkii Signaling
  Western blot
  16 weeks
  Protein expression level evidence 1
  Decreased
Description:  Decreased FMRP deficits in syaptosomes
Exp Paradigm:  Fmrp Expression
  Western blot
  16 weeks
Adaptive immune response: B cells antibody production1
 No Change
 Antibody levels
 15 weeks
Protein expression level evidence1
 No Change
 Western blot
 16 weeks
 Not Reported: Circadian sleep/wake cycle ,   Communications ,   Developmental profile ,   Emotion ,   Immune response ,   Learning & memory ,   Maternal behavior ,   Neurophysiology ,   Repetitive behavior ,   Seizure ,   Sensory ,  

POLYIC_11_IN_B

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
  Cortical lamination 1
  Decreased
Description:  Cortical cytoarchitecture is disorganized, with 'intrusions' and 'protrusions', in offspring exposed to MIA, detected using markers: SATB2 (a marker for postmitotic neurons), TBR1(marker for deep cortical layers) and CTIP2 show disorganized expression
  Immunohistochemistry
  E14.5, E18.5
  Repetitive digging 1
  Increased
Description:  Offspring exposed to MIA display increased number of marbles buried indicating increase in repetitive behavior
  Marble-burying test
  Adult
  Social approach 1
  Decreased
Description:  Offspring exposed to MIA have reduced social preference to novel stimulus mouse
  Three-chamber social approach test
  Adult
  Ultrasonic vocalization: Isolation induced 1
  Increased
Description:  Offspring of mothers injected with poly(I:C) have increased usv upon separation from mother
  Monitoring ultrasonic vocalizations: manual count
  P7-P9
  Cytokine levels: pro-inflammatory 1
  Increased
Description:  Increased levels of interleukin-17a (IL-17a) are seen in the sera from poly(I:C) injected pregnant mice
  ELISA
  E14.5
  Gene expression 1
  Increased
Description:  Increased levels of IL-17a are detected in the fetal brains of offspring exposed to MIA
  In situ hybridization (ISH)
  E14.5
  Marker expression 1
  Decreased
Description:  Decreased expression of markers specific to layers of the cortex are detected, starting in the fetal brains through adulthood: SATB2 (a marker for postmitotic neurons), TBR1(marker for deep cortical layers) and CTIP2 show disorganized expression
  Immunohistochemistry
  E14.5, E18.5, adult
Size/growth1
 No Change
 Body weight measurement
 3-3.7 months
Reproductive function1
 No Change
 
 3-3.7 months
Cytokine levels: anti-inflammatory1
 No Change
 ELISA
 E14.5
General locomotor activity1
 No Change
 Three-chamber social approach test: distance traveled
 Adult
Cortical thickness1
 No Change
 Immunohistochemistry
 E18.5
 Not Reported:

POLYIC_6_IN_B_IL6_KO_rIL17a

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
  Ultrasonic vocalization: Isolation induced 1
  Increased
Description:  Injection of recombinant IL-17a into fetal brains of embryos in IL-6 KO mothers induces increased USV calls, similar to poly(I:C) injection in WT mothers, in the offspring: this overrides the IL-6 KO genetic background indicating that IL-17a mediates ASD related phenotype in this scenario
  Monitoring ultrasonic vocalizations: manual count
 
 Not Reported:

POLYIC_17_IN_B

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
  Intrinsic membrane properties 1
  Increased
Description:  Membrane excitability is increased as rheobase is decreased in PV neurons from adult MIA
  Whole-cell patch clamp: parvalbumin (PV) interneurons
  Adult
  Spontaneous post synaptic event amplitude: inhibitory currents 1
  Decreased
Description:  Spontaneous IPSC amplitude is also reduced in the pyramidal cells from the PrL region of the mPFC in the slices from MIA offspring compared to WT
  Whole-cell patch clamp: pyramidal cells in slices containing prelimbic region(PrL) of the medial prefrontal cortex(mPFC)
  3-3.3 months
  Event related oscillations (EROs) in electroencephalography (EEG) 1
  Decreased
Description:  High gamma activity was not correlated to time spent In axiogenic open arms of the elevated-plus maze in adult MIA offspring as the gamma power was observed to be similar whether they were in the open or closed arms, unlike WT where the correlation is observed
Exp Paradigm:  In vivo local field potential (LFP) recordings
 
  Adult
  Miniature post synaptic current frequency: inhibitory 1
  Decreased
Description:  Evoked mIPScs have decreaed frequency in the pyramidal cells from the PrL region of the mPFC in the slices from MIA offspring compared to WT
  Whole-cell patch clamp: pyramidal cells in slices containing prelimbic region(PrL) of the medial prefrontal cortex(mPFC)
  Adult
  Spontaneous post synaptic event frequency: inhibitory currents 1
  Decreased
Description:  Spontaneous IPSC frequency is reduced in the pyramidal cells from the PrL region of the mPFC in the slices from MIA offspring compared to WT
  Whole-cell patch clamp: pyramidal cells in slices containing prelimbic region(PrL) of the medial prefrontal cortex (mPFC)
  3-3.3 months
  Anxiety 1
  Increased
Description:  Adult MIA offspring spend less time in anxiogenic open arms of the elevated plus maze
  Elevated plus maze test
  Adult
  Cognitive flexibility: Associative learning 1
  Decreased
Description:  MIA offspring take much longer to learn the change in cue that predicts reward in the set shifting trial than WT controls
  Set-shifting task
  3-3.3 months
  Protein expression level evidence 1
  Decreased
Description:  Levels of GAD67 the enzyme that synthesizes GABA is reduced in parvalbumin positive cells from MIA offspring
  Immunohistochemistry: GAD67 levels in prelimbic region(PrL) of the medial prefrontal cortex (mPFC)
 
Reward reinforced choice behavior1
 No Change
 Operant conditioning paradigm; Delayed non-match to sample T-maze test
 3-3.3 months
Neuronal number: Interneurons1
 No Change
 Stereology
 Adult
Synapse density: Inhibitory1
 No Change
 Immunohistochemistry
 Adult
Synaptic morphology1
 No Change
 Immunohistochemistry
 Adult
Intrinsic membrane properties1
 No Change
 Whole-cell patch clamp: parvalbumin (PV) interneurons
 Adult
Miniature post synaptic current amplitude: inhibitory1
 No Change
 Whole-cell patch clamp: pyramidal cells in slices containing prelimbic region(PrL) of the medial prefrontal cortex(mPFC)
 3-3.3 months
 Not Reported:

POLYIC_17_IN_B_PV-ChR2

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
  Presynaptic function: paired-pulse facilitation 1
  Decreased
Description:  MIA offspring have decreased paired pulse depression as well between PV interneurons and their target pyramidal neurons observed using channel rhodopsin optogenetics
  Optogenetics; Light-evoked postsynaptic currents
  3-3.3 months
  Synaptic transmission: inhibitory 1
  Decreased
Description:  MIA offspring have decreased GABAergic transmission from prefrontal PV interneurons to pyramidal cell targets observed using channel rhodopsin activated optogenetically in PV interneurons
  Optogenetics; Light-evoked postsynaptic currents
  3-3.3 months
 Not Reported:
HELP