Table 2.

Outcomes of offspring after inducing MIA by Poly I:C

Animals	Dose and Injection Day	Outcomes	Notes	Refs.
BALB/c mice	20 mg/kg GD9	– Differences in species richness microbiome – ♂ Offspring: ↑ Abundance of four families of Firmicutes phylum – ♀ Offspring: ↑ Abundance of Lactobacillaeles ↓ Abundance of Prevotellaceae and Porpyromonadaceae	Differential bacterial findings P30 correspond with activation immune system, strong increase in microglial cells	(52)
C57BL/6 mice	20 mg/kg GD12	Preferential to Th17 cell differentiation of lymphocytes	Adaptive immune system	(53)
C57BL/6J mice	20 mg/kg GD12.5	– Behavioral impairments – Adult splenocytes: ↓ Mitochondrial ATP production	Lower complex I activity Long-lasting effects bioenergetics splenocytes	(54)
C57BL/6J mice	5 mg/kg GD15–17	– ↓ Growth and sensorimotor development – Fetal brain: ↑ IL-2, IL-5, and IL-6 cytokines ↑ Metabotropic receptor 5: mGluR5	MIA induced by LPS in parallel (see Table 1)	(33)
C57BL6/J mice	5 mg/kg GD9	– Juvenile cortex: Hypoacetylation of histone H3 and H4 ↓ Promotor-specific histone acetylation (Gria1, Slc17a7) – Juvenile hippocampus: ↑ Disc1 and Ntrk3 genes – Adult offspring: Behavioral abnormalities No changes in histone acetylation ↓ Promotor-specific histone acetylation (Gria1, Slc17a7)	Early epigenetic changes contribute to delayed behavioral abnormalities in adult offspring	(55)
C57BL/6J mice	5 mg/kg GD9.5	Adult frontal cortex: – Activated innate immune receptor TLR3 signaling pathway – Oxidative/nitrosative stress – Accumulation of proinflammatory mediators (Nfkb and iNOS)	Chronic paliperidone: – Blocked neuroinflammatory response – Stimulate M2 polarization microglia – ↑ Spatial working memory	(56)
C57BL/6J mice	5 mg/kg GD9 or GD17	– Neuroanatomical alterations – Behavioral alterations – ↓ Brain volume – ↓ Glucose preferences		(57)
C57BL/6N mice	5 mg/kg GD9	Hypomethylation of adult brain	n-3 PUFA intervention reduces outcomes	(58)
C57BL/6J mice	20 mg/kg GD12.5	– Activation of local circuit interneurons adult brain – ↑ Synaptic strength adult brain	Alterations in flow of signals within the mPFC to basolateral amygdala pathway	(59)
C57BL/6J mice	20 mg/kg GD12	– Neonate immune organs and brain: – ↑ Cytokine levels of TNFα and IL-18 – Adult: Alteration in behavioral responses		(19)
C57BL/6J mice	20 mg/kg GD12.5	– ♂ Offspring: ↓ mRNA and protein levels of TNFα/iNOS, IL-6/IL-1B, anti-inflammatory factors – ♀ Offspring: ↑ mRNA and protein levels of TNFα/iNOS, IL-6/IL-1β, anti-inflammatory factors		(60)
C57BL/6J mice	20 mg/kg GD12.5	Fetal and placental sex influenced: – Responses of immune genes to metabolic and inflammatory stress.	Gene pathways: ♂ P53 feedback and Wnt signaling ♀ TGF-β and Insulin/IGF/MAPK	(61)
C57BL/6 mice	20 mg/kg GD12.5	– ↑ CCL5 and CXCL10 fetal brain – ↑ Cytokines/chemokines in Map2k7 Hz mice	JNK signaling	(62)
C57BL/6J mice	20 mg/kg GD12	– Neonate immune organs and brain: ↑ Cytokine levels of TNFα and IL-18 – Adult: Alteration in behavioral responses		(19)
C57BL/6J mice	5 mg/kg/mL GD9	Fetal brains: – Dysregulation in brain development-related gene pathways – ↑ RNA-editing	Gene pathways: – Brain and neuronal development – Energy and metabolism – Immunological signatures	(63)
CD-1 mice	5 mg/kg GD12.5, 17.5	– ♂ Offspring: Alteration in social interaction ↑ Nrg1 and Erbb4 gene expression – Adult: Behavioral changes	NRG-ErbB signaling pathway Behavioral changes are time-related and sex-specific	(64)
Sprague-Dawley rats	10 mg/kg GD9	– Age-related behavioral and neuro-inflammatory changes – Activation of microglia Astrocytes activated at PND60		(65)
Sprague-Dawley rats	10 mg/kg GD14	Fetal brains: – ↑ Amino acid transporters – ↓ Snat5, Eaat1, and Glyt gene expression		(66)
Sprague-Dawley rats	10 mg/kg GD17	– Depressive-like behavior – Dendrite development obstruction – ↑ Isg15 expression brain	NEDD4/Rap2A signaling	(67)
Sprague-Dawley rats	20 mg/kg GD12	– ↑ Anxiety-like behaviors – ↓ Social behaviors – Brain: ↑ Lipid peroxidation ↓ Total antioxidant content ↑ Inflammatory genes: Tnfa, Il6, Il1b ↑ Apoptotic genes: Bax, Cas3, Cas9 ↓ Neuroprotective genes: Bdnf, Bcl2	MIA induced by LPS in parallel (see Table 1)	(48)
Wistar rats	4 mg/kg Early = GD10 Late = GD19	♂ Offspring: – Sensorimotor gating deficits – ↑ D1r gene expression in nucleus accumbens	Schizophrenia-like phenotypes	(68)
Wistar rats	5 mg/kg GD10 and GD9	Fetal brains: – Dysregulation in brain development-related gene pathways – ↑ RNA editing Neonates: – ↑ lymphoid aggregates – Altered intestinal inflammatory profile – Disruption in GI barrier tight junction protein Adults: – ↑ Anxiety-like behavior	Gene pathways: – Brain and neuronal development – Energy and metabolism	(69)
Wistar rats	10 mg/kg GD15	– ↓ Litter size depending on Poly I:C supplier – ↓ Placenta weight ♂ Offspring: – ↓ Fetal brain weight	Outcome depending on Poly I:C supplier and endotoxin concentration.	(70)

GD, gestational days; LPS, lipopolysaccharide; MIA, maternal immune activation; Poly I:C, polyinosinic:polycytidylic acid; PUFA, polyunsaturated fatty acid; TLR3, Toll-like receptor 3. HPA, hypothalamic-pituitary-adrenal; PDTC, pyrrolidine dithiocarbamate; mPFC, medial prefrontal cortex; GI, Gastrointestinal; CAMs, cell adhesion molecules; PND, postnatal day; CCL5, chemokine (C-C motif) ligand 5; CXCL10, C-X-C motif chemokine ligand 10; ↑, increase; ↓, decrease; ♂, male; ♀, female.