Table 2.

Summary of reports on the CX3CL1–CX3CR1 axis protein levels and mRNA expression in the studies using maternal immune activation paradigm with LPS or Poly I:C

MIA induction agent	Sex, strain and species	CX3CL1–CX3CR1 axis	Additional information	References
LPS	Male Wistar rats	↑ Cx3cl1 (hippocampus), ≡ Cx3cl1 (frontal cortex) and Cx3cr1 (hippocampus, frontal cortex), ↑ CX3CL1 (frontal cortex) and CX3CR1 (hippocampus), ≡ CX3CL1 (hippocampus) and CX3CR1 (frontal cortex) in young offspring ↓ CX3CL1 (hippocampus), ≡ CX3CL1 (frontal cortex) and CX3CR1 (hippocampus, frontal cortex) in adult offspring	Alterations in the mRNA expression of microglial markers and the profile of cytokines released in the brains of young offspring Behavioral schizophrenia-like disturbances (e.g., PPI deficits and an aggressive phenotype) in adulthood	[172]
Poly I:C		≡ Cx3cl1 and Cx3cr1 (hippocampus, frontal cortex), ↑ CX3CL1 (frontal cortex), ≡ CX3CL1 (hippocampus), ↓ CX3CR1 (hippocampus), ≡ CX3CR1 (frontal cortex) in young offspring ↑ CX3CL1 (frontal cortex), ≡ CX3CL1 (hippocampus) and CX3CR1 (hippocampus, frontal cortex) in adult offspring
LPS	Male Sprague–Dawley rats	≡ Cx3cl1 and Cx3cr1 (hippocampus, frontal cortex) in adult offspring ≡ CX3CL1 and CX3CR1 (hippocampus, frontal cortex) in adult offspring with a deficit in PPI ↓ CX3CL1 (frontal cortex) and CX3CR1 (hippocampus), ≡ CX3CL1 (hippocampus) and CX3CR1 (frontal cortex) in adult offspring without a deficit in PPI ↓ CX3CL1 (hippocampus) in offspring with PPI deficit after additional challenge with LPS in adulthood ↓ CX3CR1 (frontal cortex) in offspring without PPI deficit after additional challenge with LPS in adulthood	Behavioral schizophrenia-like changes (increased exploratory activity and anxiety-like behaviors) in adulthood Occurrence of two phenotypes in PPI (with and without deficit) Adult offspring were additionally exposed to the acute challenge with LPS in adulthood, according to the “two-hit” hypothesis of schizophrenia	[173]
Poly I:C	Male Sprague-Dawley rats	↓ Cx3cl1 and Cx3cr1 (hippocampus), ≡ Cx3cl1 and Cx3cr1 (frontal cortex) in adult offspring with a deficit in PPI ≡ Cx3cl1 and Cx3cr1 (hippocampus, frontal cortex) in adult offspring without a deficit in PPI ↓ Cx3cr1 (frontal cortex) in adult offspring without PPI deficit after additional challenge with Poly I:C in adulthood ≡ CX3CL1 and CX3CR1 (hippocampus, frontal cortex) in adult offspring with a deficit in PPI ↑ CX3CL1 and CX3CR1 (frontal cortex), ≡ CX3CL1 and CX3CR1 (hippocampus) in adult offspring without a deficit in PPI ↓ Cx3cr1 (frontal cortex) in offspring without PPI deficit after additional challenge with Poly I:C in adulthood ↑ CX3CL1 (hippocampus) in offspring without PPI deficit after additional challenge with Poly I:C in adulthood	Behavioral schizophrenia-like disturbances (diminished number of aggressive interactions, depressive-like episodes, increased exploratory activity) Occurrence of two phenotypes in PPI (with and without deficit) Adult offspring were additionally exposed to the acute challenge with Poly I:C in adulthood, according to the “two-hit” hypothesis of schizophrenia	[174]
Poly I:C	Male C57BL/6 mice	↓ Cx3cr1 (microglial cells isolated from the hippocampus) in adult offspring	Deficits in social behavior and PPI (in part of animals) as well as working memory impairment	[175]
Poly I:C	Female and male BALB/c mice	↑ Population of microglia (isolated from complete brains) expressing CX3CR1 in young female offspring that did not persist until adulthood ↓ CX3CR1 level in male offspring both in adolescence and adulthood	Deficits in PPI only in adult female offspring	[176]
Poly I:C	Female and male C57BL/6 mice	≡ Cx3cl1 and Cx3cr1 (ventromedial prefrontal cortex, hippocampal dentate gyrus and cerebellum)	Partly sex-dependent behavioral schizophrenia-like disturbances (for instance increased repetitive behavior, anxiety, reduced sociability and deficits in PPI)	[177]
Poly I:C	Male C57BL/6 mice	Age-specific changes in Cx3cr1 expression: ↓ at birth and P14, ↑ at P7 and P60	Cx3cr1 expression was particularly up-regulated at the beginning of synaptogenesis (P7) and declined during the peak of this process and spine formation (P14)	[178]
Poly I:C	Female and male chimeric and transgenic mice	CX3CR1-highly expressing monocytes	Dendritic spine loss, impairments in learning-dependent dendritic spine formation and deficits in learning tasks	[182]
High-fat diet	Female and male C57BL/6N	↓ Cx3cr1 (hippocampus) in adolescent male offspring ≡ Cx3cr1 (hippocampus) in adolescent female offspring	Similar phenotypes in both sexes for IL-6-driven immune priming and microglial morphology Sex-dependent changes in transcriptomic and astrocyte-microglia interaction	[183]

↑ (increased), ↓ (decreased), ≡ (unchanged)