TABLE 3.

Principal findings of stress model studies included in this review.

	Animal model	Author	Specie	Sex	Age	Behavior characterization	Methods	Analysis	Results	Rescue experiments	Reelin alteration
Stress models	Maternal deprivation	Aksic et al., 2021	Rat	Male and female	P60		Rat offsprings with maternal deprivation from P9 to P10.	Immunohistochemistry (PV and reelin). Dell death assay.	Reduced number of PV positive interneurons in CA1 (HP) and PFC. Reduced number of reelin positive interneurons in CA1 and CA3 (HP), but unaltered in neocortex. No differences in cell death.		↓ reelin positives cells in HP
	Social isolation	Ko et al., 2016	Rat	Male and female	3 and 7-week-old	locomotion and PPI	Rat offspring isolated at P21 and mated with social rats. Offsprings of 2 next generation evaluated.	qPCR (monoamines and schizophrenia-related genes in mPFC and HP). Behavioral characterization.	Impaired PPI in second generation of rats. Lower levels of dopamine and serotonine in mPFC and HP in the third generation. Female isolation rats presented elevated reelin gene expression levels in PFC with respect to non-isolation rats in the third generation.		↑ reelin gene expression levels in PFC
	PRS	Matrisciano et al., 2013	Mouse	Male	P1, p7, p14, p60	open field, social behavior, PPI and fear conditioning	Mouse offspring exposed to PRS (30 min, 2 times per day, from E7 to E21)	RT-PCR (DNMT1 and DNMT3a of PFC and HP). Western blot (DNMT1, reelin and GAD67). Behavioral characterization.	Increased mRNA levels of DNMT1 and DNMT3a (P1 to p60) in the frontal cortex and HP. DNMT overexpression was associated with a decreased in reelin protein expression in frontal cortex. Hyperactivity and impairment of social interaction, prepulse inhibition and fear conditioning, corrected with the administration of valproic acid or clozapine.	Clozapine, Valproic acid	↓ reelin expression in frontal cortex. ↓ reelin promoter methylation
		Palacios-García et al., 2015	Rat	Male and female	E20, P60	open field, elevated plus maze, passive avoidance, Morris water maze (P60)	Rat offspring exposed to PRS (2 h, 1 time per day).	Immunohistochemistry (reelin and NeuN). Cell count of reelin- and NeuN-immunoreactive neurons. Western blot (reelin, Dab1, CDK5, PHF-1 and tubuline). Behavior characterization.	Decreased density of reelin- positive cells in cortex. Decreased reelin protein and gene expression. 79% decrease in reelin immunoreactivity in prefrontal cortex. Increased DNA methylation levels of Reelin promoter. Increased Dab1 adapter protein and decreased phosphorylation of H1 histone. Excessive spontaneous locomotor activity, high anxiety levels and impaired learning and memory consolidation.		↓ reelin positives cells in cortex. ↓ reelin expression. ↑ reelin promoter methylation
		Dong et al., 2016	Mouse	Male	P75	open field, three-chamber (P75)	Mouse offspring exposed to PRS (45 min, 3 times per day, from E7 to E21) treated with clozapine (5 mg/kg, twice a day for 5 days).	Behavior characterization. RT-qPCR (Nse, NeuN). Western blot (DNMT1). Methylated DNA immunoprecipitation.	Clozapine and valproic acid, but not haloperidol, correct the behavioral impairments in PRS mice. Clozapine and valproic acid, but not haloperidol, hypermethylation of psychiatric disorder-related genes. Clozapine treatment corrected the elevated DNMT1 protein expression level and reduced the DNMT1 binding to reelin promoter.	Clozapine, Valproic acid	↓ reelin expression in frontal cortex. ↑ reelin promoter methylation

PRS, prenatal restraint stress.