Table 3.

Major Outcomes Provoked by the Limited Bedding/Nesting paradigm of Chronic Early-Life Stress (ELS) in Mice

ELS Period (PND)	Sex	Strain	Acute/Long Term	Outcomes	References
Stress system perturbations
2–9	Both	C57BL/6J	PND 9 and 4–8 months	Elevated basal corticosterone concentrations.	Rice et al. (2008)
2–9	Both	C57BL/6J	PND9,21,28. and 120	Reduced body weight at PND9,21 Increased CORT at PND120 in males, reduced in females	Arp et al. (2016)
4–11	Male	C57BL/6N	PND8,12,16, 21,28,38,50, and 75	Elevated Corticosterone at PND16, Diminished brain MR and GR at PND12	Bath et al. (2016)
Cognitive and emotional functions
2–9	Both	C57BL/6J	PND 21, 29 and 63	Enhanced anxiety-like behaviors in the novelty-induced hypophagia paradigm.	Malter Cohen et al. (2013)
2–9	Male	129S2/Sv × C57BL/6J	3 months	Enhanced anxiety-like behaviors in OF and light-dark box tests.	Wang et al. (2012)
2–9	Male	C57BL/6J	4–8 months	Memory impairments in MWM and NOR tests No anxiety-like behavior in OF test.	Rice et al. (2008)
2–9	Male	129S2/Sv × C57BL/6J	6 months	Memory impairments in MWM and Y-maze tests.	Wang et al. (2011)
2–9	Both	C57BL/6J	3–4 months	No recognition of ‘safe’ periods after fear learning; impaired spatial memory in males	Arp et al. (2016), Kanatsou et al. (2017)
4–11	Both	C57BL/6N	PND21,28 38,50 and 75	Memory impairment across development in males Memory impairment at PND21 and PND38 in females	Bath et al. (2017)
4–11	Male	C57BL/6N	PND8,12,16 21,28,38,50 and 75	Accelerated development of contextual fear inhibition	Bath et al. (2016)
Brain changes
2–9	Both	C57BL/6J	PND 9	Reduced CRH mRNA expression in the PVN.	Rice et al. (2008)
2–9	Both	C57BL/6J × 129Sv-SvJ	PND 18–26	Upregulation of CRH expression in the PVN Astrocytic glutamate reuptake impairments and enhanced glutamatergic drive onto dorsal-medial neurons of the hypothalamus.	Gunn et al. (2013)
2–9	Both	C57BL/6J × 129Sv-SvJ	8 weeks	Upregulation of CRH expression in the PVN.	Gunn et al. (2013)
2–9	Male	129S2/Sv × C57BL/6J	3 months	No change in the gene expression of CRH and arginine vasopressin in the PVN, MR and GR in the hippocampus and CRH in the central amygdala.	Wang et al. (2012)
2–9	Male	C57BL/6J	4–8 months	Reduced CRH mRNA expression in the PVN.	Rice et al. (2008)
2–9	Male	129S2/Sv × C57BL/6J	6 months	LTP deficits in CA3 Reduced number of dendritic spines in CA3 Reduced inhibitory synaptic density in CA1 and excitatory synaptic density in CA1 and CA3 Reduced Neurexin-1 mRNA levels in CA3 and Neuroligin-3 mRNA levels in CA1.	Wang et al. (2011)
4–11	Male	C57BL/6N	PND8,12,16 21,28,38,50 and 75	Precocious development of PV+ and MBP mRNA, shift in ratio of NR2a:NR2b mRNA in the hippocampus. Earlier decline in Ki-67 and DCX mRNA.	Bath et al. (2016)
2–9	Both	C57BL/6J	PND9	Increased neurogenesis in hippocampus (Ki67, Calretinin)	Naninck et al. (2015)
2–9	Male	C57BL/6J	4 months	Reduced neurogenesis (survival of adult born neurons)	Naninck et al. (2015)
2–9	Male	C57BL/6J	PND9 and 4 months	Altered microglia (Iba1 and CD68) and cytokine expression in hippocampus	Hoeijmakers et al. (2016)
2–9	Male	C57BL/6J/APP/PS1	4 months 10 months	Reduced cell associated amyloid pathology Reduced amyloid plaques	Lesuis et al. (2016) Hoeijmakers et al. (2016)
Metabolic changes
2–9	Both	C57BL/6J	PND 9 and 4 months	Reduced white adipose tissue (WAT) mass and reduced leptin (mRNA in WAT as well as circulating)	Yam et al. (2017)
2–9	Male	C57BL/6J	PND9	Altered methionine in plasma and brain	Naninck et al. (2016)

CORT, corticosterone; CRH, corticotropin releasing hormone; DCX, doublecortin; GR, glucocorticoid receptor; LTP, long-term potentiation; MBP, myelin basic protein; MR, mineralocorticoid receptor; MWM, Morris water maze; NOR, novel object recognition; NR, NMDA receptor subunit; OF, open field; PND, postnatal day; PV+, parvalbumin positive; PVN, paraventricular nucleus of hypothalamus

Based on: Molet et al. Dev Psychobiol 2014 with updates