title: Resilience and vulnerability are dose-dependently related to neonatal stressors in mice.
abstract: Early life experiences have been shown to adjust cognitive abilities, stress reactivity, fear responses and immune activity in adult mammals of many species. However, whereas severe stressors have been generally associated with the emergence of hypothalamic pituitary adreno-cortical (HPA)-mediated pathology, mild neonatal stressful experiences have been traditionally associated with 'positive' effects or resilience. External stressors stimulate the HPA axis to induce a corticosterone secretion in mouse dams, which, in turn is directly transmitted to the progeny through lactation. Such corticosteroid transfer may offer a unitary mechanism whereby early low corticosterone exposure may favor resilience in the offspring and high corticosterone increase vulnerability to pathology. In this study we further investigated this hypothesis by evaluating the long-term effects of a neonatal exposure to low (33 mg/l) and high (100 mg/l) doses of corticosterone during the first 10 days of life in outbred CD-1 mice through supplementation in the maternal drinking water. Offspring attentional set-shifting abilities, central neurotrophic regulation and levels of natural auto-antibodies (na-Abs) directed to serotonin (SERT) and dopamine (DAT) transporters were assessed in adulthood. While low levels of neonatal corticosterone improved adult cognitive abilities and increased na-Abs levels directed to SERT, high doses of neonatal corticosterone reduced hippocampal BDNF levels and na-Abs directed to DAT. These findings confirm and extend our previous findings, supporting the view that both adaptive plasticity and pathological outcomes in adulthood may depend on circulating neonatal corticosterone levels and that these effects follow a U-shaped profile.
authors.affiliation: Section of Behavioural Neuroscience, Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, Roma, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Macrì
authors.forename: Oleg
authors.initials: O
authors.lastname: Granstrem
authors.forename: Maria
authors.initials: M
authors.lastname: Shumilina
authors.forename: Fernando João
authors.initials: FJ
authors.lastname: Antunes Gomes dos Santos
authors.forename: Alessandra
authors.initials: A
authors.lastname: Berry
authors.forename: Luciano
authors.initials: L
authors.lastname: Saso
authors.forename: Giovanni
authors.initials: G
authors.lastname: Laviola
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001323:Autoantibodies / Q000097:blood / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000503:physiopathology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003071:Cognition / Q000187:drug effects* / Q000502:physiology; D003345:Corticosterone / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development / Q000503:physiopathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009483:Neuropsychological Tests; D050486:Serotonin Plasma Membrane Transport Proteins / Q000276:immunology; D013315:Stress, Psychological / Q000139:chemically induced* / Q000503:physiopathology; D013997:Time Factors
chemical_list: D001323:Autoantibodies; D019208:Brain-Derived Neurotrophic Factor; D050483:Dopamine Plasma Membrane Transport Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse; D003345:Corticosterone