title: Maternal separation impairs long term-potentiation in CA1-CA3 synapses and hippocampal-dependent memory in old rats.
abstract: Exposure to chronic stress during the neonatal period is known to induce permanent long-term changes in the central nervous system and hipothalamic-pituitary-adrenal axis reactivity that are associated with increased levels of depression, anxiety, and cognitive impairments. In rodents, a validated model of early life stress is the maternal separation (MS) paradigm, which has been shown to have long-term consequences for the pups that span to adulthood. We hypothesized that the early life stress-associated effects could be exacerbated with aging, because it is often accompanied by cognitive decline. Using a MS model in which rat pups were separated from their mothers for 3 hours daily, during postnatal days 2-14, we evaluated the long-term functional consequences to aged animals (70-week-old), by measuring synaptic plasticity and cognitive performance. The baseline behavioral deficits of aged control rats were further exacerbated in MS animals, indicating that early-life stress induces sustained changes in anxiety-like behavior and hippocampal-dependent memory that are maintained much later in life. We then investigated whether these differences are linked to impaired function of hippocampal neurons by recording hippocampal long-term potentiation from Schaffer collaterals/CA1 synapses. The magnitude of the hippocampal long-term potentiation induced by high-frequency stimulation was significantly lower in aged MS animals than in age-matched controls. These results substantiate the hypothesis that the neuronal and endocrine alterations induced by early-life stress are long lasting, and are able to exacerbate the mild age-associated deficits.
authors.affiliation: Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Lisbon, Portugal; Institute of Pharmacology and Neurosciences, Faculty of Medicine, University of Lisbon, Lisbon, Portugal.
authors.forename: Vasco C
authors.initials: VC
authors.lastname: Sousa
authors.affiliation: Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Lisbon, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Vital
authors.affiliation: Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Lisbon, Portugal.
authors.forename: Ana Rita
authors.initials: AR
authors.lastname: Costenla
authors.affiliation: Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Lisbon, Portugal.
authors.forename: Vânia L
authors.initials: VL
authors.lastname: Batalha
authors.affiliation: Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Lisbon, Portugal; Institute of Pharmacology and Neurosciences, Faculty of Medicine, University of Lisbon, Lisbon, Portugal.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Sebastião
authors.affiliation: Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Lisbon, Portugal; Institute of Pharmacology and Neurosciences, Faculty of Medicine, University of Lisbon, Lisbon, Portugal.
authors.forename: Joaquim A
authors.initials: JA
authors.lastname: Ribeiro
authors.affiliation: Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Lisbon, Portugal. Electronic address: lvlopes@fm.ul.pt.
authors.forename: Luísa V
authors.initials: LV
authors.lastname: Lopes
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001007:Anxiety / Q000503:physiopathology; D001522:Behavior, Animal / Q000502:physiology*; D056547:CA1 Region, Hippocampal / Q000502:physiology*; D056651:CA2 Region, Hippocampal / Q000502:physiology*; D056654:CA3 Region, Hippocampal / Q000502:physiology*; D005260:Female; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D008426:Maternal Deprivation; D008568:Memory / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D013315:Stress, Psychological / Q000503:physiopathology*; D013569:Synapses / Q000502:physiology*
keywords: Aging; Hippocampus; LTP; Maternal separation; Memory; Stress