title: Effects of maternal separation on behavior and brain damage in adult rats exposed to neonatal hypoxia-ischemia.
abstract: Animal studies suggest that maternal separation, a widely used paradigm to study the effects of early life adversity, exerts a profound and life-long impact on both brain and behavior. The aim of the current study was to investigate whether adverse early life experiences interact with neonatal hypoxia-ischemia, affecting the outcome of this neurological insult at both functional and structural levels during adulthood. Rat pups were separated from their mothers during postnatal days 1-6, for either a short (15 min) or prolonged (180 min) period, while another group was left undisturbed. On postnatal day 7, a subgroup from each of the three postnatal manipulations was exposed to a hypoxic-ischemic episode. Behavioral examination took place approximately at three months of age and included tests of learning and memory (Morris water maze, novel object and novel place recognition), as well as motor coordination (rota-rod). We found that both prolonged maternal separation and neonatal hypoxia-ischemia impaired the animals' spatial learning and reference memory. Deficits in spatial but not visual recognition memory were detected only in hypoxic-ischemic rats. Interestingly, prolonged maternal separation prior to neonatal hypoxia-ischemia augmented the reference memory impairments. Histological analysis of infarct size, hippocampal area and thickness of corpus callosum did not reveal any exacerbation of damage in hypoxic-ischemic rats that were maternally separated for a prolonged period. These are the first data suggesting that an adverse postnatal environmental manipulation of just 6 days causes long-term effects on spatial learning and memory and may render the organism more vulnerable to a subsequent insult.
authors.affiliation: School of Psychology, Aristotle University of Thessaloniki, Thessaloniki, Greece. Electronic address: dtata@psy.auth.gr.
authors.forename: Despina A
authors.initials: DA
authors.lastname: Tata
authors.affiliation: School of Psychology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Markostamou
authors.affiliation: School of Psychology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Anestis
authors.initials: A
authors.lastname: Ioannidis
authors.affiliation: School of Psychology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Mara
authors.initials: M
authors.lastname: Gkioka
authors.affiliation: Laboratory of Experimental Physiology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Constantina
authors.initials: C
authors.lastname: Simeonidou
authors.affiliation: Laboratory of Experimental Physiology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Georgios
authors.initials: G
authors.lastname: Anogianakis
authors.affiliation: Laboratory of Experimental Physiology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece. Electronic address: spandou@med.auth.gr.
authors.forename: Evangelia
authors.initials: E
authors.lastname: Spandou
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000254:growth & development / Q000473:pathology* / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D020925:Hypoxia-Ischemia, Brain / Q000150:complications / Q000473:pathology* / Q000503:physiopathology* / Q000523:psychology; D008297:Male; D008426:Maternal Deprivation; D008569:Memory Disorders / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D008570:Memory, Short-Term / Q000502:physiology; D009483:Neuropsychological Tests; D011597:Psychomotor Performance / Q000502:physiology; D011897:Random Allocation; D017208:Rats, Wistar; D021641:Recognition, Psychology / Q000502:physiology; D045442:Rotarod Performance Test; D065853:Spatial Learning / Q000502:physiology; D065852:Spatial Memory / Q000502:physiology; D013315:Stress, Psychological / Q000473:pathology / Q000503:physiopathology; D014796:Visual Perception / Q000502:physiology
keywords: Hippocampus; Infarct; Neonatal hypoxia–ischemia; Neonatal stress; Recognition memory; Spatial learning and memory