title: Maternal separation prior to neonatal hypoxia-ischemia: Impact on emotional aspects of behavior and markers of synaptic plasticity in hippocampus.
abstract: Exposure to early-life stress is associated with long-term alterations in brain and behavior, and may aggravate the outcome of neurological insults. This study aimed at investigating the possible interaction between maternal separation, a model of early stress, and subsequent neonatal hypoxia-ischemia on emotional behavior and markers of synaptic plasticity in hippocampus. Therefore, rat pups (N=60) were maternally separated for a prolonged (MS 180min) or a brief (MS 15min) period during the first six postnatal days, while a control group was left undisturbed. Hypoxia-ischemia was applied to a subgroup of each rearing condition on postnatal day 7. Emotional behavior was examined at three months of age and included assessments of anxiety (elevated plus maze), depression-like behavior (forced swimming) and spontaneous exploration (open field). Synaptic plasticity was evaluated based on BDNF and synaptophysin expression in CA3 and dentate gyrus hippocampal regions. We found that neonatal hypoxia-ischemia caused increased levels of anxiety, depression-like behavior and locomotor activity (ambulation). Higher anxiety levels were also seen in maternally separated rats (MS180min) compared to non-maternally separated rats, but prolonged maternal separation prior to HI did not potentiate the HI-associated effect. No differences among the three rearing conditions were found regarding depression-like behavior or ambulation. Immunohistochemical evaluation of synaptophysin revealed that both prolonged maternal separation (MS180min) and neonatal hypoxia-ischemia significantly reduced its expression in the CA3 and dentate gyrus. Decreases in synaptophysin expression in these areas were not exacerbated in rats that were maternally separated for a prolonged period prior to HI. Regarding BDNF expression, we found a significant decrease in immunoreactivity only in the hypoxic-ischemic rats that were subjected to the prolonged maternal separation paradigm. The above findings suggest that early-life stress prior to neonatal hypoxia-ischemia leads to significant alterations in synaptic plasticity of the dorsal hippocampus during adulthood, but does not exacerbate HI-related changes in emotional behavior.
authors.affiliation: Laboratory of Cognitive Neuroscience, School of Psychology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Markostamou
authors.affiliation: Laboratory of Cognitive Neuroscience, School of Psychology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Anestis
authors.initials: A
authors.lastname: Ioannidis
authors.affiliation: Laboratory of Cognitive Neuroscience, School of Psychology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Evgenia
authors.initials: E
authors.lastname: Dandi
authors.affiliation: Laboratory of Cognitive Neuroscience, School of Psychology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Maria-Aikaterini
authors.initials: MA
authors.lastname: Mandyla
authors.affiliation: Laboratory of Experimental Neurology & Neuroimmunology, B' Department of Neurology, AHEPA University Hospital, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Evangelia
authors.initials: E
authors.lastname: Nousiopoulou
authors.affiliation: Laboratory of Experimental Physiology, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Constantina
authors.initials: C
authors.lastname: Simeonidou
authors.affiliation: Laboratory of Experimental Physiology, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece. Electronic address: spandou@med.auth.gr.
authors.forename: Evangelia
authors.initials: E
authors.lastname: Spandou
authors.affiliation: Laboratory of Cognitive Neuroscience, 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
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology*; D000860:Hypoxia / Q000150:complications*; D008297:Male; D008426:Maternal Deprivation; D018782:Maze Learning / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013315:Stress, Psychological / Q000209:etiology* / Q000473:pathology*; D013550:Swimming / Q000523:psychology; D016708:Synaptophysin / Q000378:metabolism; D013997:Time Factors
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D016708:Synaptophysin
keywords: Anxiety; BDFN; Depression-like behavior; Neonatal hypoxia-ischemia; Neonatal stress; Synaptophysin