RÉSUMÉ
BACKGROUND: Heightened levels of inflammation and oxidative stress are thought to be involved in the pathophysiology of schizophrenia. We aimed to assess whether intake of anti-inflammatory and anti-oxidant drugs during pregnancy prevents later schizophrenia-related outcomes in a neurodevelopmental rat model of this disorder. METHODS: Pregnant Wistar rats were injected with polyriboinosinic-polyribocytidilic acid (Poly I:C) or saline and subsequently treated with either N-acetyl cysteine (NAC) or omega-3 polyunsaturated fatty acids (PUFAs) until delivery. Controls rats received no treatment. In the offspring, neuroinflammation and anti-oxidant enzyme activity were assessed on postnatal day (PND) 21, 33, 48, and 90. Behavioral testing was performed at PND 90, followed by post-mortem neurochemical assessment and ex vivo MRI. RESULTS: The supplement treatment led to a quicker restoration of the wellbeing of dams. In the adolescent Poly I:C offspring, the supplement treatment prevented an increase in microglial activity and partially prevented a deregulation in the anti-oxidant defense system. In the adult Poly I:C offspring, supplement treatment partially prevented dopamine deficits, which was paralleled by some changes in behavior. Exposure to omega-3 PUFAs prevented the enlargement of lateral ventricles. CONCLUSION: Intake of over-the-counter supplements may assist in especially targeting the inflammatory response related to schizophrenia pathophysiology, aiding in diminishing later disease severity in the offspring.
RÉSUMÉ
We here show that social rank, as assessed by competition for a running wheel, influences ocular dominance plasticity in adult male mice. Dominant animals showed a clear ocular dominance shift after 4 days of MD, whereas their submissive cagemates did not. NMDA receptor activation, reduced GABA inhibition, and serotonin transmission were necessary for this plasticity, but not sufficient to explain the difference between dominant and submissive animals. In contrast, prefrontal dopamine concentration was higher in dominant than submissive mice, and systemic manipulation of dopamine transmission bidirectionally changed ocular dominance plasticity. Thus, we could show that a social hierarchical relationship influences ocular dominance plasticity in the visual cortex via higher-order cortices, most likely the medial prefrontal cortex. Further studies will be needed to elucidate the precise mechanisms by which this regulation takes place.