Supplement Treatment with NAC and Omega-3 Polyunsaturated Fatty Acids during Pregnancy Partially Prevents Schizophrenia-Related Outcomes in the Poly I:C Rat Model.

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.

Presymptomatic Reduction of Individuality in the AppNL-F Knockin Model of Alzheimer's Disease.

BACKGROUND: One-third of the risk for Alzheimer's disease is explained by environment and lifestyle, but Alzheimer's disease pathology might also affect lifestyle and thereby impair the individual potential for health behavior and prevention. METHODS: We examined in mice how the AppNL-F/NL-F (NL-F) knockin mutation affects the presymptomatic response to environmental enrichment (ENR) as an experimental paradigm addressing nongenetic factors. We assessed the emergence of interindividual phenotypic variation under the condition that both the genetic background and the shared environment were held constant, thereby isolating the contribution of individual behavior (nonshared environment). RESULTS: After 4 months of ENR, the mean and variability of plasma ApoE were increased in NL-F mice, suggesting a presymptomatic variation in pathogenic processes. Roaming entropy as a measure of behavioral activity was continuously assessed with radiofrequency identification (RFID) technology and revealed reduced habituation and variance in NL-F mice compared with control animals, which do not carry a Beyreuther/Iberian mutation. Intraindividual variation decreased, while behavioral stability was reduced in NL-F mice. Seven months after discontinuation of ENR, we found no difference in plaque size and number, but ENR increased variance in hippocampal plaque counts in NL-F mice. A reactive increase in adult hippocampal neurogenesis in NL-F mice, known from other models, was normalized by ENR. CONCLUSIONS: Our data suggest that while NL-F has early effects on individual behavioral patterns in response to ENR, there are lasting effects on cellular plasticity even after the discontinuation of ENR. Hence, early behavior matters for maintaining individual behavioral trajectories and brain plasticity even under maximally constrained conditions.