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.

Adolescent raloxifene treatment in females prevents cognitive deficits in a neurodevelopmental rodent model of schizophrenia.

The existence of sex differences in schizophrenia is a well documented phenomenon which led to the hypothesis that female sex hormones are neuroprotective and hence responsible for the more favorable disease characteristics seen in women. The current study sought to investigate the effects of estrogen-like agents administered during early adolescence on behavioral outcomes in adulthood using the neurodevelopmental maternal immune activation (MIA) rodent model of schizophrenia. Female MIA offspring were administered during the asymptomatic period of adolescence with either 17ß-estradiol, raloxifene or saline and were tested in late adolescence and adulthood for schizophrenia-related behavioral performance. We report here that whereas adult female MIA offspring exhibited cognitive deficits in the form of retarded spatial learning, the administration of raloxifene during adolescence was sufficient in preventing these deficits and resulted in intact performance in the MIA group.

Recurrent stress across life may improve cognitive performance in individual rats, suggesting the induction of resilience.

Depressive symptoms are often accompanied by cognitive impairments and recurrent depressive episodes are discussed as a potential risk for dementia. Especially, stressful life events are considered a potent risk factor for depression. Here, we induced recurrent stress-induced depressive episodes over the life span of rats, followed by cognitive assessment in the symptom-free period. Rats exposed to stress-induced depressive episodes learned faster than control rats. A high degree of stress-induced depressive-like behavior early in the paradigm was a predictor of improved cognitive performance, suggesting induction of resilience. Subsequently, exposure to lorazepam prior to stress-induced depressive episodes and cognitive testing in a nonaversive environment prevented the positive effect. This indicates a beneficial effect of the stress-associated situation, with the existence of individual coping abilities. Altogether, stress may in some have a beneficial effect, yet for those individuals unable to tackle these aversive events, consecutive unpleasant episodes may lead to worse cognitive performance later in life.

Learning deficits in rats overexpressing the dopamine transporter.

With its capacity to modulate motor control and motivational as well as cognitive functions dopamine is implicated in numerous neuropsychiatric diseases. The present study investigated whether an imbalance in dopamine homeostasis as evident in the dopamine overexpressing rat model (DAT-tg), results in learning and memory deficits associated with changes in adult hippocampal neurogenesis. Adult DAT-tg and control rats were subjected to the Morris water maze, the radial arm maze and a discrimination reversal paradigm and newly generated neurons in hippocampal circuitry were investigated post mortem. DAT-tg rats were found to exhibit a striking inability to acquire information and deploy spatial search strategies. At the same time, reduced integration of adult-born neurons in hippocampal circuitry was observed, which together with changes in striatal dopamine signalling might explain behavioural deficits.