It has been hypothesized that oxidative imbalance and alterations in nitrergic signaling play a role in the neurobiology of schizophrenia. Preliminary evidence suggests that adjunctive minocycline treatment is efficacious for cognitive and negative symptoms of schizophrenia. This study investigated the effects of minocycline in the prevention and reversal of ketamine-induced schizophrenia-like behaviors in mice. In the reversal protocol, animals received ketamine (20 mg/kg per day intraperitoneally or saline for 14 days, and minocycline (25 or 50 mg/kg daily), risperidone or vehicle treatment from days 8 to 14. In the prevention protocol, mice were pretreated with minocycline, risperidone or vehicle prior to ketamine. Behaviors related to positive (locomotor activity and prepulse inhibition of startle), negative (social interaction) and cognitive (Y maze) symptoms of schizophrenia were also assessed. Glutathione (GSH), thiobarbituric acid-reactive substances (TBARS) and nitrite levels were measured in the prefrontal cortex, hippocampus and striatum. Minocycline and risperidone prevented and reversed ketamine-induced alterations in behavioral paradigms, oxidative markers (i.e. ketamine-induced decrease and increase in GSH levels and TBARS content, respectively) as well as nitrite levels in the striatum. These data provide a rationale for evaluating minocycline as a novel psychotropic agent and suggest that its mechanism of action includes antioxidant and nitrergic systems.

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Studies have suggested that the brain renin angiotensin system (RAS) regulates cerebral flow, autonomic and hormonal systems, stress, innate immune response and behavior, being implicated in several brain disorders such as major depression, Parkinson's and Alzheimer's disease. The angiotensin II receptor subtype 1 (AT1R) is distributed in brain regions responsible for the control of stress response through peripheral and central sympathetic hyperactivation as well as in the hypothalamic paraventricular region, areas known for the release of several neurotransmitters related to inflammatory response facilitation. This relationship leads to the assumption that AT1R might be the receptor most related to the central deleterious actions of angiotensin II. New evidences from clinical studies have shown a possible role for RAS in the pathogenesis of bipolar disorder (BD), a multifactorial disorder with acknowledged presence of neuronal damage via oxidative stress in brain areas such as hippocampus, prefrontal cortex and striatum. Given the studies highlighting AT1R activation as a central pro-inflammatory pathway and, conversely, the involvement of inflammatory response in the pathogenesis of BD; this paper hypothesizes the use of AT1R antagonists for BD management and prevention of its neuroprogression, due to their anti-inflammatory and neuroprotective effects.

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Introduction: Schizophrenia is a serious mental disorder, either because of their symptoms or by its prevalence. This disorder is characterized by the deterioration in cognitive patterns and personality, as well as by the presence of delusions, hallucinations, social isolation, and paranoia. One of the characteristic processes of the pathophysiology of this disorder has only been recently reported named microglial activation in brain areas involved in schizophrenia. Objectives: To show the process of microglial activation in the striatal area of adolescent and adult rats subjected to a schizophrenia model induced by neonatal Poly I: C administration. Methods: Wistar rats were used for the administration of Poly I: C in the 5-7 postnatal days. Microglial activation assessment was performed in the following lifespan periods: 35 days old (teen animals), 60 days old (young animals), and 74 days old (Adult animals) rats. Experimental rats had their brains removed, processed, fixed and mounted on saline slides. The histological sections were processed for antigen retrieval, and immunofluorescence was performed according to the laboratory protocol standard. Brain sections were incubated with polyclonal rabbit antibody anti-Iba1 (MNK 4428, Wako Pure Chemicals, Neuss, Germany). Results: In the striatum of adult rats exposed to Poly I: C, Iba-1 immunofluorescence (microglia marker) showed decreased percentage of cell ramifications and increased cell body of microglial cells, representing a high microglial activation compared to control adult rats. In teen animals treated with Poly I: C, this activation was mild to moderate, when compared to control teen animals, while the animals treated with clozapine showed reduced microglial activation in adulthood. Conclusions:The results show a high activation of microglial cells in the striatum of adult animals submitted to neonatal immune challenge with poly I: C. We have also shown the ability of clozapine to reverse the percentage of expression of microglial activation.