Ascorbic acid supplementation attenuates schizophrenia-like symptoms in an animal model induced by ketamine.

Schizophrenia is a chronic neuropsychiatric disorder with a poorly understood pathophysiology. The theories about the disorder are mainly about dysregulation in one or more systems of neurotransmitters, and the progression triggers the presence of inflammatory markers indicates the possibility that the disorder is initially an inflammatory disease. The objective was to evaluate the ascorbic acid supplementation in an animal model of schizophrenia, on behavioral parameters, and cytokines involved in inflammation IL-1ß, IL-10. Wistar rats with 60 days of age were used which were supplemented with ascorbic acid at 0.1, 1, and 10 mg/kg or saline for 14 days via orogastric gavage. Subsequently, four groups were given ketamine (25 mg/kg) and four groups received intraperitoneal saline from the 9th-15th day of the experiment. After 30 min of the last administration of ketamine/saline, and behavioral test, rats were killed by guillotine decapitation and the brain structures were carefully dissected for biochemical analysis. Results showed that ascorbic acid supplementation prevented motor sensory loss but nor alter other parameters evaluated. We concluded that ascorbic acid may be used as a therapeutic adjuvant in schizophrenia and may help to improve the schizophrenic patient's life quality.

Molecular effects of lithium are partially mimicked by inositol-monophosphatase (IMPA)1 knockout mice in a brain region-dependent manner.

We have previously shown that homozygote knockout (KO) of inositol-monophosphatase1 (IMPA1) results in lithium (Li)-like behavior. We now aimed to find out whether Li-treated mice and IMPA1 KO mice exhibit neurochemical similarity at the gene- and protein-expression level. Hippocampal and frontal cortex B-cell lymphoma (Bcl-2), Bcl-2-associated X protein (BAX), P53, Perodoxin2 (PRDX2), myristoylated alanine-rich C kinase substrate (MARCKS) and neuropeptide Y (NPY) mRNA levels, and hippocampal, frontal cortex and hypothalamic cytokine levels, all previously reported to be affected by lithium treatment, were measured in three groups of mice: wildtype (WT) on regular-food (RF), WT on Li-supplemented food (Li-treated) and IMPA1-KOs. Hippocampal and frontal cortex Bcl-2 and MARCKS were the only genes commonly affected (downregulated) by Li and IMPA1 KO; Bcl-2 - by 28% and 19%, respectively; MARCKS - by about 20% in both regions. The effect of Li and of IMPA1 KO on cytokine levels differed among the three brain areas studied. Only in the hippocampus both interventions exerted similar effects. Frontal cortex cytokine levels were unaffected neither by Li nor by IMPA1 KO. Similar changes in Bcl-2 and MARCKS but not in PRDX2 and NPY following both Li-treatment and IMPA1 KO suggest a mechanism different than inositol-monophosphatase1 inhibition for Li׳s effect on the latter genes. The cytokine levels results suggest that the mechanism mediating Li׳s effect on the inflammatory system differs among brain regions. Only in the hippocampus the results favor the involvement of the phosphatidylinositol (PI) cycle.