الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Psychosis is a complex psychiatric condition associated with positive, negative and cognitive symptoms. Genetic predisposition and exposure to environmental stresses both involved in the pathogenesis of psychosis. Many studies demonstrated that psychosis occurs as a result of neurotransmitters disturbance such as dopamine and glutamate, neuronal oxidative stress, neuroinflammation, neuronal pyroptosis and synaptic loss which in turn makes structural and functional alterations in the brain, specially the PFC and hippocampus. Ketamine induced psychosis animal model proved to mimic the consequences of psychotic like symptoms in humans.
EMPA has shown a powerful antioxidant and anti-inflammatory activity in many research studies. However, the possible neuroprotective effects of EMPA in psychosis remains to be elucidated.
In the present study, fifty rats were divided into five groups; (10 rats each) control group, ketamine induced psychosis untreated group and three treated group, group 3 was treated with EMPA, group 4 was treated with EMPA and risperidone, and group 5 was treated with risperidone alone. Psychosis was performed by intraperitoneal injection (I.P) of ketamine at a dose of (20 mg /kg) once daily for 7 consecutive days. Concerning group 3, it received (10 mg/kg) of EMPA by orally once daily for 14 consecutive days starting from day 8 after induction of the model. As regard group 4, the rats in this group after psychosis induction by ketamine as mentioned in group 2, received EMPA at a dose of (10 mg /kg) orally once daily combined with risperidone at a dose of (1 mg /kg) orally once daily with 30 minutes’ interval between the two drugs for 14 consecutive days starting from 8thday of experiment. Rats in group 5 received I.P injection of ketamine at a dose of (20 mg/kg) once daily for 7 consecutive days followed by risperidone at a dose of (1 mg /kg) orally for 14 consecutive days starting from the 8th day of experiment. At the end of the study, Random blood glucose level was measured and rats were exposed to behavioral assessments by, open filed test, sucrose preference test, forced swim test and novel object recognition test. Then, they were sacrificed for biochemical analysis of the PFC and hippocampus. PFC and hippocampal oxidative stress markers including MDA, GSH, inflammatory markers as IL-1β and caspase-1 levels were also assessed. Histopathological analysis of the PFC and hippocampus was also performed. Immunohistochemistry for NLRP3 inflammasome activation in the microglial cell was also done.
The present work observed that psychosis induced anxiety-like and depressive-like behavior, caused marked oxidative stress, neuroinflammation and pyroptosis compared to the control group. Immunohistochemistry showed numerous brown stained microglial cells indicating activation of NLRP3 inflammosome in psychosis. In addition, histological analysis illustrated disorganized prefrontal cortical and hippocampal architecture with evidence of neuronal loss.
Treatment with EMPA alone improved behavioral, biochemical parameters as well as histological structure. However, the combination of EMPA with risperidone showed the greatest improvement in all studied parameters. Meanwhile, treatment with risperidone alone was the least effective.
Based on the data above, the present study showed that EMPA improved behavioral parameters and preserved the normal histological architecture of the PFC and hippocampus following psychosis, adding on, the reducing effect of EMPA on NLRP3 inflammasome activation in microglial cells. In addition, the antioxidant, anti-inflammatory, anti-apoptotic properties of EMPA are the possible mechanisms for these effects