Abstract
Recently, the implication of oxidative stress in behavioral-like disorders has received a lot of attention. Many studies were interested in searching for new natural compounds with protective effects on behavioral-like disorders by focusing on oxidative stress as the main causal factor. Here, we assess the potential effect of cell-free extracts from halophilic bacteria on memory, anxiety, and depression-related behaviors in mice, as well as on cognitive deficits, negative symptoms, and some oxidative stress biomarkers in methionine-induced mice models of schizophrenia. Firstly, crude extracts of bacteria isolated from the Dead Sea were screened for their effects on memory and anxiety- and depression-like behaviors through Y-maze, elevated plus maze, and forced swimming test, respectively, using two doses 60 mg/kg and 120 mg/kg. Then, 120 mg/kg of two bacterial crude extracts, from two strains designated SL22 and BM20 and identified as Bacillus stratosphericus and Pseudomonas zhaodongensis, respectively, with significant contents of phenolic and flavonoid-like compounds, were selected for the assessment of cognitive and negative symptom improvement, as well as for their effects on oxidative stress status in methionine-induced mice models of schizophrenia using six groups (controls, methionine, crude extracts solely, and combinations of crude extracts and methionine). Results showed that the administration of the crude extracts caused a significant increase in the spontaneous alternations in the Y-maze task, the time spent in open arms of the elevated plus maze, and a decrease in immobility time in the forced swimming test in comparison with the control group. Furthermore, the administration of bacterial extracts seemed to diminish disorders related to cognitive and negative symptoms of schizophrenia and to improve the oxidative state in the temporal lobes, in comparison with the methionine group. Our findings suggest substantial antioxidant and anti-neuropsychiatric effects of the crude extracts prepared from Pseudomonas zhaodongensis strain BM20 and Bacillus stratosphericus strain SL22 and that further studies are needed to purify and to determine the active fraction from the extracts.
Highlights
During the last decade, a great attention was given to the role of oxidative stress in neuropsychiatric disorders
To protect the living systems from reactive oxygen species (ROS) damage and toxicity, various enzymatic and nonenzymatic antioxidant pathways are involved to keep their production under tight control [8]. e protective enzymatic pathways act in a cooperative cascade that includes, among others, superoxide dismutase (SOD) and glutathione peroxidase (GPx) [3, 9] in order to reduce the damaging effect of ROS throughout different processes including prevention of ROS formation, scavenging free radicals, preventing the radical chain reaction of oxidation, and/or retarding the lipid peroxidation process [10]
Considering the pharmaceutical importance of metabolites produced by halophilic bacteria in harsh conditions and their powerful antioxidant activity and in view of the little data reported on the effects of these halophilic bacterial extracts on neuropsychiatric disorders [42], the present study aims at isolating halophilic bacteria producing metabolites that could potentially act on short-term memory impairment, anxiety, depression-like behaviors, and schizophrenia-like disorders in animal models
Summary
A great attention was given to the role of oxidative stress in neuropsychiatric disorders. Erefore, developing novel antipsychotic drugs with better safety and efficacy is crucial In this field, some studies have focused on seeking new natural compounds from medicinal plants with promising value in the treatment of neuropsychiatric disorders [31,32,33], but studies assessing bacterial metabolites for their therapeutic effects as neuropsychiatric behaviors modulating agents remain relatively limited [34,35,36]. Considering the pharmaceutical importance of metabolites produced by halophilic bacteria in harsh conditions and their powerful antioxidant activity and in view of the little data reported on the effects of these halophilic bacterial extracts on neuropsychiatric disorders [42], the present study aims at isolating halophilic bacteria producing metabolites that could potentially act on short-term memory impairment, anxiety, depression-like behaviors, and schizophrenia-like disorders in animal models.
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