The influence of quercetin on recognition memory and brain oxidative damage in a ketamine model of schizophrenia

Abstract

OBJECTIVE: The aims of this study were to investigate the protective effect of quercetin on changes in recognition memory as assessed by the novel object recognition (NOR) test, as well as on changes in the oxidative stress levels in the hippocampus and prefrontal cortex, produced in a model of memory impairment in schizophrenia induced by administration of a subanesthetic dose of ketamine. METHODS: A total of 40 Balb-C mice were randomly divided into five groups (Corn oil + Saline, Quercetin 50 + Saline, Corn oil + Ketamine, Quercetin 25 + Ketamine, Quercetin 50 + Ketamine). Corn oil and Quercetin (25 or 50 mg/kg/day) was given by orogastric gavage once daily for 21 days. Corn oil was chosen as the vehicle and administered at the same volume as quercetin. Ketamine was injected at a dose of 25 mg/kg intraperitoneally (i.p.) for a period of 7 days starting from the 15th day. Behavioural responses were evaluated with the NOR test. The activity levels of antioxidant enzymes and levels of malondialdehyde (MDA) were assayed in the prefrontal cortex and hippocampus. RESULTS: The time of exploration of the novel object was longer than T F (time to explore the familiar object) in the Corn oil + Saline and Quercetin 50 + Saline groups in NOR Test-1 (p < .05). The discrimination ratios of the Quercetin 50 + Ketamine and Corn oil + Ketamine groups were significantly lower than that of the Quercetin 50 + Saline group (p < .05). The discrimination ratios of the Quercetin 50 + Ketamine and Corn oil + Saline groups were significantly lower than that of the Quercetin 50 + Saline group (p < .05). The time of exploration of the novel object was longer than T F in the Corn oil + Saline and Quercetin 50 + Ketamine groups in NOR Test-2 (p < .05). The discrimination ratios of the Corn oil + Ketamine and Quercetin 25 + Ketamine groups were significantly lower than those of the Quercetin 50 + Ketamine group (p < .05). Quercetin at 50 mg/kg reduced the MDA levels and elevated the SOD and GPx activity compared to the Corn oil + Ketamine group. CONCLUSION: These results show that quercetin has the potential to improve cognitive deficits in mice and that quercetin may be useful for treating the symptoms of schizophrenia, partially due to its ability to scavenge free radicals and its high antioxidant capacity.

Repurposing of Anti-Diabetic Agents as a New Opportunity to Alleviate Cognitive Impairment in Neurodegenerative and Neuropsychiatric Disorders

“…Quercetin also improved the chronic unpredicted stress-mediated memory dysfunction through normalizing metabolic aberration, attenuating insulin resistance, elevating hippocampal GLUT4 levels, and maintaining neuronal integrity( Mehta et al, 2017 ). In a ketamine model of schizophrenia, quercetin showed the potential to improve cognitive deficits, partly owing to its ability to scavenge free radicals and its high antioxidant capacity( Mert et al, 2019 ). However, a clinical study failed to demonstrate the effects of a 12-week quercetin supplementation program on cognitive function( Broman-Fulks et al, 2012 ).…”

Is There a Glutathione Centered Redox Dysregulation Subtype of Schizophrenia?

“…Quercetin [160,161] (NCT04063124), Ethyl eicosopentanoic acid [76,145] Genistein [162,163] (NCT01982578) Glucose-dependent insulionotropic polypeptide [143] Andrographolide [164] Alpha-lipoic acid [144] (NCT03788759) CXA-10 [165] L-arginine [142] (NCT04054973)…”

“…An exciting clinical utility of prospectively identifying patients with GSH-deficit is the therapeutic possibility of correcting it. A number of compounds with the potential to correct the effects of GSH deficit are in the pipeline ( Table 2 ) [ 44 , 76 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 , 152 , 153 , 154 , 155 , 156 , 157 , 158 , 159 , 160 , 161 , 162 , 163 , 164 , 165 , 166 , 167 , 168 , 169 , 170 , 171 ]. Of these, N-acetylcysteine has been shown to improve cognition and negative symptoms (6 RCTs) [ 172 ], though the effect size is modest.…”

Is There a Glutathione Centered Redox Dysregulation Subtype of Schizophrenia?

“…Quercetin [157,158] [NCT04063124], Ethyl eicosopentanoic acid [76,142] Genistein [159,160] [NCT01982578] Glucose-dependent insulionotropic polypeptide [140] Andrographolide [161] Alpha-lipoic acid [141] [NCT03788759] Luteolin [166,167] Trehalose [153] [NCT02800161]…”