Investigation of the Effect of Nicotinamide Riboside on Cognitive Functions in a Rat Model of Schizophrenia Induced by Ketamine

Project no. 32205 · Status: Kapanmış (Yayın bekleniyor) · 2024

Summary

Schizophrenia is a serious health condition that leads to impairments in social and cognitive abilities. Dysfunctions in brain energy metabolism and mitochondrial function are believed to play a role in the pathophysiology of the disorder. Although antipsychotics used in treatment provide partial improvement, they have also been shown to exert detrimental effects on mitochondrial function. This study aimed to evaluate the effects of nicotinamide riboside (NR), a natural precursor of nicotinamide adenine dinucleotide (NAD) which is essential for mitochondrial function, on cognitive performance in a ketamine-induced rat model of schizophrenia.Sixty adult male Sprague-Dawley rats were included in the study. The experimental groups were as follows: Control (C), Schizophrenia model - Ketamine (KET), Nicotinamide Riboside (NR), Ketamine + Nicotinamide Riboside (KETNR), Ketamine + Antipsychotic (KETAP), and Ketamine + Antipsychotic + Nicotinamide Riboside (KETAPNR). Following the completion of injections, all animals were subjected to the locomotor activity test, sucrose preference test, and novel object recognition test. After behavioral assessments, brain tissues were collected for biochemical analyses. Levels of BDNF, GSH, LDH, CATALASE, and CASPASE-3 were measured using ELISA, and brain pH was assessed using a pH meter.In the novel object recognition test, the KETAPNR group demonstrated significantly higher performance compared to the KET, KETNR, and KETAP groups (p < 0.05). In the sucrose preference test, the KETAPNR and NR groups showed significantly lower performance relative to the control group (p < 0.05). In the locomotor activity test, the KETAPNR group exhibited significantly reduced performance compared to the C, KET, and KETAP groups (p < 0.05). Biochemical analyses revealed that LDH levels in the prefrontal cortex (PFC) of the KETAPNR group were significantly lower than those in the KET, KETNR, and KETAP groups.Our findings suggest that the combined administration of NR and antipsychotics may enhance cognitive functions while improving positive symptoms in a ketamine-induced schizophrenia model.

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