A Study on the Alleviating Effects of N-phthaloyl-γ-Aminobutyric Acid (P-GABA) on the Behavioral, Histopathological and Biochemical Adverse Effects of Sleep Deprivation in Zebrafish (Danio rerio)

Abstract

Background: Sleep is defined as a reversible behavioural state of perceptual disconnection from insensitivity to the environment that facilitates the interaction of physiological and behavioural processes. Sleep Deprivation (S.D.) is defined as a decrease in sleeping duration below the recommended minimum, which has been linked to learning and memory problems.
 Aim: The primary objective of this work was to determine the effect of P-GABA on metabolic parameters, behavioural changes, whole-body cortisol, and brain histology in light-induced sleep-deprived zebrafish, as well as the optimal dose of P-GABA neutralizing undesirable effects.
 Methodology: The present study was conducted for ten days, consisting of three days in a row of sleep deprivation and seven days of treatment with P-GABA. The current investigation used six fishes in a group (n=6).
 Group 1: Control ; Group 2: 24h Total SD ; Group 3: 48h Total SD ; Group 4: 72h Total SD ; Group 5: 24h Total SD + P-GABA (100 mg/L) ; Group 6: 48h Total SD + P-GABA (100 mg/L) ;Group 7: 72h Total SD + P-GABA (100 mg/L)
 Results: The current study provides scientific data demonstrating the positive effects of P-GABA in treating sleep deprivation and associated cognitive impairment. To test if P-GABA treatment can alleviate the cognitive and memory impairment caused by S.D., we established non-toxic concentrations and treated the zebrafish with a safe dose of 100mg/L. The use of P-GABA increased cognitive performance in the T-maze, demonstrating that it has a favourable effect in a sleep-deprivation condition. The SD group exhibited neutrophil infiltration, and this S.D fish treated with P-GABA at a concentration of 100 mg/L demonstrated a moderate reduction in neuronal cell degeneration compared to controls. The levels of biochemical parameters during sleep deprivation and treatment phase with P-GABA were checked. It was evident from the results that the SOD, CAT and GPX levels in the S.D groups were drastically decreased, whereas treatment with P-GABA could show a significant increase in the levels of biochemical parameters.
 In contrast to the control group, zebrafish subjected to sleep deprivation showed enhanced AChE activity in the brain. The results of the P-GABA indicated an anti-AChE profile, which corresponds to improved memory parameters in zebrafish, as observed in the NTT and T-maze tests. When comparing the sleep-deprived fish to the control group, the MDA level, which indicates lipid peroxidation, was higher. Treatment with P-GABA considerably reduced the amount of MDA produced compared to the amount produced in sleep-deprived fish. The cortisol levels gradually increased in the single row 24h, 48h, and 72h sleep deprived groups. There was a gradual decrease in cortisol levels in the groups that received P-GABA treatment. The levels of neurotransmitters were seen to be decreased in the sleep-deprived groups when compared with the control. Upon treatment with P-GABA, the neurotransmitters were restored to near normal.
 Conclusion: This study showed that P-GABA counteracts cognitive performance decrease and anxiety increase resulting from sleep deprivation through a mechanism implying mitigation of brain oxidative stress and regulation of AChE activity.