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)
Uthirakumar Devaraj
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Tamilnadu, India.
Tamilarasan Shanmugasundaram
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Tamilnadu, India.
Ammu Ramu
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Tamilnadu, India.
Elumalai Balamurugan *
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Tamilnadu, India.
*Author to whom correspondence should be addressed.
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.
Keywords: Antioxidant, behaviour, cognition, sleep deprivation, zebrafish