Modulation of the effects of lindane on cognitive function and oxidative stress by neurosteroids in rats


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Neurosteroids are recognized as important modulators of functioning of the nervous system. They have been recognized to influence several neurobehavioral processes including memory and cognition. Lindane, an organochlorine pesticide has been shown to adversely affect memory and induce oxidative stress on both acute and chronic exposure. The present study was thus designed to explore the modulation of effects of lindane over cognitive function by progesterone (PROG), pregnenolone sulfate (PREG-S) and 4’-chlorodiazepam (4CD).Male Wistar rats were used for the study. The control groups were administered a) the vehicle in which the drugs were dissolved b) lindane and c) PROG, PREG-S or 4CD alone. The other three groups received PROG, PREG-S or 4CD following pre treatment with lindane for a period of 6 weeks. Cognitive function was assessed using step-down latency (SDL) on a passive avoidance apparatus and transfer latency (TL) on a plus maze weekly starting from one day before beginning of any treatment till the end of study period. Oxidative stress was assessed at the end of the study period by examining brain malondialdehyde (MDA) and reduced glutathione (GSH) levels.1.Control group showed no change in cognitive function during the study period.2.The group treated with lindane showed a decline in cognitive function as measured by increased TL and decreased SDL. This group also showed significant a increase in oxidative stress as witnessed by an increase in brain MDA and decrease in brain GSH levels.3.PROG), PREG-S and 4CD treatment without lindane did not demonstrate any change in cognitive function over the study period. No change in MDA levels were observed as compared to the control group. However, PREG-S and 4CD treatment group demonstrated a significant increase in brain GSH levels while PROG alone treated group did not show any significant change in the brain GSH levels.4.PROG failed to alter the lindane induced changes in TL, SDL, MDA, GSH. 5.PREG-S or 4CD treatment following lindane administration for 6 weeks was able to reverse the cognitive impairment induced by lindane as shown by improvement in SDL. The two drugs also reversed lindane induced oxidative stress as demonstrated by the decreased MDA and increased GSH levels in these groups compared to lindane only treated groups.6.Lindane induced impairment of TL was not modified PREG-S or 4CD treatment.PREG-S and 4CD were able to reverse the lindane induced cognitive impairment at least in the Step down latency paradigm. The two drugs also reversed the derangement in oxidative stress parameters of MDA and GSH produced by lindane. PROG failed to influence memory impairment and oxidative stress induced by lindane. None of the drugs were able to modulate the changes induced by Lindane in the transfer latency paradigm. Our study reveals a possible correlation between memory impairment and oxidative stress in brain signifying yet another potential role of neurosteroids in the functioning of nervous system and possible use of this group of chemicals in reversing the damage induced by toxicants like lindane in the brain.