Effect of Epilepsy and Sleep Deprivation on PLC - B1Receptor Gene Expression in Brain Stem and Behavioural Changes in Rats

Abstract

Epilepsy is one of the most common disorders of the central nervous system characterized by recurrent seizures unprovoked by an acute systemic or neurologic insult. One of every ten people will have at least one epileptic seizure during a normal lifespan, and a third of these will develop epilepsy. Evidences show that epilepsy can disrupt sleep as well as sleep deprivation can increase susceptibility for seizures. Epilepsy was induced in adult Wistar male rat with a single intraperitonial dose of pilocarpine, which is known one of the best models for temporal lobe epilepsy. Rats were partially sleep deprived by modified float over water method. The rats were kept awake for 10 hours daily during their sleep cycle by stand over water method. I investigated the change in feed intake and water consumption in experimental group of rats and alterations in general behaviors in epileptic and sleep of epileptic rats due to sleep deprivation. The pineal gland secrets melatonin into the bloodstream where it modulates the brain stem circuit which plays a key role in influencing the sleep-wake cycle and activate MT1 receptors which then activates PLC-PKC signaling pathway. My last objective was to evaluate the effect of sleep deprivation and epilepsy on PLCß 1 gene expression. A good quality total RNA was isolated which was used for C-DNA preparation but I could not get the amplified product of PLCß 1 gene. The open field test is a good indicator of general exploratory activity which provides simultaneous measures of locomotion, exploration and anxiety. A significant decrease in the exploratory activity in the open field was observed in Control sleep deprived (p<0.001), Epileptic (p<0.001) and Epileptic sleep deprived (p<0.001) showed that epileptic sleep deprived rats show high level of anxiety and depression as compare to epileptic and control sleep deprived, while sleep deprivation in control rats can make their situation worse. “Splash Test” is the indirect measure of body care efficiency. A significant decrease in the number of grooming bouts and increase in duration of grooming was observed in Control sleep deprived (p<0.001), Epileptic (p<0.001) and Epileptic sleep deprived (p<0.001) which can be interpreted as a stress induced attenuation. It has been hypothesized that sleep deprivation represents an oxidative challenge for the brain and that sleep may have a protective role against oxidative damage. Cellular oxidative damage (i.e. Lipid peroxidation) by Peroxidative damage to lipids was determined by measuring Malondialdehyde concentration in Brain Stem, Liver and Kidney by performing Thio Barbituric Acid Reactive Substance enzyme assay spectrophotometrically at 532 nm. Lipid peroxidation was significantly enhanced in Control sleep deprived (p<0.001), Epileptic (p<0.001) and Epileptic sleep deprived (p<0.001) groups When compared to Control. The increase of reactive oxygen species levels can be because of neurochemical alterations during seizures in epileptic groups. The increased lipid peroxidation in sleep deprived groups indicates that inadequate sleep may activate pathway for reactive oxygen formation ultimately causing changes in membrane permeability. Key words: Brain Stem, Epilepsy, Sleep Deprivation, Thio Barbituric Acid Reactive Substance.