(783.5) Sleep Disruption Exacerbates Cognitive Dysfunction by Promoting Lipid-Immune Dysregulation in the Corticohippocampal System of Pentylenetetrazol-Kindled Rats

Poster Board Number: C71
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Edem Edem (University of Lagos, University of Lagos), Kate Nebo (Afe Babalola University), Peculiar Rimamchatin (Afe Babalola University), Aisha Bello (Afe Babalola University), Elizabeth Akinluyi (Afe Babalola University), Adedamola Fafure (Afe Babalola University), Olusegun Adeoluwa (Afe Babalola University), Adesina Adekeye (Afe Babalola University), Ademola Oremosu (University of Lagos)

Sleep deprivation has been identified as one of the triggers for seizures in patients with generalised epilepsy. Therefore, we tested whether rapid eye movement (REM) sleep deprivation would increase susceptibility to developing generalised seizures established by pentylenetetrazol (PTZ) kindling; and whether REM sleep deprivation would affect treatment response and cognitive outcomes in epileptic rats. Furthermore, possible mechanistic underpinnings such as lipid-immune responses in the prefrontal cortex and hippocampus were evaluated. Male rats were either sleep-deprived followed by PTZ kindling, or kindled before being sleep-deprived, or kindled before sleep deprivation and treated with a known anticonvulsant, diazepam. Thereafter, cognitive behaviours were evaluated. Following euthanasia, the prefrontal cortex and hippocampus were extracted and processed for biochemical and histological/histochemical/immunohistochemical assessments. Our results showed increased susceptibility to epileptogenesis in the group exposed to sleep deprivation before kindling compared to the PTZ-kindling group without sleep deprivation. Also, sleep deprivation aggravated epilepsy features in the sleep-deprived PTZ-kindled rats and negatively impacted drug (diazepam) response in these animals. These were all linked to a disruption in lipid profile, and interleukin-17 (IL-17) activity; exacerbation in demyelination, microglial activation, and low-density lipoprotein receptor-related protein 1 (LRP1) expression in the prefrontal cortex and hippocampus following sleep deprivation and PTZ kindling. Furthermore, we observed a substantial deterioration in spatial working memory especially in the sleep-deprived PTZ-kindled group compared to the kindled group. Overall, our findings suggest that impairment of cognitive functions as seen in the sleep deprivation before kindling and sleep deprivation after kindling groups is attributable to a perturbation in the interaction between lipoproteins, their receptors, immune cells and their inflammatory/phagocytic responses impairing myelination/remyelination, thus aggravating cognitive deficits.

Keywords: Paradoxical sleep deprivation; Epilepsy; Lipid profile; Low-density lipoprotein receptor-related protein 1; Cognitive impairment.

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