KISSPEPTIN SYSTEM MODULATES NEUROINFLAMMATION AND BEHAVIOURAL IMPAIRMENTS IN TEMPORAL LOBE EPILEPSY

Temporal lobe epilepsy (TLE), the most prevalent drug-resistant form, involves a neuroinflammatory cascade where hormones and inflammatory mediators interact. Kisspeptin, a neurohormone, increases hippocampal synaptic transmission, yet its involvement in epilepsy remains unclear. Hence, this study was designed to elucidate the spatial expression and role of kisspeptin system in a rat model of TLE. The expression profile of kisspeptin, its receptor and key neuroinflammatory molecules were evaluated in the hippocampus, anterior temporal lobe (ATL), and neocortex at transcript and protein levels under the epileptic conditions. Further, correlations between neuroinflammation and Kiss1/Kiss1r expression, and the cellular distribution of Kiss1r relative to microglial (Iba1), astrocytic (Gfap), and neuronal (NeuN) markers were assessed under TLE conditions. Exogenous Kisspeptin-10 (Kp-10) was injected intraperitoneally to the TLE rats, followed by histological analysis, qPCR, ELISA, and novel object recognition (NOR) behavioural test. Expression of Kiss1, Kiss1r, and key neuroinflammatory markers were altered across hippocampal, ATL, and neocortical regions in TLE. Chronic epileptic neuroinflammation downregulated Kiss1/Kiss1r transcripts that showed region-specific alteration at protein levels. Kiss1r co-localised with Iba1, Gfap and NeuN markers. Kp-10 administration upregulated IL-10 in hippocampus and ATL, and downregulated IL-1β in hippocampus of TLE rats. The NOR test revealed enhanced memory discrimination in Kp-10-treated TLE rats along with improved survival. These findings demonstrated that persistent neuroinflammation impairs kisspeptin signalling, exacerbating TLE pathology. Conversely, Kp-10 holds potential to attenuate inflammation, restore cognitive function, and promote survival, highlighting its possible neuroprotective role in TLE.