Skip to main content
Login | Suomeksi | På svenska | In English

Browsing by Subject "K+ - Cl- co-transporter (KCC2)"

Sort by: Order: Results:

  • Wakade, Anushka (2023)
    Temporal lobe epilepsy (TLE), a condition defined by unprovoked and recurrent seizures originating from the temporal lobe, is among the most ubiquitous of the various forms of epilepsy. Despite being chronic and highly prevalent, the available treatment options concerning the same remains a critical issue. Since the current therapeutic condition of epilepsy requires more development, renewed focus studying its molecular mechanisms and therapies is imminent. One of the longstanding theories trying to decode the molecular perturbations in TLE has been deficits in GABAergic inhibition resulting in abnormal neuronal activation. K+ - Cl- co-transporter (KCC2) activity is vital for maintaining a hyperpolarizing GABA response. The past decades have intimately and causally linked the prognosis of the seizures observed in TLE with deficits in KCC2 functioning. However, the precise mechanisms relevant to the disruption of KCC2 activity are still blurry. Here we show how KCC2 de-stabilization/localization in the neuronal bilayer is a characteristic of epileptic animal tissue. With the help of co-immunoprecipitation assays, western blot, and mass spectrometry, we found that in normal healthy brain tissue, GM1 ganglioside present in the membrane has specific and direct interactions with the KCC2 cotransporter. However, in the pilocarpine model of TLE, the interaction of this complex was significantly disturbed, primarily in the hippocampus and to some extent in the cortex. Our results act as an extension to previous research which stated that the structural association of the KCC2 clusters with neuronal lipid rafts is crucial for the functionality of the KCC2 cotransporter. Having learned about the unique nature of the pathophysiology of TLE, it is imminent to note that additional research in the direction of studying its biochemical pathways is required. The findings of this experimental study support the claim that KCC2 and GM1 as a complex are closely associated in the epileptic conditions and hence, this research paves the way to further explore the role of KCC2 and GM1 as a consequential complex in the pathophysiology of TLE.