Activation of medial septum cholinergic neurons restores cognitive function in temporal lobe epilepsy

Cognitive impairment is the most common complication in patients with temporal lobe epilepsy with hippocampal scle rosis.There is no effective treatment for cognitive impairment.Medial septum cholinergic neurons have been reported to be a potential target for controlling epileptic seizures in tempo ral lobe epile psy.However,their role in the cognitive impairment of temporal lobe epilepsy remains unclear.In this study,we found that patients with temporal lobe epile psy with hippocampal sclerosis had a low memory quotient and severe impairment in verbal memory,but had no impairment in nonverbal memory.The cognitive impairment was slightly correlated with reduced medial septum volume and medial septum-hippocampus tra cts measured by diffusion tensor imaging.In a mouse model of chronic temporal lobe epilepsy induced by kainic acid,the number of medial septum choline rgic neurons was reduced and acetylcholine release was reduced in the hippocampus.Furthermore,selective apoptosis of medial septum cholinergic neurons mimicked the cognitive deficits in epileptic mice,and activation of medial septum cholinergic neurons enhanced hippocampal acetylcholine release and restored cognitive function in both kainic acid-and kindling-induced epile psy models.These res ults suggest that activation of medial septum cholinergic neurons reduces cognitive deficits in temporal lobe epilepsy by increasing acetylcholine release via projections to the hippocampus.

GABAergic Interneuron Cell Therapy for Drug-Resistant Epilepsy

Epilepsy,one of the most common central nervous system disorders,affects about 70 million people of all ages worldwide[1].It is characterized by hyperactive neuronal networks,resulting from imbalanced excitatory and inhibitory activity.Despite the development of multiple next-generation anti-seizure medicines,one-third of epilepsy patients are still drug-resistant[2].

Reactive glia-to-GABAergic neuron reprogramming:a“golden touch”strategy to alleviate intractable seizures

This commentary highlights a research article published recently in Cell Stem Cell“Reprogramming reactive glia into interneurons reduces chronic seizure activity in a mouse model of mesial temporal lobe epilepsy”.Generally,Lentini et al.reveal a strategy to fulfill in vivo glia-to-neuron reprogramming,which is a potential disease-modifying strategy for treatment of intractable seizures.Here,we describe exciting research advances in the treatment of intractable seizures based on this research article,summarizing its key findings,emphasizing its importance and providing further discussions.Further,issues worthy of further investigations are also postulated so that clinic translation can be better achieved.