Syntabulin regulates neuronal excitation/inhibition balance and epileptic seizures by transporting syntaxin 1B

Abstract

Epilepsy is a widespread neurological disorder affecting more than 65 million people, but the mechanisms of epilepsy remains unknown. Abnormal synaptic transmission has a crucial role in the occurrence and development of epilepsy. Here, we found that syntabulin, a neuronal transporter, was mainly localized in neurons, and its expression was increased in epileptic tissues. Knockdown of syntabulin increased susceptibility and severity of epilepsy, whereas overexpression of syntabulin had the opposite effect. Mechanistically, in the epileptic brain tissue, syntabulin mainly translocated syntaxin 1B (STX1B) rather than syntaxin 1A (STX1A) to the presynaptic membrane, which resulted in increased presynaptic transmitter release. Further studies showed that syntabulin had a more significant effect on presynaptic functionality of GABAergic activity over that of excitatory synapses and resulted in an excitation/inhibition (E/I) imbalance, thereby regulating the epileptic phenotype. In addition, we found that the increased expression of syntabulin in epileptic brain tissue was mainly regulated by transcription factor TFAP2A. In summary, syntabulin plays a protective role in epilepsy by maintaining a proper E/I balance in the hippocampus.

Transcriptome and metabolome sequencing identifies glutamate and LPAR1 as potential factors of anlotinib resistance in thyroid cancer

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Genetic deletion of zinc transporter ZnT3 induces progressive cognitive deficits in mice by impairing dendritic spine plasticity and glucose metabolism

“…The synaptosome proteins in the whole brain of mice were obtained using MinuteTM Synaptosome Isolation Kit (SY-052, Invent Biotechnologies, Minnesota, USA), according to the manufacturer's instructions (Ke et al, 2023 ). Briefly, filter cartridges were pre-chilled on ice; brain tissue samples (20–30 mg) were transferred into the cartridges and 200 μl of ice-cold buffer A added.…”

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