(-) Xanthosamide is beneficial to the synaptic transmission of synapses in the hippocampal CA1 region

A team of researchers from the Chinese Academy of Medical Sciences Peking Union Medical College, Chen Naihong, recently published an article in the European Journal of Pharmacology, focusing on the role of (-) ceramide in the hippocampal Schaffer collateral-CA1 synapses.
Xanthosamide is a chemical component proposed from the folk yellow leaves for the treatment of rheumatism and hepatitis. (-) and (+) ceramide are the left-handed and right-handed bodies of the synthesized ceramide. It has been found that (-) ceramide has anti-hypoxia and stimulating effects, can improve memory impairment caused by various causes, and has obvious protection on behavioral and brain histopathology in animal models of learning and memory dysfunction. Improve the role. However, the exact mechanism of the action of the yellow amide has not been solved.
In this study, electrophysiological methods were used to observe and record (-) ceramide in promoting the fast excitatory postsynaptic potential (F-EPSP) in the CA1 region of rat hippocampal slices by MED64 planar microelectrode matrix recording system. The results indicate that (-) ceramide will enhance synaptic transmission at doses of 0.1, 1 and 10 μM. If previously incubated with nimodipine (L-type voltage-dependent calcium channel blocker, 10 μM), this enhancement is completely inhibited, but after the addition of (-) ceramide, nimodipine is added. There is no inhibitory effect at all. However, lanine base (ranine base blocker, 100 μM), whether added to the incubation before or after the (-) flavinamide reaction, affects the slope of F-EPSP. The data indicate that (-) ceramide promotes calcium influx and triggers intracellular calcium release, thereby enhancing synaptic transmission. Intracellular calcium release induced by (-) ceramide at concentrations of 0.1, 1 and 10 μM promoted the activation of CaMKIIα, whereas pretreatment with KN93 (CaMKIIα inhibitor, 10 μM) completely blocked (-) yellow rind Enhancement of amide-induced synaptic transmission. The cAMP response element binding protein was activated by (-) flavinamide and inhibited by KN93, but H89 (PKA inhibitor, 10 μM) did not affect the element, indicating that (-) flavinamide promotes synaptic transmission via the PKA-independent pathway. In summary, (-) ceramide helps promote calcium influx, triggers intracellular calcium release, and then activates the CaMKIIα-CREB signaling pathway to enhance synaptic transmission.

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