Studies with botulinum toxins in excitatory and inhibitory neurons

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• 作者：Matteoli Michela ; Grumelli Carlotta ; Verderio Claudia
• 关键词：AP-25 BoNT/A
• 刊名：Toxicon
• 出版年：2008
• 出版时间：1 June 2008
• 年：2008
• 卷：51
• 期：Supplement 1
• 页码：7
• 全文大小：40 K

文摘

Botulinum toxins BoNT/A and BoNT/E, which inhibit neurotransmitter release by cleaving SNAP-25, have been reported to block synaptic vesicle recycling preferentially at excitatory but to much lesser degree at inhibitory synapses (Verderio et al., 2004). This evidence has recently been complemented by the observation that BoNT/A or BoNT/E affect predominantly excitatory with respect to inhibitory neurotransmitter release from rat

synaptosomes (Verderio et al., 2007). To prove that resistance of GABAergic terminals did not depend on differences in toxin receptors, the traffic of the toxins was examined in cultured neurons. The results indicated that BoNT/A and BoNT/E are able to equally enter and translocate into the cytosol in both types of neurons. Interestingly, exogenous expression of SNAP-25 in GABAergic neurons conferred sensitivity to BoNT/A. These results are opened to different interpretations: first, SNAP-25 might substitute a putative, endogenous BoNT-resistant SNARE; second, the 1–197 fragment may act as dominant negative for exocytosis. Also, it has been shown that SNAP-25 negatively modulates calcium responsiveness to depolarization (Pozzi et al., 2008) and that BoNT/A-inhibition can be overcome by high Ca²⁺ concentrations (Capogna et al., 1997). A third possibility, therefore, is that exogenous expression of SNAP-25, by reducing Ca²⁺ responsiveness of GABAergic neurons, may confer sensitivity to BoNT/A. These possibilities are currently under evaluation.