Departamento de Neurociencia, Facultad de Medicina, Universidad de Chile, Chile; Biomedical Neuroscience Institute (BNI), Chile.
Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Chile.
J Neurosci Methods. 2018 Oct 1;308:197-204. doi: 10.1016/j.jneumeth.2018.08.013. Epub 2018 Aug 11.
Neosaxitoxin (NeoSTX) and related paralytics shellfish toxins has been successfully used as local anesthetic and muscle relaxants to treat a variety of ailments. The primary mechanism of action of these toxins occurs by blocking voltage-gated sodium channels with compounds such as TTX, lidocaine, or derivatives. However, most of these non-classical sodium channel blockers act with a reduced time effect as well as ensuing neurotoxicity.
In this report, we show that the use of local NeoSTX injections inactivates the hippocampal neuronal activity reversibly with a by long-term dynamics, without neuronal damage.
A single 10 ng/μl injection of NeoSTX in the dorsal CA1 region abolished for up to 48 h memory capacities and neuronal activity measured by the neuronal marker c-fos. After 72 h of toxin injection, the animals fully recover their memory capacities and hippocampal neuronal activity. The histological inspection of NeoSTX injected brain regions revealed no damage to the tissue or reactive gliosis, similar to vehicle injection. Acute electrophysiological recording in vivo shows, also, minimal spreading of the NeoSTX in the cerebral tissue.
Intracerebral NeoSTX injection showed longer effects than other voltage sodium channel blocker, with minimal spreading and no neuronal damage.
NeoSTX is a new useful tool that reversibly inactivates different brains region for a long time, with minimal diffusion and without neuronal damage. Moreover, NeoSTX can be used as a valuable sodium channel blocker for many studies in vivo and with potential therapeutic uses.
neosaxitoxin（NeoSTX）和相关的麻痹性贝类毒素已成功地被用作局部麻醉剂和肌肉松弛剂来治疗各种疾病。这些毒素的主要作用机制是通过与 TTX、利多卡因或其衍生物等化合物结合来阻断电压门控钠离子通道。然而，大多数这些非经典的钠离子通道阻断剂的作用时间较短，且随之而来的神经毒性也较大。
在本报告中，我们表明，局部使用 NeoSTX 注射可在不损伤神经元的情况下，通过长期动力学可逆地使海马神经元活动失活。
在背侧 CA1 区单次注射 10ng/μl 的 NeoSTX 可使记忆能力和神经元活性（通过神经元标志物 c-fos 测量）丧失长达 48 小时。在毒素注射 72 小时后，动物完全恢复了记忆能力和海马神经元活性。对 NeoSTX 注射脑区的组织学检查显示，组织无损伤或无反应性神经胶质增生，与载体注射相似。急性电生理记录显示，NeoSTX 在脑组织中的扩散也很小。
脑内 NeoSTX 注射的效果比其他电压门控钠离子通道阻断剂持续时间更长，扩散最小，无神经元损伤。
NeoSTX 是一种新的有用工具，它可以长时间可逆地使不同的大脑区域失活，扩散最小，且无神经元损伤。此外，NeoSTX 可用作体内许多研究的有价值的钠离子通道阻断剂，具有潜在的治疗用途。
