Long-lasting, reversible and non-neurotoxic inactivation of hippocampus activity induced by neosaxitoxin

Abstract

Background: 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.

New method: 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.

Results: 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.

Comparison with existing methods: Intracerebral NeoSTX injection showed longer effects than other voltage sodium channel blocker, with minimal spreading and no neuronal damage.

Conclusion: 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.

Keywords: Chronic inactivation; Hippocampus; Long-term; Neosaxitoxin; PSP toxins.