Effects of tetanus toxin on synaptic proteins in models of temporal lobe epilepsy

Foss, Lucy Jane (2013). Effects of tetanus toxin on synaptic proteins in models of temporal lobe epilepsy. University of Birmingham. Ph.D.

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Abstract

Injection of tetanus toxin (TeNT), systemically or directly into the brain, has long been known to cause spastic paralysis or seizures respectively: thought to be due to disruption of inhibitory neurons and cleavage of vesicle associated membrane protein 2 (VAMP2). Here we investigate mechanisms involved in TeNT-induced chronic epilepsy in the first 16 days following injections in vivo and focally onto organotypic hippocampal slice cultures. Immunohistochemical analysis identified a spatial and temporal cleavage of both VAMP1 and VAMP2 progressing from day 2 post injection through to days 8 and 16. This was concentration dependent in slice cultures. VAMP1 has been shown to co-localise predominantly with inhibitory and VAMP2 with excitatory neurons. Contradicting previous results we have shown cleavage of both VAMP1 and VAMP2, disruption of both inhibition and excitation and direct effects of the toxin in the contralateral hippocampus. This indicates that inhibitory neurons and VAMP2 are not specifically targeted by TeNT. This project benefits from the combination of electrophysiological and immunohistochemical techniques to uncover functional changes induced by TeNT. It is also the first study of focally injected TeNT onto slice cultures and offers benefits for future long term studies of the effects of the toxin and drug screening.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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