Botulinum neurotoxin E (BoNT/E) reduces CA1 neuron loss and granule cell dispersion, with no effects on chronic seizures, in a mouse model of temporal lobe epilepsy.

Abstract

Mesial temporal lobe epilepsy (MTLE) is often the result of an early insult that induces a reorganization in hippocampal circuitry leading, after a latent period, to chronic epilepsy. Hippocampal rearrangements during the latent phase include neuronal loss, axonal and dendritic plasticity, neurogenesis, and cell repositioning, but the role of these changes in epilepsy development is unclear. Here we have tested whether administration of the synaptic blocker botulinum neurotoxin E (BoNT/E) interferes with development of spontaneous seizures and histopathological changes following an episode of status epilepticus (SE). SE was induced by unilateral intrahippocampal injection of kainic acid in mice and BoNT/E was delivered to the same hippocampus 3 h later. We found that treatment with BoNT/E prolonged the duration of the latent period but did not block the occurrence of spontaneous seizures. At the histopathological level, BoNT/E reduced loss of CA1 pyramidal neurons and dispersion of dentate granule cells. Downregulation of reelin expression along the hippocampal fissure was also suppressed by BoNT/E treatment. Our findings indicate that administration of BoNT/E after SE inhibits specific morphological changes in hippocampal circuitry but not the development of spontaneous seizures. This indicates a dissociation between certain anatomical modifications and establishment of chronic epilepsy in MTLE.

• Authors: Flavia Antonucci, Angelo Di Garbo, Elena Novelli, Ilaria Manno, Ferdinando Sartucci, Yuri Bozzi, Matteo Caleo
• Journal: Experimental neurology (Exp Neurol) Vol. 210 Issue 2 Pg. 388-401 (Apr 2008) ISSN: 0014-4886 [Print] United States
• PMID: 18177862 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Dyskinesia Agents
• Neuropeptide Y
• Reelin Protein
• Reln protein, rat
• Snap25 protein, rat
• Synaptosomal-Associated Protein 25
• Reln protein, mouse
• Botulinum Toxins
• Kainic Acid
• botulinum toxin type E

Topics

• Action Potentials (drug effects)
• Animals
• Anti-Dyskinesia Agents (administration & dosage)
• Botulinum Toxins (administration & dosage)
• Cell Count (methods)
• Disease Models, Animal
• Drug Interactions
• Epilepsy, Temporal Lobe (chemically induced, drug therapy, pathology)
• Gene Expression Regulation (drug effects)
• Hippocampus (pathology)
• Kainic Acid
• Male
• Mice
• Mice, Inbred C57BL
• Neural Inhibition (drug effects)
• Neurons (drug effects)
• Neuropeptide Y (metabolism)
• Reelin Protein
• Synaptosomal-Associated Protein 25 (metabolism)