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Infect Immun, June 1998, p. 2501-2508, Vol. 66, No. 6
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Neurotoxicity of Clostridium perfringens Epsilon-Toxin for the Rat Hippocampus via the Glutamatergic System

Osamu Miyamoto,1 Junzaburo Minami,2 Tetsuhiko Toyoshima,1 Takehiro Nakamura,3 Tetsuya Masada,3 Seigo Nagao,3 Tetsuro Negi,4 Toshifumi Itano,1 and Akinobu Okabe2,*

Departments of Biology,1 Microbiology,2 Neurosurgery,3 and Basic Sports Medicine,4 Kagawa Medical University, Ikenobe, Kagawa 761-0793, Japan

Received 22 December 1997/Returned for modification 6 February 1998/Accepted 5 March 1998

The neurotoxicity of epsilon-toxin, one of the major lethal toxins produced by Clostridium perfringens type B, was studied by histological examination of the rat brain. When the toxin was injected intravenously at a lethal dose (100 ng/kg), neuronal damage was observed in many areas of the brain. Injection of the toxin at a sublethal dose (50 ng/kg) caused neuronal damage predominantly in the hippocampus: pyramidal cells in the hippocampus showed marked shrinkage and karyopyknosis, or so-called dark cells. The dark cells lost the immunoreactivity to microtubule-associated protein-2, a postsynaptic somal and dendric marker, while acetylcholinesterase-positive fibers were not affected. Timm's zinc staining revealed that zinc ions were depleted in the mossy layers of the CA3 subfield containing glutamate as a synaptic transmitter. The cerebral blood flow in the hippocampus was not altered significantly before or after administration of the toxin, as measured by laser-Doppler flowmetry, excluding the possibility that the observed histological change was due to a secondary effect of ischemia in the hippocampus. Prior injection of either a glutamate release inhibitor or a glutamate receptor antagonist protected the hippocampus from the neuronal damage caused by epsilon-toxin. These results suggest that epsilon-toxin acts on the glutamatergic system and evokes excessive release of glutamate, leading to neuronal damage.

* Corresponding author. Mailing address: Department of Microbiology, Kagawa Medical University, 1750-1, Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan. Phone and fax: 81-87-891-2129. E-mail: microbio{at}kms.ac.jp.

Infect Immun, June 1998, p. 2501-2508, Vol. 66, No. 6
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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