Neurotoxicity of Clostridium perfringens epsilon-toxin for the rat hippocampus via the glutamatergic system.
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.
Miyamoto
O
O
Departments of Biology, Kagawa Medical University, Ikenobe, Kagawa 761-0793, Japan.
Minami
J
J
Toyoshima
T
T
Nakamura
T
T
Masada
T
T
Nagao
S
S
Negi
T
T
Itano
T
T
Okabe
A
A
D000818:Animals; D001427:Bacterial Toxins / Q000633:toxicity*; D001921:Brain / Q000187:drug effects / Q000473:pathology; D003016:Clostridium perfringens; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D005971:Glutamates / Q000378:metabolism*; D006624:Hippocampus / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D009498:Neurotoxins / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000378:metabolism; D012039:Regional Blood Flow / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects
D001427:Bacterial Toxins; C039811:Clostridium perfringens epsilon-toxin; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates; D009498:Neurotoxins; D017470:Receptors, Glutamate; D016291:Dizocilpine Maleate