T-588 protects motor neuron death against glutamate-induced neurotoxicity.
To examine the possible neuroprotective effect of T-588 against glutamate-induced neurotoxicity, we analyzed the pharmacological utility of T-588 in a postnatal organotypic culture model of motor neuron degeneration. Treatment with 10(-5) M of glutamate resulted a motor neuron loss and decreased activity of choline acetyltransferase (ChAT). Cotreatment of 10(-5) M of glutamate and T-588 revealed a protective effect against motor neuron death and decreased ChAT activity. We concluded that T-588 may play important roles in the survival and maintenance of spinal motor neurons in its neuroprotection against glutamate-induced neurotoxicity. Our data may provide a rationale for designing a therapeutic strategy for protection against pathologically induced motor neuron damage or cell death such as amyotrophic lateral sclerosis and motor neuropathy.
Iwasaki
Yasuo
Y
Department of Neurology, Toho University Omori Hospital, Tokyo, Japan. yaso@med.toho-u.ac.jp
Ichikawa
Yasumitsu
Y
Igarasi
Osamu
O
Aoyagi
Joe
J
Konno
Shingo
S
Ikeda
Ken
K
Iguchi
Hiroaki
H
Kawabe
Seiichi
S
Marubuchi
Shigeki
S
Ono
Satoshi
S
D000818:Animals; D016923:Cell Death / Q000187:drug effects*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004048:Diethylamines / Q000494:pharmacology*; D018698:Glutamic Acid / Q000633:toxicity*; D009046:Motor Neurons / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D013876:Thiophenes / Q000494:pharmacology*
D004048:Diethylamines; D013876:Thiophenes; C082372:T 588; D018698:Glutamic Acid; D002795:Choline O-Acetyltransferase