Neurochemical Research

, Volume 21, Issue 10, pp 1201–1207 | Cite as

Acute neurotoxicity ofl-glutamate induced by impairment of the glutamate uptake system

  • Seiji Okazaki
  • Yoshihiko Nishida
  • Hisaomi Kawai
  • Shiro Saito
Original Articles


We examined the effect of the glutamate uptake inhibitorl-trans-pyrrolidine-2,4-dicarboxylic acid (PDC) on the neurotoxicity ofl-glutamate in organotypic cultures of rat spinal cord. Eighteen-day-old cultures were incubated with 500 μMl-glutamate, 1 mM PDC, or both. After 72 hours, the tissues were stained for acetylcholinesterase (AChE), and the ventral horn AChE-positive neurons (VHANs) analyzed using morphometry. Neitherl-glutamate nor PDC affected AChE staining, but in combination they produced markedly reduced AChE staining in the dorsal horn and a significant decrease in the number of VHANs (especially the smaller VHANs) as compared with the control. Moreover, treatment with 200 μM PDC for 2 weeks preferentially affected the smaller VHANs. The neurotoxicity ofl-glutamate plus PDC was blocked by the N-methyl-d-aspartate (NMDA) antagonist 3-((RS)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP).

Results suggest that glutamate uptake system has an important protective function in the aggravation of acute neuronal damage.

Key Words

l-Glutamate glutamate transport neurotoxicity acetylcholinesterase organotypic explant culture spinal cord 


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Copyright information

© Plenum Publishing Corporation 1996

Authors and Affiliations

  • Seiji Okazaki
    • 1
  • Yoshihiko Nishida
    • 1
  • Hisaomi Kawai
    • 1
  • Shiro Saito
    • 1
  1. 1.The First Department of Internal Medicine, School of MedicineThe University of TokushimaTokushima CityJapan

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