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

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Abstract

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.

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Authors and Affiliations

  1. The First Department of Internal Medicine, School of Medicine, The University of Tokushima, Kuramoto 3-18, 770, Tokushima City, Japan

    Seiji Okazaki, Yoshihiko Nishida, Hisaomi Kawai & Shiro Saito

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  1. Seiji Okazaki
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  2. Yoshihiko Nishida
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  3. Hisaomi Kawai
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  4. Shiro Saito
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Okazaki, S., Nishida, Y., Kawai, H. et al. Acute neurotoxicity ofl-glutamate induced by impairment of the glutamate uptake system. Neurochem Res 21, 1201–1207 (1996). https://doi.org/10.1007/BF02532396

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