Acetoacetate protects hippocampal neurons against glutamate-mediated neuronal damage during glycolysis inhibition
Section snippets
Animal treatments
Male Wistar rats (250–320 g) were used throughout the study. They were handled according to the Rules for Research in Health Matters (Mexico) and the local animal care committee approved all animal treatments. All efforts were made to minimize the number of animals used and their suffering. For chronic glycolysis inhibition studies animals received a daily i.p. injection of 15 mg/kg iodoacetate (Sigma, St. Louis, MO, USA) dissolved in 10 mM phosphate buffer during 3 days. It has been previously
Results
Administration of the glutamate transport inhibitor PDC (500 nmol/μl) induces small lesions in the CA1 hippocampal region (Fig. 1), which are largely potentiated in animals chronically treated with iodoacetate for 3 days. In these animals intracerebral injection of PDC results in extensive neuronal damage to pyramidal cells of the CA1 region, and lesions 3.1-fold larger than those produced by PDC in intact rats (Fig. 1). Fig. 2 shows brain sections of a representative intact animal
Discussion
In previous studies we have shown that glutamate uptake inhibition by PDC induces important increases in the extracellular concentration of the excitatory amino acids, glutamate and aspartate, probably by the reverse activation of glutamate transporters as suggested by in vitro experiments Izumi et al., 1996, Volterra et al., 1996. These increases produce neuronal damage in the rat hippocampus and striatum in vivo, and in cultured cerebellar granule cells when energy metabolism is impaired
Acknowledgements
This study was supported in part by grants IN203400 PAPIIT, UNAM and 27970-N and 40306-M CONACYT.
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