Abstract
N-methyl-D-aspartate (NMDA) receptors play a crucial role in Glutamate (l-Glu) neurotoxicity. To evaluate the effects of astrocyte-derived tryptophan metabolite kynurenic acid (KYNA), on l-Glu neurotoxicity, adult male rats were pretreated with Kynurenine (KYN) which is a precursor of KYNA, at a dose of 30 mg or 300 mg/kg bw i.p., 2 h before stereotactic l-Glu bolus (1μmole/1 μl) administration in cerebral cortex. Results showed that acute l-Glu increased reactive oxygen species, rate of lipid peroxidation, calcium, nitric oxide and neuroinflammatory markers viz. TNF-α, IFN-γ levels and decreased key antioxidant parameters such as SOD, catalase, total glutathione and glutathione reductase along with mitochondrial membrane potential. While peripheral loading of 30 mg/kg dose of KYN had no protective effects on l-Glu induced neurotoxicity, 300 mg/kg dose prevented the above toxic effects following intracortical l-Glu. KYN apparently crossed blood brain barrier to elevate astrocytic-KYNA level, which seems to protect neurons through several interactive mechanisms.
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We acknowledge the council of scientific and industrial research for financial support to AK in the form of a senior research fellowship.
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Kumar, A., Nagesh Babu, G. In Vivo Neuroprotective Effects of Peripheral Kynurenine on Acute Neurotoxicity Induced by Glutamate in Rat Cerebral Cortex. Neurochem Res 35, 636–644 (2010). https://doi.org/10.1007/s11064-009-0114-6
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DOI: https://doi.org/10.1007/s11064-009-0114-6