Differential Levels of Tryptophan-Kynurenine Pathway Metabolites in the Hippocampus, Anterior Temporal Lobe, and Neocortex in an Animal Model of Temporal Lobe Epilepsy

被引：6
作者：
Dey, Soumil [1 ]
Dubey, Vivek [2 ]
Dixit, Aparna Banerjee [3 ]
Tripathi, Manjari [4 ]
Chandra, Poodipedi Sarat [1 ]
Banerjee, Jyotirmoy [2 ]
机构：
[1] All India Inst Med Sci, Dept Neurosurg, New Delhi 110029, India
[2] All India Inst Med Sci, Dept Biophys, New Delhi 110029, India
[3] Univ Delhi, Dr BR Ambedkar Ctr Biomed Res, Delhi 110007, India
[4] All India Inst Med Sci, Dept Neurol, New Delhi 110029, India
来源：
CELLS | 2022年 / 11卷 / 22期
关键词：
temporal lobe epilepsy; tryptophan-kynurenine pathway; glutamate receptors; kynurenic acid; patch-clamp technique; NMDA RECEPTORS; ACID; GLUTAMATE; PILOCARPINE; SEIZURE; CORTEX; BRAIN; HPLC;
D O I：
10.3390/cells11223560
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
Glutamate-receptor-mediated hyperexcitability contributes to seizure generation in temporal lobe epilepsy (TLE). Tryptophan-kynurenine pathway (TKP) metabolites regulate glutamate receptor activity under physiological conditions. This study was designed to investigate alterations in the levels of TKP metabolites and the differential regulation of glutamatergic activity by TKP metabolites in the hippocampus, anterior temporal lobe (ATL), and neocortex samples of a lithium-pilocarpine rat model of TLE. We observed that levels of tryptophan were reduced in the hippocampus and ATL samples but unaltered in the neocortex samples. The levels of kynurenic acid were reduced in the hippocampus samples and unaltered in the ATL and neocortex samples of the TLE rats. The levels of kynurenine were unaltered in all three regions of the TLE rats. The magnitude of reduction in these metabolites in all regions was unaltered in the TLE rats. The frequency and amplitude of spontaneous excitatory postsynaptic currents were enhanced in hippocampus ATL samples but not in the neocortex samples of the TLE rats. The exogenous application of kynurenic acid inhibited glutamatergic activity in the slice preparations of all these regions in both the control and the TLE rats. However, the magnitude of reduction in the frequency of kynurenic acid was higher in the hippocampus (18.44 +/- 2.6% in control vs. 30.02 +/- 1.5 in TLE rats) and ATL (16.31 +/- 0.91% in control vs. 29.82 +/- 3.08% in TLE rats) samples of the TLE rats. These findings suggest the differential regulation of glutamatergic activity by TKP metabolites in the hippocampus, ATL, and neocortex of TLE rats.
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页数：11
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