{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T13:51:17Z","timestamp":1790603477840,"version":"4.1.0"},"reference-count":54,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2021,6,22]],"date-time":"2021-06-22T00:00:00Z","timestamp":1624320000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003711","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["BT\/PR20367\/MED\/122\/22\/2016"],"award-info":[{"award-number":["BT\/PR20367\/MED\/122\/22\/2016"]}],"id":[{"id":"10.13039\/501100003711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003711","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["BT\/MED\/122\/SP24580\/2018"],"award-info":[{"award-number":["BT\/MED\/122\/SP24580\/2018"]}],"id":[{"id":"10.13039\/501100003711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Glutamate receptor\u2010mediated enhanced excitatory neurotransmission is typically associated with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE\u2010HS). Kynurenic acid and quinolinic acid are two important tryptophan\u2013kynurenine pathway metabolites that modulate glutamate receptor activity. This study was designed to test the hypothesis that alteration in metabolism of tryptophan\u2013kynurenine pathway metabolites in the hippocampus of patients with MTLE\u2010HS contributes to abnormal glutamatergic transmission.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Levels of tryptophan\u2013kynurenine pathway metabolites were determined using HPLC and LC\u2013MS\/MS in hippocampal samples from patients with MTLE\u2010HS, compared with autopsy and non\u2010seizure control samples. mRNA and protein expressions of tryptophan\u2013kynurenine pathway enzymes were determined by qPCR and Western blot. Spontaneous glutamatergic activities were recorded from pyramidal neurons in the presence of kynurenine and kynurenic acid, using whole\u2010cell patch clamp.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Levels of kynurenic acid were reduced and quinolinic acid levels were raised in hippocampal samples from MTLE\u2010HS patients, whereas kynurenine levels remained unaltered, compared with levels in non\u2010seizure controls. Spontaneous glutamatergic activity in MTLE\u2010HS hippocampal samples was higher than that in non\u2010seizure controls. Treatment with kynurenine inhibited glutamatergic activity in non\u2010seizure control samples but not in MTLE\u2010HS samples. However, exogenously applied kynurenic acid inhibited glutamatergic activity in both non\u2010seizure control and MTLE\u2010HS hippocampal samples. Also, levels of kynurenine aminotransferase II and its cofactor pyridoxal phosphate were reduced in MTLE\u2010HS samples.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>Our findings indicate that altered metabolism of tryptophan\u2013kynurenine pathway metabolites in hippocampus could contribute to hyperglutamatergic tone in patients with MTLE\u2010HS.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.15534","type":"journal-article","created":{"date-parts":[[2021,5,15]],"date-time":"2021-05-15T00:44:21Z","timestamp":1621039461000},"page":"3959-3976","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Altered hippocampal kynurenine pathway metabolism contributes to hyperexcitability in human mesial temporal lobe epilepsy\u2013hippocampal sclerosis"],"prefix":"10.1111","volume":"178","author":[{"given":"Soumil","family":"Dey","sequence":"first","affiliation":[{"name":"Department of Neurosurgery All India Institute of Medical Sciences  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aparna","family":"Banerjee Dixit","sequence":"additional","affiliation":[{"name":"Dr. B. 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