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Blockade of KAT II ...
Blockade of KAT II Facilitates LTP in Kynurenine 3-Monooxygenase Depleted Mice
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- Imbeault, S. (author)
- Karolinska Institutet
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Olive, M. G. (author)
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- Jungholm, O. (author)
- Karolinska Institutet
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- Erhardt, S. (author)
- Karolinska Institutet
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- Wigström, Holger, 1946 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology
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- Engberg, G. (author)
- Karolinska Institutet
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- Jardemark, K. (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2021-08-30
- 2021
- English.
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In: International Journal of Tryptophan Research. - : SAGE Publications. - 1178-6469. ; 14
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Abstract
Subject headings
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- Excess of brain kynurenic acid (KYNA), a neuroactive metabolite of the kynurenine pathway, is known to elicit cognitive dysfunction. In the present study, we investigated spatial working memory in mice with elevated levels of KYNA, induced by targeted deletion of kynurenine 3-monooxygenase (KMO), as well as long-term potentiation (LTP) of field excitatory postsynaptic potentials (fEPSPs) in hippocampal brain slices from these mice. The KMO knock-out (KMO-/-) mice performed more poorly in the spatial working memory task as compared to their wild-type (WT) counterparts, as reflected by fewer correct choices in a T-maze. Both fEPSPs, or LTP, did not significantly differ between the 2 mouse strains. However, administration of PF-04859989, a kynurenine aminotransferase (KAT) II inhibitor, limiting the production of KYNA, facilitated fEPSP and enhanced LTP to a greater extent in hippocampal slices from KMO-/- mice compared to WT mice. The results of the present study point to an essential role for KYNA in modulating LTP in the hippocampus of KMO-/- mice which may account for their dysfunctional spatial working memory.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- Kynurenine
- hippocampus
- electrophysiology
- long-term potentiation
- spatial memory
- spatial working-memory
- d-aspartate receptors
- cerebrospinal-fluid
- pathway-metabolism
- elevated levels
- hippocampal plasticity
- glycine
- site
- acid
- brain
- activation
- Neurosciences & Neurology
Publication and Content Type
- ref (subject category)
- art (subject category)
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