期刊
NEUROPHARMACOLOGY
卷 112, 期 -, 页码 275-285出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2016.03.001
关键词
Kynurenic acid; Schizophrenia; Cognition; Alpha 7 nicotinic receptor; Choline
资金
- NIH P50 [MH103222]
- NIH [K12 HD43489-14]
- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT [K12HD043489] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF MENTAL HEALTH [P50MH103222] Funding Source: NIH RePORTER
The kynurenine pathway (KP) of tryptophan degradation contains several neuroactive metabolites that may influence brain function in health and disease. Mounting focus has been dedicated to investigating the role of these metabolites during neurodevelopment and elucidating their involvement in the pathophysiology of psychiatric disorders with a developmental component, such as schizophrenia. In this review, we describe the changes in KP metabolism in the brain from gestation until adulthood and illustrate how environmental and genetic factors affect the KP during development. With a particular focus on kynurenic acid, the antagonist of alpha 7 nicotinic acetylcholine (alpha 7nACh) and N-methyl-o-aspartate (NMDA) receptors, both implicated in modulating brain development, we review animal models designed to ascertain the role of perinatal KP elevation on long-lasting biochemical, neuropathological, and behavioral deficits later in life. We present new data demonstrating that combining perinatal choline-supplementation, to potentially increase activation of alpha 7nACh receptors during development, with embryonic kynurenine manipulation is effective in attenuating cognitive impairments in adult rat offspring. With these findings in mind, we conclude the review by discussing the advancement of therapeutic interventions that would target not only symptoms, but potentially the root cause of central nervous system diseases that manifest from a perinatal KP insult. This article is part of the Special Issue entitled 'The Kynurenine Pathway in Health and Disease'. (C) 2016 Elsevier Ltd. All rights reserved.
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