Characterization of the kynurenine pathway in human oligodendrocytes

Lim, Chai K.; Smythe, George A.; Stocker, Roland; Brew, Bruce J.; Guillemin, Gilles J.

doi:10.1016/j.ics.2007.07.011

Cited by 30 publications

(44 citation statements)

References 14 publications

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“…We have previously shown that in vitro IDO-1 is expressed in human primary neurons, astrocytes and microglia upon IFN-γ stimulation [34] but that it is missing in the oligodendrocyte [35]. In human AD hippocampus, IDO-1 is expressed in astrocytes and microglia and to a lesser extent in neurons [14].…”

Section: Discussionmentioning

confidence: 99%

Expression of Tryptophan 2,3-Dioxygenase and Production of Kynurenine Pathway Metabolites in Triple Transgenic Mice and Human Alzheimer's Disease Brain

et al. 2013

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To assess the role of the kynurenine pathway in the pathology of Alzheimer's disease (AD), the expression and localization of key components of the kynurenine pathway including the key regulatory enzyme tryptophan 2,3 dioxygenase (TDO), and the metabolites tryptophan, kynurenine, kynurenic acid, quinolinic acid and picolinic acid were assessed in different brain regions of triple transgenic AD mice. The expression and cell distribution of TDO and quinolinic acid, and their co-localization with neurofibrillary tangles and senile β amyloid deposition were also determined in hippocampal sections from human AD brains. The expression of TDO mRNA was significantly increased in the cerebellum of AD mouse brain. Immunohistochemistry demonstrated that the density of TDO immuno-positive cells was significantly higher in the AD mice. The production of the excitotoxin quinolinic acid strongly increased in the hippocampus in a progressive and age-dependent manner in AD mice. Significantly higher TDO and indoleamine 2,3 dioxygenase 1 immunoreactivity was observed in the hippocampus of AD patients. Furthermore, TDO co-localizes with quinolinic acid, neurofibrillary tangles-tau and amyloid deposits in the hippocampus of AD. These results show that the kynurenine pathway is over-activated in AD mice. This is the first report demonstrating that TDO is highly expressed in the brains of AD mice and in AD patients, suggesting that TDO-mediated activation of the kynurenine pathway could be involved in neurofibrillary tangles formation and associated with senile plaque. Our study adds to the evidence that the kynurenine pathway may play important roles in the neurodegenerative processes of AD.

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Section: Discussionmentioning

confidence: 99%

Expression of Tryptophan 2,3-Dioxygenase and Production of Kynurenine Pathway Metabolites in Triple Transgenic Mice and Human Alzheimer's Disease Brain

et al. 2013

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“…In the CNS, the KP is fully expressed in microglia, macrophages and neurons, but only partially in astrocytes and oligodendrocytes (Guillemin et al. 2001, 2003, 2007; Lim et al. 2007).…”

Section: Discussionmentioning

confidence: 99%

Characterization of the kynurenine pathway in NSC‐34 cell line: implications for amyotrophic lateral sclerosis

Chen¹,

Brew²,

Guillemin³

2011

Journal of Neurochemistry

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J. Neurochem. (2011) 118, 816–825. Abstract Amyotrophic lateral sclerosis (ALS) is the most common type of motor neuron degenerative disease for which the aetiology is still unknown. The kynurenine pathway (KP) is a major degradative pathway of tryptophan ultimately leading to the production of NAD+ and is also one of the major regulatory mechanisms of the immune response. The KP is known to be involved in several neuroinflammatory disorders. Among the KP intermediates, quinolinic acid (QUIN) is a potent excitotoxin, while kynurenic acid and picolinic acid are both neuroprotectant. This study aimed to (i) characterize the components of the KP in NSC‐34 cells (a rodent motor neuron cell line) and (ii) assess the effects of QUIN on the same cells. RT‐PCR and immunocytochemistry were used to characterize the KP enzymes, and lactate dehydrogenase (LDH) test was used to assess the effect of QUIN in the absence and presence of NMDA receptor antagonists, kynurenines and 1‐methyl tryptophan. Our data demonstrate that a functional KP is present in NSC‐34 cells. LDH tests showed that (i) QUIN toxicity on NSC‐34 cells increases with time and concentration; (ii) NMDA antagonists, 2‐amino‐5‐phosphonopentanoic acid, MK‐801 and memantine, can partially decrease QUIN toxicity; (iii) kynurenic acid can decrease LDH release in a linear manner, whereas picolinic acid does the same but non‐linearly; and (iv) 1‐methyl tryptophan is effective in decreasing QUIN release by the rodent microglial cell line BV‐2 and thus protects NSC‐34 from cell death. There is currently a lack of effective treatment for ALS and our in vitro results provide a novel therapeutic strategy for ALS patients.

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“…Yang et al, 2013), kynurenic acid is poised to influence OPC development. In addition, as oligodendrocytes are also thought to produce kynurenic acid (C. Lim et al, 2007;Wejksza et al, 2005), the promotion of kynurenine-to-kynurenic acid conversion in the periphery by exercise may prevent potential blocking of communication between OPCs and neurons at non-classical synapses (Q. . Similar results have been noted in studies with adiponectin, suggesting that it may be an effector of exercise that acts in alleviating depression and increasing cell genesis (Yau et al, 2014).…”

Section: Metabolismmentioning

confidence: 99%

Behavioral experiences as drivers of oligodendrocyte lineage dynamics and myelin plasticity

2016

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Many behavioral experiences are known to promote hippocampal neurogenesis. In contrast, the ability of behavioral experiences to influence the production of oligodendrocytes and myelin sheath formation remains relatively unknown. However, several recent studies indicate that voluntary exercise and environmental enrichment can positively influence both oligodendrogenesis and myelination, and that, in contrast, social isolation can negatively influence myelination. In this review we summarize studies addressing the influence of behavioral experiences on oligodendrocyte lineage cells and myelin, and highlight potential mechanisms including experience-dependent neuronal activity, metabolites, and stress effectors, as well as both local and systemic secreted factors. Although more study is required to better understand the underlying mechanisms by which behavioral experiences regulate oligodendrocyte lineage cells, this exciting and newly emerging field has already revealed that oligodendrocytes and their progenitors are highly responsive to behavioral experiences and suggest the existence of a complex network of reciprocal interactions among oligodendrocyte lineage development, behavioral experiences, and brain function. Achieving a better understanding of these relationships may have profound implications for human health, and in particular, for our understanding of changes in brain function that occur in response to experiences. This article is part of the Special Issue entitled 'Oligodendrocytes in Health and Disease'.

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Characterization of the kynurenine pathway in human oligodendrocytes

Cited by 30 publications

References 14 publications

Expression of Tryptophan 2,3-Dioxygenase and Production of Kynurenine Pathway Metabolites in Triple Transgenic Mice and Human Alzheimer's Disease Brain

Expression of Tryptophan 2,3-Dioxygenase and Production of Kynurenine Pathway Metabolites in Triple Transgenic Mice and Human Alzheimer's Disease Brain

Characterization of the kynurenine pathway in NSC‐34 cell line: implications for amyotrophic lateral sclerosis

Behavioral experiences as drivers of oligodendrocyte lineage dynamics and myelin plasticity

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