Picolinic acid blocks the neurotoxic but not the neuroexcitant properties of quinolinic acid in the rat brain: Evidence from turning behaviour and tyrosine hydroxylase immunohistochemistry

Beninger, Richard J.; Colton, Adrianne; Ingles, Janet L.; Jhamandas, K; Boegman, R.J.

doi:10.1016/0306-4522(94)90438-3

Cited by 72 publications

(51 citation statements)

References 19 publications

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“…At higher concentrations, it acts at the glutamate site of the NMDA receptor (29). PIC also contributes to brain homeostasis by similarly blocking the neurotoxic effects of QUIN (30). However, it has been suggested that the constitutive synthesis of PIC is overwhelmed by de novo QUIN production during neuroinflammation (31).…”

Section: Involvement Of the Kp In Neurotoxicitymentioning

confidence: 99%

The Kynurenine Pathway in Brain Tumor Pathogenesis

et al. 2012

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Brain tumors are among the most common and most chemoresistant tumors. Despite treatment with aggressive treatment strategies, the prognosis for patients harboring malignant gliomas remains dismal. The kynurenine pathway (KP) is the principal route of L-tryptophan catabolism leading to the formation of the essential pyridine nucleotide, nicotinamide adenine dinucleotide (NAD þ ), and important neuroactive metabolites, including the neurotoxin, quinolinic acid (QUIN), the neuroprotective agent, picolinic acid (PIC), the T H 17/Treg balance modulator, 3-hydroxyanthranilic acid (3-HAA), and the immunosuppressive agent, L-Kynurenine (KYN). This review provides a new perspective on KP dysregulation in defeating antitumor immune responses, specifically bringing light to the lower segment of the KP, particularly QUIN-induced neurotoxicity and downregulation of the enzyme a-amino-b-carboxymuconate-e-semialdehyde decarboxylase (ACMSD) as a potential mechanism of tumor progression. Given its immunosuppressive effects, 3-HAA produced from the KP may also play a role in suppressing antitumor immunity in human tumors. The enzyme indoleamine 2, 3-dioxygenase (IDO-1) initiates and regulates the first step of the KP in most cells. Mounting evidence directly implicates that the induction and overexpression of IDO-1 in various tumors is a crucial mechanism facilitating tumor immune evasion and persistence. Tryptophan 2, 3-dioxygenase (TDO-2), which initiates the same first step of the KP as IDO-1, has likewise recently been shown to be a mechanism of tumoral immune resistance. Further, it was also recently shown that TDO-2-dependent production of KYN by brain tumors might be a novel mechanism for suppressing antitumor immunity and supporting tumor growth through the activation of the Aryl hydrocarbon receptor (AhR). This newly identified TDO-2-KYN-AhR signaling pathway opens up exciting future research opportunities and may represent a novel therapeutic target in cancer therapy. Our discussion points to a number of KP components, namely TDO-2, IDO-1, and ACMSD, as important therapeutic targets for the treatment of brain cancer. Targeting the KP in brain tumors may represent a viable strategy likely to prevent QUIN-induced neurotoxicity and KYN and 3-HAA-mediated immune suppression. Cancer Res; 72(22); 5649-57. Ó2012 AACR.

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Section: Involvement Of the Kp In Neurotoxicitymentioning

confidence: 99%

The Kynurenine Pathway in Brain Tumor Pathogenesis

et al. 2012

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“…Lim et al [40] found no significant differences in KA levels between children with newly diagnosed ASD in 15 different Omani families and their age-matched healthy siblings ( n = 12). However, the ASD children exhibited significant lower levels of picolinic acid, which has well-described neuroprotective functions [41], while the QA level was significantly higher in the ASD patients than in the control group. We found no significant differences in QA level between the present ASD group and the healthy controls.…”

Section: Discussionmentioning

confidence: 99%

Kynurenine Pathway in Autism Spectrum Disorders in Children

et al. 2017

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Background: There is increasing evidence that altered immune responses play a role in the pathogenesis of autism spectrum disorders (ASD), together with dysfunction of the serotonergic and glutamatergic systems. Since the kynurenine (KYN) pathway that degrades tryptophan (TRP) is activated in various neuroinflammatory states, we aimed to determine whether this pathway is activated in ASD. Methods: Sixty-five pediatric ASD patients (including 52 boys) were enrolled from an epidemiological survey covering 2 counties in Norway; 30 (46.5%) of these patients were diagnosed with childhood autism, 16 (24.6%) with Asperger syndrome, 12 (18.5%) with atypical autism, 1 (1.5%) with Rett syndrome, and 6 (9.2%) with other ASD. The serum levels of the following markers were measured in the children with ASD and compared to those in 30 healthy children: TRP, KYN, kynurenic acid (KA), 3-hydroxykynurenine, and quinolinic acid. Results: The mean serum level of KA was significantly lower in the ASD group than in the healthy controls (28.97 vs. 34.44 nM, p = 0.040), while the KYN/KA ratio was significantly higher in the ASD group (61.12 vs. 50.39, p = 0.006). The same relative values were found when comparing the childhood autism subgroup with the controls. Also, the mean serum level of TRP was significantly lower in children with a subdiagnosis of childhood autism than in those with Asperger syndrome (67.26 vs. 77.79 μM, p = 0.020). Conclusion: Our study indicates that there is an increased neurotoxic potential and also a possible lower KYN aminotransferase activity in ASD.

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“…Picolinic acid, a naturally occurring catabolite of tryptophan metabolism, has been shown to be neuroprotective against the toxic effects of quinolinic acid, an excitotoxic tryptophan metabolite [30]. Its ability to function as a protective immunomodulator has been demonstrated in several studies involving intracerebral infection and tumor growth [31,32].…”

Section: Introductionmentioning

confidence: 99%

Effects of Pre- and Postnatal Exposure to Chromium Picolinate or Picolinic Acid on Neurological Development in CD-1 Mice

Bailey

Boohaker

Jernigan

et al. 2008

Biol Trace Elem Res

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Chromium picolinate, Cr(pic)3, a popular dietary supplement marketed as an aid in fat loss and lean muscle gain, has also been suggested as a therapy for women with gestational diabetes. The current study investigated the effects of maternal exposure to Cr(pic)3 and picolinic acid during gestation and lactation on neurological development of the offspring. Mated female CD-1 mice were fed diets from implantation through weaning that were either untreated or that contained Cr(pic)3 (200 mg kg(-1) day(-1)) or picolinic acid (174 mg kg(-1) day(-1)). A comprehensive battery of postnatal tests was administered, including a modified Fox battery, straight-channel swim, open-field activity, and odor-discrimination tests. Pups exposed to picolinic acid tended to weigh less than either control or Cr(pic)3-exposed pups, although the differences were not significant. Offspring of picolinic acid-treated dams also appeared to display impaired learning ability, diminished olfactory orientation ability, and decreased forelimb grip strength, although the differences among the treatment groups were not significant. The results indicate that there were no significant effects on the offspring with regard to neurological development from supplementation of the dams with either Cr(pic)3 or picolinic acid.

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Picolinic acid blocks the neurotoxic but not the neuroexcitant properties of quinolinic acid in the rat brain: Evidence from turning behaviour and tyrosine hydroxylase immunohistochemistry

Cited by 72 publications

References 19 publications

The Kynurenine Pathway in Brain Tumor Pathogenesis

The Kynurenine Pathway in Brain Tumor Pathogenesis

Kynurenine Pathway in Autism Spectrum Disorders in Children

Effects of Pre- and Postnatal Exposure to Chromium Picolinate or Picolinic Acid on Neurological Development in CD-1 Mice

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