β-adrenergic enhancement of brain kynurenic acid production mediated via cAMP-related protein kinase A signaling

Luchowska, Elzbieta; Kloc, Renata; Olajossy, Bartosz; Wnuk, Sebastian; Wielosz, Marian; Owe‐Larsson, Björn; Urbańska, Ewa M.

doi:10.1016/j.pnpbp.2009.02.002

Cited by 31 publications

(9 citation statements)

References 36 publications

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“…The increase of KYNA reported here is comparable with the enhancement of KYNA synthesis (150-250%) observed also in other in vitro studies, e.g., following application of memantine, low concentrations of D,L-homocysteine, some b-adrenergic agonists or cAMP analogues, as well as after administration of b-adrenergic agonists in vivo (Luchowska et al 2005(Luchowska et al , 2009Kloc et al 2008). It is lower though, than after in vivo application of KYNA precursor, L-kynurenine together with probenecid, reported to increase brain KYNA several-fold (Miranda et al 1997;Shepard et al 2003).…”

Section: Discussionsupporting

confidence: 90%

“…Further insight into the underlying mechanisms comes from the experiments with KT 5720, an inhibitor of protein kinase A. KT 5720 has prevented an increase of KYNA production induced by 10 mM BHB in glial cultures and abolished the BHB-evoked increase of KATs expression in this paradigm. We have previously shown that the stimulatory effect of b-adrenergic agonists and memantine on KYNA production is mediated via cAMP/protein kinase A-related signal (Kloc et al 2008;Luchowska et al 2009). Possibly, similar mechanism underlies the action of BHB.…”

Section: Discussionmentioning

confidence: 99%

“…Mixed glial cell cultures were prepared from the brains of postnatal Wistar rats (days 1-2), as described previously (Luchowska et al 2009). Briefly, forebrains were stripped of meninges, chopped into small chunks, trypsinized, and seeded (one brain/75 cm 2 ) in culture flasks (Falcon, Switzerland) containing 10 ml of Basal Medium Eagle with Earle's salts (BME, Biochrom AG, Berlin), supplemented with 2 mM L-glutamine, penicillin-streptomycin (500 IU/ml-500 UG/ml; Gibco-BRL) and containing 10% heat-inactivated fetal bovine serum (Gibco, InVitrogen).…”

Section: Kyna Synthesis In Mixed Glial Culturesmentioning

confidence: 99%

“…A number of endogenous and exogenous factors influencing the central production of KYNA have been recognized. For example, mitochondrial toxins compromising the status of mitochondrial respiration, endogenous sulfur-containing amino acids and inhibitors of protein kinase A activity reduce formation of KYNA, whereas rise of intracellular cAMP level stimulates KYNA production (Urbanska et al 1997;Luchowski et al 2002;Kocki et al 2003;Luchowska et al 2005Luchowska et al , 2009Kloc et al 2008). It was also shown that hyperglycemia enhances the inhibitory effect of mitochondrial toxins and D,L-homocysteine on the central production of KYNA (Chmiel-Perzyńska et al 2007).…”

Section: Introductionmentioning

confidence: 99%

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Novel Aspect of Ketone Action: β-Hydroxybutyrate Increases Brain Synthesis of Kynurenic Acid In Vitro

et al. 2010

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Ketone bodies formed during ketogenic diet or non-treated diabetes mellitus may exert neuroprotective and antiepileptic effects. Here, we assessed the influence of ketone body, β-hydroxybutyrate (BHB) on the brain synthesis of kynurenic acid (KYNA), an endogenous antagonist of glutamatergic and α7-nicotinic receptors. In brain cortical slices and in primary glial cultures, BHB enhanced KYNA production. KT 5270, an inhibitor of protein kinase A, has prevented this action. At hypoglycemia, under pH 7.0 and 7.4, profound (15 mM BHB), but not mild (3 mM) ketosis increased synthesis of KYNA. In paradigm resembling diabetic ketoacidosis in vitro (30 mM glucose, pH 7.0), neither mild nor profound ketosis influenced the production of KYNA. At pH 7.4 and in 30 mM glucose though, both mild and severe ketonemia evoked an increase of KYNA production. The activity of KYNA biosynthetic enzymes, KAT I and KAT II, in cortical homogenate was not altered by BHB (0.05-10.0 mM). However, in cultured glial cells exposed to BHB (10 mM), the activity of KATs increased. This effect was reversed by the co-incubation of cells with KT 5270. Presented data reveal a novel mechanism of action of BHB. Increased synthesis of KYNA in the presence of BHB is most probably mediated by protein kinase A-dependent stimulation of KATs expression/activity leading to an increase of KYNA formation. Ensuing attenuation of the excessive excitatory glutamate-mediated neurotransmission may, at least in part, explain the neuroprotective actions of BHB.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Kyna Synthesis In Mixed Glial Culturesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Novel Aspect of Ketone Action: β-Hydroxybutyrate Increases Brain Synthesis of Kynurenic Acid In Vitro

et al. 2010

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“…That said, the interaction of cortisol with leptin is important, with leptin inhibiting the HPA axis and cortisol increasing leptin in healthy individuals 53. Leptin is negatively coupled to the cAMP pathways, decreasing cAMP induction of KYNA and TDO and is a significant immune regulator,54 increasing Th-1 responses 55. Leptin also has prosurvival and protective effects.…”

Section: Immunological Conceptualizations Of Depressionmentioning

confidence: 99%

Postpartum depression: psychoneuroimmunological underpinnings and treatment

Anderson¹,

Maes²

2013

NDT

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Postpartum depression (PPD) is common, occurring in 10%–15% of women. Due to concerns about teratogenicity of medications in the suckling infant, the treatment of PPD has often been restricted to psychotherapy. We review here the biological underpinnings to PPD, suggesting a powerful role for the tryptophan catabolites, indoleamine 2,3-dixoygenase, serotonin, and autoimmunity in mediating the consequences of immuno-inflammation and oxidative and nitrosative stress. It is suggested that the increased inflammatory potential, the decreases in endogenous anti-inflammatory compounds together with decreased omega-3 poly-unsaturated fatty acids, in the postnatal period cause an inflammatory environment. The latter may result in the utilization of peripheral inflammatory products, especially kynurenine, in driving the central processes producing postnatal depression. The pharmacological treatment of PPD is placed in this context, and recommendations for more refined and safer treatments are made, including the better utilization of the antidepressant, and the anti-inflammatory and antioxidant effects of melatonin.

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Metabolic Syndrome, Alzheimer Disease, Schizophrenia, and Depression: Role for Leptin, Melatonin, Kynurenine Pathways, and Neuropeptides

Anderson¹,

Maes²

2013

Metabolic Syndrome and Neurological Disorders

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β-adrenergic enhancement of brain kynurenic acid production mediated via cAMP-related protein kinase A signaling

Cited by 31 publications

References 36 publications

Novel Aspect of Ketone Action: β-Hydroxybutyrate Increases Brain Synthesis of Kynurenic Acid In Vitro

Novel Aspect of Ketone Action: β-Hydroxybutyrate Increases Brain Synthesis of Kynurenic Acid In Vitro

Postpartum depression: psychoneuroimmunological underpinnings and treatment

Metabolic Syndrome, Alzheimer Disease, Schizophrenia, and Depression: Role for Leptin, Melatonin, Kynurenine Pathways, and Neuropeptides

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