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

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

Content Provider	Springer Nature Link
Author	Chmiel Perzyńska, Iwona Kloc, Renata Perzyński, Adam Rudzki, Sławomir Urbańska, Ewa M.
Copyright Year	2010
Abstract	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.
Starting Page	40
Ending Page	50
Page Count	11
File Format	PDF
ISSN	10298428
Journal	Neurotoxicity Research
Volume Number	20
Issue Number	1
e-ISSN	14763524
Language	English
Publisher	Springer-Verlag
Publisher Date	2010-09-14
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Rat brain Kynurenic acid Ketogenic diet Ketoacidosis β-Hydroxybutyrate Protein kinase A Neurochemistry Neurosciences Cell Biology Neurobiology Pharmacology/Toxicology Neurology
Content Type	Text
Resource Type	Article
Subject	Neuroscience Toxicology

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