TY - JOUR
T1 - The Trace Kynurenine, Cinnabarinic Acid, Displays Potent Antipsychotic-Like Activity in Mice and Its Levels Are Reduced in the Prefrontal Cortex of Individuals Affected by Schizophrenia
AU - Ulivieri, Martina
AU - Wierońska, Joanna Monika
AU - Lionetto, Luana
AU - Martinello, Katiuscia
AU - Cieslik, Paulina
AU - Chocyk, Agnieszka
AU - Curto, Martina
AU - Di Menna, Luisa
AU - Iacovelli, Luisa
AU - Traficante, Anna
AU - Liberatore, Francesca
AU - Mascio, Giada
AU - Antenucci, Nico
AU - Giannino, Giuseppe
AU - Vergassola, Matteo
AU - Pittaluga, Anna
AU - Bruno, Valeria
AU - Battaglia, Giuseppe
AU - Fucile, Sergio
AU - Simmaco, Maurizio
AU - Nicoletti, Ferdinando
AU - Pilc, Andrzej
AU - Fazio, Francesco
N1 - Publisher Copyright:
© 2020 The Author(s) 2020. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.
PY - 2020/11/1
Y1 - 2020/11/1
N2 - Cinnabarinic acid (CA) is a kynurenine metabolite that activates mGlu4 metabotropic glutamate receptors. Using a highly sensitive ultra-performance liquid chromatography/tandem mass spectrometry (UPLC/MS-MS) method, we found that CA is present in trace amounts in human brain tissue. CA levels were largely reduced in the prefrontal cortex (PFC) of individuals affected by schizophrenia. This reduction did not correlate with age, sex, duration of the disease, and duration and type of antipsychotic medication and might, therefore, represent a trait of schizophrenia. Interestingly, systemic treatment with low doses of CA (<1 mg/kg, i.p.) showed robust efficacy in several behavioral tests useful to study antipsychotic-like activity in mice and rats and attenuated MK-801-evoked glutamate release. CA failed to display antipsychotic-like activity and inhibit excitatory synaptic transmission in mice lacking mGlu4 receptors. These findings suggest that CA is a potent endogenous antipsychotic-like molecule and reduced CA levels in the PFC might contribute to the pathophysiology of schizophrenia.
AB - Cinnabarinic acid (CA) is a kynurenine metabolite that activates mGlu4 metabotropic glutamate receptors. Using a highly sensitive ultra-performance liquid chromatography/tandem mass spectrometry (UPLC/MS-MS) method, we found that CA is present in trace amounts in human brain tissue. CA levels were largely reduced in the prefrontal cortex (PFC) of individuals affected by schizophrenia. This reduction did not correlate with age, sex, duration of the disease, and duration and type of antipsychotic medication and might, therefore, represent a trait of schizophrenia. Interestingly, systemic treatment with low doses of CA (<1 mg/kg, i.p.) showed robust efficacy in several behavioral tests useful to study antipsychotic-like activity in mice and rats and attenuated MK-801-evoked glutamate release. CA failed to display antipsychotic-like activity and inhibit excitatory synaptic transmission in mice lacking mGlu4 receptors. These findings suggest that CA is a potent endogenous antipsychotic-like molecule and reduced CA levels in the PFC might contribute to the pathophysiology of schizophrenia.
KW - HPLC-mass
KW - MK-801
KW - behavior
KW - electrophysiology
KW - endogenous metabolite
KW - human tissue
KW - kynurenine pathway
KW - mass
KW - metabotropic glutamate receptor
KW - mood disorder
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U2 - 10.1093/schbul/sbaa074
DO - 10.1093/schbul/sbaa074
M3 - Article
C2 - 32506121
AN - SCOPUS:85094194023
SN - 0586-7614
VL - 46
SP - 1471
EP - 1481
JO - Schizophrenia Bulletin
JF - Schizophrenia Bulletin
IS - 6
ER -
