2. Academic Validation
  3. 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

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

  • Schizophr Bull. 2020 Dec 1;46(6):1471-1481. doi: 10.1093/schbul/sbaa074.
Martina Ulivieri 1,  Joanna Monika Wierońska 2,  Luana Lionetto 3,  Katiuscia Martinello 1,  Paulina Cieslik 2,  Agnieszka Chocyk 2,  Martina Curto 4 5 6,  Luisa Di Menna 1,  Luisa Iacovelli 7,  Anna Traficante 1,  Francesca Liberatore 7,  Giada Mascio 1,  Nico Antenucci 7,  Giuseppe Giannino 8,  Matteo Vergassola 9,  Anna Pittaluga 9 10,  Valeria Bruno 1 7,  Giuseppe Battaglia 1 7,  Sergio Fucile 1 7,  Maurizio Simmaco 3,  Ferdinando Nicoletti 1 7,  Andrzej Pilc 2,  Francesco Fazio 1
Affiliations

Affiliations

  • 1 I.R.C.C.S. Neuromed, Pozzilli, Italy.
  • 2 Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
  • 3 Department of Medical-Surgical Sciences and Translational Medicine, DiMA (Advanced Molecular Diagnosis), Sant'Andrea Hospital-Sapienza University, Rome, Italy.
  • 4 Department of Neurology and Psychiatry, Sapienza University, Rome, Italy.
  • 5 Department of Clinical and Molecular Medicine, Sapienza University, Rome, Italy.
  • 6 Bipolar & Psychotic Disorders Program, McLean Hospital, Belmont, MA.
  • 7 Department of Physiology and Pharmacology, Sapienza University, Rome, Italy.
  • 8 School of Medicine and Psychology NESMOS Department, Sant'Andrea Hospital, Sapienza University, Rome, Italy.
  • 9 Department of Pharmacy, DiFAR, University of Genoa, Genoa, Italy.
  • 10 I.R.C.C.S. San Martino Hospital, Genoa, Italy.
PMID: 32506121 DOI: 10.1093/schbul/sbaa074
Abstract

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.

Keywords

HPLC-mass; MK-801; behavior; electrophysiology; endogenous metabolite; human tissue; kynurenine pathway; mass; metabotropic glutamate receptor; mood disorder.

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