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

Ulivieri, Martina; Wierońska, Joanna M.; Lionetto, Luana; Martinello, Katiuscia; Cieślik, Paulina; Chocyk, Agnieszka; Curto, Martina; Menna, Luisa Di; Iacovelli, Luisa; Traficante, Anna; Liberatore, Francesca; Mascio, Giada; Antenucci, Nico; Giannino, Giuseppe; Vergassola, Matteo; Pittaluga, Anna; Bruno, Valeria; Battaglia, Giuseppe; Fucile, Sergio; Simmaco, Maurizio; Nicoletti, Ferdinando; Pilc, Andrzej; Fazio, Francesco

doi:10.1093/schbul/sbaa074

Cited by 23 publications

(18 citation statements)

References 53 publications

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“…And this may possibly explain the differences observed for the effects of different doses of AMPH or LSDX evaluated here. Furthermore, lipid metabolism in SCZ might be related not just to the aberration of neural pathways, but also to disturbances in the tryptophan-kynurenine metabolic pathway [6][7][8], which may warrant future investigation.…”

Section: Discussionmentioning

confidence: 99%

“…Although antipsychotic drugs can control the main symptoms of SCZ, the disease progression is not stopped by long-term treatments with antipsychotics [5]. Another pathway implicated in SCZ pathophysiology is the kynurenine pathway (KP), which involves the tryptophan metabolism [6]. The KP metabolites modulate neurotransmitters related to cognition [7].…”

Section: Introductionmentioning

confidence: 99%

“…The KP metabolites modulate neurotransmitters related to cognition [7]. Individuals with MDs presented lower levels of kynurenines, which may be involved in cognitive impairment [8], while conversely, SCZ patients showed increased kynurenine levels [6,8]. Therefore, tryptophankynurenine metabolism in psychiatric disease is well established, and disturbance of the tryptophan-kynurenine metabolic pathway might be a promising target to unravel the therapeutic effects of psychoactive drugs.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, tryptophankynurenine metabolism in psychiatric disease is well established, and disturbance of the tryptophan-kynurenine metabolic pathway might be a promising target to unravel the therapeutic effects of psychoactive drugs. Additionally, the KP is also related to lipid metabolism [6,7].…”

Section: Introductionmentioning

confidence: 99%

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Effects of Psychostimulants and Antipsychotics on Serum Lipids in an Animal Model for Schizophrenia

et al. 2021

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Schizophrenia (SCZ) treatment is essentially limited to the use of typical or atypical antipsychotic drugs, which suppress the main symptoms of this mental disorder. Metabolic syndrome is often reported in patients with SCZ under long-term drug treatment, but little is known about the alteration of lipid metabolism induced by antipsychotic use. In this study, we evaluated the blood serum lipids of a validated animal model for SCZ (Spontaneously Hypertensive Rat, SHR), and a normal control rat strain (Normotensive Wistar Rat, NWR), after long-term treatment (30 days) with typical haloperidol (HAL) or atypical clozapine (CLZ) antipsychotics. Moreover, psychostimulants, amphetamine (AMPH) or lisdexamfetamine (LSDX), were administered to NWR animals aiming to mimic the human first episode of psychosis, and the effects on serum lipids were also evaluated. Discrepancies in lipids between SHR and NWR animals, which included increased total lipids and decreased phospholipids in SHR compared with NWR, were similar to the differences previously reported for SCZ patients relative to healthy controls. Administration of psychostimulants in NWR decreased omega-3, which was also decreased in the first episode of psychosis of SCZ. Moreover, choline glycerophospholipids allowed us to distinguish the effects of CLZ in SHR. Thus, changes in the lipid metabolism in SHR seem to be reversed by the long-term treatment with the atypical antipsychotic CLZ, which was under the same condition described to reverse the SCZ-like endophenotypes of this validated animal model for SCZ. These data open new insights for understanding the potential influence of the treatment with typical or atypical antipsychotics on circulating lipids. This may represent an outcome effect from metabolic pathways that regulate lipids synthesis and breakdown, which may be reflecting a cell lipids dysfunction in SCZ.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effects of Psychostimulants and Antipsychotics on Serum Lipids in an Animal Model for Schizophrenia

et al. 2021

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“…Other KP metabolites such as XA and CA were rarely documented. An extremely low concentration of CA was reported to have anti-psychotic activities in mice and the levels of CA was reduced in the prefrontal cortex in patients with schizophrenia [131]. The glutamatergic nervous system was proposed to be a therapeutic biomarker for mood disorders including depression [132].…”

Section: Conclusion and Future Perspectivementioning

confidence: 99%

Searching for Peripheral Biomarkers in Neurodegenerative Diseases: The Tryptophan-Kynurenine Metabolic Pathway

Török

Tanaka

Vécsei

2020

Preprint

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Neurodegenerative diseases are multifactorial, initiated by a series of the causative complex which develops into a certain clinical picture. The pathogenesis and disease course vary from patient to patient. Thus, it should be likewise to the treatment. Peripheral biomarkers are to play a central role for tailoring a personalized therapeutic plan for patients who suffered from neurodegenerative diseases such as Alzheimer’s diseases, Parkinson’s disease, and multiple sclerosis, among others. Nevertheless, the use of biomarkers in clinical practice is still underappreciated and data presented in biomarker research for clinical use is still uncompelling, compared to abundant data available for drug research and development. So is the case with kynurenines (KYNs) and the kynurenine pathway (KP) enzymes which have been associated with a wide range of diseases including cancer, autoimmune diseases, inflammatory diseases, neurologic diseases, and psychiatric disorders. This review article discusses current knowledge of the KP alteration observed in the central nervous system as well as the periphery, its involvement in pathogenesis and disease progression, and emerging evidence of roles of microbiota to the gut-brain axis, searching for practical peripheral biomarkers which ensure personalized treatment plans for neurodegenerative diseases.

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A Review of the Chemistry and Biological Activities of Natural Colorants, Dyes, and Pigments: Challenges, and Opportunities for Food, Cosmetics, and Pharmaceutical Application

Pasdaran

Zare

Hamedi

et al. 2023

Chemistry & Biodiversity

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Natural pigments are important sources for the screening of bioactive lead compounds. This article reviewed the chemistry and therapeutic potentials of over 570 colored molecules from plants, fungi, bacteria, insects, algae, and marine sources. Moreover, related biological activities, advanced extraction, and identification approaches were reviewed. A variety of biological activities, including cytotoxicity against cancer cells, antioxidant, anti‐inflammatory, wound healing, anti‐microbial, antiviral, and anti‐protozoal activities, have been reported for different pigments. Considering their structural backbone, they were classified as naphthoquinones, carotenoids, flavonoids, xanthones, anthocyanins, benzotropolones, alkaloids, terpenoids, isoprenoids, and non‐isoprenoids. Alkaloid pigments were mostly isolated from bacteria and marine sources, while flavonoids were mostly found in plants and mushrooms. Colored quinones and xanthones were mostly extracted from plants and fungi, while colored polyketides and terpenoids are often found in marine sources and fungi. Carotenoids are mostly distributed among bacteria, followed by fungi and plants. The pigments isolated from insects have different structures, but among them, carotenoids and quinone/xanthone are the most important. Considering good manufacturing practices, the current permitted natural colorants are: Carotenoids (canthaxanthin, β‐carotene, β‐apo‐8′‐carotenal, annatto, astaxanthin) and their sources, lycopene, anthocyanins, betanin, chlorophyllins, spirulina extract, carmine and cochineal extract, henna, riboflavin, pyrogallol, logwood extract, guaiazulene, turmeric, and soy leghemoglobin.

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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

Cited by 23 publications

References 53 publications

Effects of Psychostimulants and Antipsychotics on Serum Lipids in an Animal Model for Schizophrenia

Effects of Psychostimulants and Antipsychotics on Serum Lipids in an Animal Model for Schizophrenia

Searching for Peripheral Biomarkers in Neurodegenerative Diseases: The Tryptophan-Kynurenine Metabolic Pathway

A Review of the Chemistry and Biological Activities of Natural Colorants, Dyes, and Pigments: Challenges, and Opportunities for Food, Cosmetics, and Pharmaceutical Application

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