4 results on '"Comai, Stefano"'
Search Results
2. The kynurenine pathway in treatment-resistant schizophrenia at the crossroads between pathophysiology and pharmacotherapy.
- Author
-
Sapienza, Jacopo, Agostoni, Giulia, Dall'Acqua, Stefano, Sut, Stefania, Nasini, Sofia, Martini, Francesca, Marchesi, Anna, Bechi, Margherita, Buonocore, Mariachiara, Cocchi, Federica, Cavallaro, Roberto, Spangaro, Marco, Comai, Stefano, and Bosia, Marta
- Subjects
- *
KYNURENINE , *DRUG therapy , *METHYL aspartate receptors , *SCHIZOPHRENIA , *PATHOLOGICAL physiology - Abstract
Two cardinal elements in the complex and multifaceted pathophysiology of schizophrenia (SCZ) are neuroinflammation and dysregulation of glutamatergic neurotransmission, with the latter being especially involved in treatment-resistant schizophrenia (TRS). Interestingly, the Kynurenine (KYN) pathway (KP) is at the crossroad between them, constituting a potential causal link and a therapeutic target. Although there is preclinical and clinical evidence indicating a dysregulation of KP associated with the clinical phenotype of SCZ, clinical studies investigating the possible relationship between changes in biomarkers of the KP and response to pharmacotherapy are still limited. Therefore, we have studied possible differences in the circulating levels of biomarkers of the metabolism of tryptophan along the KP in 43 responders to first-line treatments (FLR) and 32 TRS patients treated with clozapine, and their possible associations with psychopathology in the two subgroups. Plasma levels of KYN were significantly higher in TRS patients than in FLR patients, indicating a greater activation of KP. Furthermore, the levels of quinolinic (NMDA receptor agonist) and kynurenic acid (NMDA negative allosteric modulator) showed a negative and a positive correlation with several dimensions and the overall symptomatology in the whole sample and in FLR, but not in TRS, suggesting a putative modulating effect of clozapine elicited through the NMDA receptors. Despite the cross-sectional design of the study that prevents us from demonstrating causation, these findings show a significant relationship among circulating KP biomarkers, psychopathology, and response to pharmacotherapy in SCZ. Therefore, plasma KP biomarkers should be further investigated for developing personalized medicine approaches in SCZ. • Higher levels of KYN found in TRS point out a greater activation of the KP in TRS. • Levels of QUIN are negatively associated with the severity of symptoms only in FLRs. • KYNA/QUIN ratio shows a positive correlation with the symptomatology only in FLRs. • Clozapine probably nullifies the impact of QUINA and KYNA on symptoms in TRS. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
3. Grey and white matter structure associates with the activation of the tryptophan to kynurenine pathway in bipolar disorder.
- Author
-
Poletti, Sara, Melloni, Elisa, Aggio, Veronica, Colombo, Cristina, Valtorta, Flavia, Benedetti, Francesco, and Comai, Stefano
- Subjects
- *
BIPOLAR disorder , *INDOLEAMINE 2,3-dioxygenase , *TRYPTOPHAN , *CORPUS callosum , *QUINOLINIC acid - Abstract
Background: Bipolar disorder (BD) is a severe mental illness characterised by reduced grey matter (GM) volumes and cortical thickness, and disrupted white matter (WM) microstructure. Activation of indoleamine 2,3-dioxygenase following a pro-inflammatory state could increase the amount of tryptophan (Trp) converted to kynurenine (Kyn) possibly leading to the production of detrimental catabolites of the Kyn pathway with neurotoxic effects. We investigated if peripheral levels of Trp-and Kyn and the breakdown of Trp-into Kyn (Kyn/Trp-ratio) are related to WM and GM integrity in BD.Methods: Peripheral levels of Trp-and Kyn were analysed in 72 patients with BD and 33 controls. Patients also underwent MRI in a Philips 3T scanner.Results: Patients showed higher Kyn levels and Kyn/Trp-ratio compared to controls. MRI analyses performed in patients with BD showed a negative association between the Kyn/Trp-ratio and the integrity of corpus callosum microstructure, the volume of the amygdala and cortical thickness in fronto-parietal regions.Limitation: The lack of information on the levels of downstream metabolites of Kyn prevent us to confirm the possible unbalance between quinolinic and kynurenic acids as well as their possible relationship with changes in GM and WM markers. The activation of the Kyn pathway as suggested by the increased Kyn/Trp-ratio may lead to an imbalance of the neurotoxic vs the neuroprotective arm of the biochemical pathway, resulting in significant changes in GM and WM regions of brain areas strongly implicated in the pathophysiology of BD, such as amygdala and corpus callosum. [ABSTRACT FROM AUTHOR]- Published
- 2019
- Full Text
- View/download PDF
4. The effect of age on the enzyme activities of tryptophan metabolism along the kynurenine pathway in rats
- Author
-
Stefano Comai, Carlo Virgilio Luigi Costa, Eugenio Ragazzi, Antonella Bertazzo, Graziella Allegri, Comai, Stefano, Costa, Cvl, Ragazzi, E., Bertazzo, A, and Allegri, G.
- Subjects
medicine.medical_specialty ,Kynurenine pathway ,Carboxy-Lyases ,Clinical Biochemistry ,Kynurenine—oxoglutarate transaminase ,Kidney ,Biochemistry ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Internal medicine ,Intestine, Small ,medicine ,Animals ,Kynurenine ,Transaminases ,biology ,Biochemistry (medical) ,Tryptophan ,Age Factors ,General Medicine ,Metabolism ,Enzyme assay ,Enzymes ,Rats ,Endocrinology ,chemistry ,Liver ,Ageing ,biology.protein ,Oxygenases ,Quinolinic acid - Abstract
Background Quinolinic acid and other kynurenine metabolites of the oxidative metabolism of tryptophan play an important role in several pathophysiological conditions. We aimed to study the effect of age on the enzyme activities of tryptophan metabolism along the kynurenine pathway. Methods Enzyme activity was investigated in liver, kidneys and small intestine obtained from Sprague–Dawley rats of various ages (1 week, 2–3, 12 and 18 months). Results We found age-related differences in the liver tryptophan 2,3-dioxygenase, small intestine indole 2,3-dioxygenase, liver and kidney kynurenine 3-monooxygenase activities, which decreased significantly with age. Also liver kynureninase activity declined with age, while the activity in kidneys did not show an evident age-related pattern from 2–3 months to 18 months of age. Liver kynurenine oxoglutarate transaminase was quite similar through all considered age groups, while the activity in kidneys was significantly lower in newborn rats and progressively increased up to 12 months, then significantly decreased at 18 months of age. Liver and kidney 3-hydroxyanthranilate 3,4-dioxygenase progressively and significantly increased from newborns to 12 months of age; in the group of rats aged 18 months, the enzyme activity tended to diminish, although not significantly. The liver aminocarboxymuconate-semialdehyde decarboxylase activity increased up to 12 months of age, then tended to decrease at 18 months, while in the kidneys, in which the activity was higher than in the liver at all the considered ages, the activity remained constantly elevated from 2–3 months to 18 months of age. Conclusions A progressive decline in the enzyme activities involved in tryptophan metabolism along the kynurenine pathway in rat tissues was found with age, except for aminocarboxymuconate-semialdehyde decarboxylase, which, on the contrary, was increased after 2–3 months to the other older groups of age. The altered metabolism of tryptophan with ageing can lead to a decreased biosynthesis of nicotinic acid, tryptophan being the major source of body stores of NAD coenzymes, which are involved in almost all biogenetic and biosynthetic pathways of the organism.
- Published
- 2005
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.