دورية أكاديمية
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Differentially regulated targets in the fast-acting antidepressant effect of (R)-ketamine: A systems biology approach.

التفاصيل البيبلوغرافية
العنوان: Differentially regulated targets in the fast-acting antidepressant effect of (R)-ketamine: A systems biology approach.
المؤلفون: Scotton E; Laboratory of Molecular Psychiatry, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil; Pharmacology Department and Graduate Program in Biological Sciences: Pharmacology and Therapeutics, Institute of Health Sciences, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil. Electronic address: escotton@hcpa.edu.br., Casa PL; Institute of Biotechnology, Universidade de Caxias do Sul (UCS), Caxias do Sul, RS, Brazil. Electronic address: plcasa@ucs.br., de Abreu FP; Institute of Biotechnology, Universidade de Caxias do Sul (UCS), Caxias do Sul, RS, Brazil. Electronic address: fpabreu1@ucs.br., de Avila E Silva S; Institute of Biotechnology, Universidade de Caxias do Sul (UCS), Caxias do Sul, RS, Brazil. Electronic address: sasilva6@ucs.br., Wilges RLB; Laboratory of Molecular Psychiatry, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil., Rossetto MV; Institute of Biotechnology, Universidade de Caxias do Sul (UCS), Caxias do Sul, RS, Brazil. Electronic address: mvrossetto@ucs.br., Géa LP; Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada., Rosa AR; Laboratory of Molecular Psychiatry, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil; Pharmacology Department and Graduate Program in Biological Sciences: Pharmacology and Therapeutics, Institute of Health Sciences, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil; Department of Psychiatry and Graduate Program in Psychiatry and Behavioral Sciences, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil. Electronic address: arrosa@hcpa.edu.br., Colombo R; Institute of Biotechnology, Universidade de Caxias do Sul (UCS), Caxias do Sul, RS, Brazil. Electronic address: rcolombo1@ucs.br.
المصدر: Pharmacology, biochemistry, and behavior [Pharmacol Biochem Behav] 2023 Feb; Vol. 223, pp. 173523. Date of Electronic Publication: 2023 Jan 30.
نوع المنشور: Systematic Review; Journal Article; Review; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: United States NLM ID: 0367050 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-5177 (Electronic) Linking ISSN: 00913057 NLM ISO Abbreviation: Pharmacol Biochem Behav Subsets: MEDLINE
أسماء مطبوعة: Publication: Tarrytown, NY : Elsevier
Original Publication: Phoenix, N. Y. Ankho International, ltd.
مواضيع طبية MeSH: Ketamine*/pharmacology , Depressive Disorder, Major*/drug therapy, Humans ; Depression/drug therapy ; Systems Biology ; Antidepressive Agents/pharmacology ; Receptors, AMPA/metabolism ; Receptors, N-Methyl-D-Aspartate/metabolism
مستخلص: Approximately two-thirds of patients with major depressive disorder (MDD) fail to respond to conventional antidepressants, suggesting that additional mechanisms are involved in the MDD pathophysiology. In this scenario, the glutamatergic system represents a promising therapeutic target for treatment-resistant depression. To our knowledge, this is the first study using semantic approach with systems biology to identify potential targets involved in the fast-acting antidepressant effects of ketamine and its enantiomers as well as identifying specific targets of (R)-ketamine. We performed a systematic review, followed by a semantic analysis and functional gene enrichment to identify the main biological processes involved in the therapeutic effects of these agents. Protein-protein interaction networks were constructed, and the genes exclusively regulated by (R)-ketamine were explored. We found that the regulation of α-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid (AMPA) receptor and N-methyl-d-aspartate (NMDA) receptor subunits-Postsynaptic Protein 95 (PSD-95), Brain Derived Neurotrophic Factor (BDNF), and Tyrosine Receptor Kinase B (TrkB) are shared by the three-antidepressant agents, reinforcing the central role of the glutamatergic system and neurogenesis on its therapeutic effects. Differential regulation of Transforming Growth Factor Beta 1 (TGF-β1) receptors-Mitogen-Activated Protein Kinases (MAPK's), Receptor Activator of Nuclear Factor-Kappa Beta Ligand (RANKL), and Serotonin Transporter (SERT) seems to be particularly involved in (R)-ketamine antidepressant effects. Our data helps further studies investigating the relationship between these targets and the mechanisms of (R)-ketamine and searching for other therapeutic compounds that share the regulation of these specific biomolecules. Ultimately, this study could contribute to improve the fast management of depressive-like symptoms with less detrimental side effects than ketamine and (S)-ketamine.
Competing Interests: Declaration of competing interest The authors declare no conflicts of interest.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
فهرسة مساهمة: Keywords: (R)-ketamine; Glutamatergic synapse; Ketamine enantiomers; Molecular targets; Rapid antidepressant effects; Systems biology
المشرفين على المادة: 690G0D6V8H (Ketamine)
0 (Antidepressive Agents)
0 (Receptors, AMPA)
0 (Receptors, N-Methyl-D-Aspartate)
تواريخ الأحداث: Date Created: 20230202 Date Completed: 20230314 Latest Revision: 20230423
رمز التحديث: 20231215
DOI: 10.1016/j.pbb.2023.173523
PMID: 36731751
قاعدة البيانات: MEDLINE
الوصف
تدمد:1873-5177
DOI:10.1016/j.pbb.2023.173523