Jéferson Ferraz Goularte

Laboratory of Molecular Psychiatry, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil; Department of Psychiatry and Graduate Program in Psychiatry and Behavioral Sciences, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil. Electronic address: jefgoularte@hcpa.edu.br.

2 papers in the library · 36 citations · publishing 2022-2024

Papers

Is (R)-ketamine a Potential Therapeutic Agent for Treatment-Resistant Depression with Less Detrimental Side Effects? A Review of Molecular Mechanisms Underlying Ketamine and its Enantiomers.

Biochemical Pharmacology February 1, 2022 Ellen Scotton, Bárbara Antqueviezc, Mailton Vasconcelos et al. 35 citations

About one-third of people with major depressive disorder do not respond to standard antidepressants, and even those who do respond may wait weeks for effects. Ketamine, a mixture of two enantiomers, (R)-ketamine and (S)-ketamine, blocks NMDARs and shows rapid antidepressant effects in treatment-resistant depression. Preclinical evidence indicates (R)-ketamine has lower NMDAR affinity but greater and longer-lasting antidepressant potency with fewer side effects than racemic ketamine or (S)-ketamine. Ketamine and its enantiomers also modulate synaptogenesis and neurotransmission. This review summarizes current evidence on neurotransmission, neuroplasticity, and neural network activity as mechanisms, highlighting intracellular signaling pathways involving mTOR, ERK, and BDNF, and discusses probable mechanisms behind side effects.

DOI: 10.1016/j.bcp.2022.114963 Medicine

Molecular signature underlying (R)-ketamine rapid antidepressant response on anhedonic-like behavior induced by sustained exposure to stress.

Pharmacology, biochemistry, and behavior December 1, 2024 Ellen Scotton, Paola Rampelotto Ziani, Renata Luiza Boff Wilges et al. 1 citation

Anhedonia, a core symptom of major depressive disorder, was studied in male Wistar rats exposed to chronic variable stress. Rats classified as anhedonic-like showed reduced sucrose preference, which was reversed by a single dose of (R)-ketamine. High-throughput proteomics of the prefrontal cortex revealed that anhedonia was linked to downregulation of Neuronal Pentraxin Receptor and Galectin-1, suggesting disruption in inflammatory response, neurotransmitter activity, and glutamatergic synapses. (R)-ketamine response was associated with novel protein targets involved in oxidative stress, energy metabolism, synaptogenesis, dendritic arborization, neuroinflammation, gene expression, and telomere length. These pathways overlap with known depression pathophysiology and may offer therapeutic targets for anhedonia.

DOI: 10.1016/j.pbb.2024.173882 Full text Major depressive disorder R-ketamine treatment response Anhedonic-like behavior Molecular targets +6