Review
Neurosciences
George M. Anderson, Isabella Bruno-Pacella
Summary: This article assesses the bioeffect of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) and compares them using neuroimaging and in vitro measurements. The study finds that these drugs typically result in a 70-90% reduction in platelet serotonin (5-HT) content. The bioeffect is similar among different types of SSRIs and SNRIs and is consistent with other assessment methods.
PSYCHOPHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Suresh Paudel, Eunae Kim, Anlin Zhu, Srijan Acharya, Xiao Min, Seung Hoon Cheon, Kyeong-Man Kim
Summary: This study identified the diverse effects of synthetic 4-benzylpiperidine carboxamides on serotonin, norepinephrine, and dopamine reuptake, as well as the critical structural features contributing to the selectivity of these molecules for each of the monoamine transporters. Additionally, the study found that specific residues on the compounds bound to the transporters and highlighted the functional role of a dopamine reuptake inhibitor in regulating dopamine D-2 receptor function.
BIOMOLECULES & THERAPEUTICS
(2021)
Article
Pharmacology & Pharmacy
Juhee Lim, Yeojin Bang, Kyeong-Man Kim, Hyun Jin Choi
Summary: This study investigated the effects of differentiation on the serotonergic neuronal phenotype of the mouse hippocampal neuronal cell line HT22. The results showed that differentiation promoted neurite outgrowth and upregulation of N-methyl-D-aspartate receptor and choline acetyltransferase in HT22 cells. Furthermore, proteins required for serotonergic neurotransmission were significantly upregulated in differentiated HT22 cells. These findings suggest that differentiated HT22 cells have enhanced functional serotonergic properties and could be used for assessing the efficacy of antidepressant 5-HT reuptake inhibitors.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Cardiac & Cardiovascular Systems
Anna Calvi, Ilaria Fischetti, Ignazio Verzicco, Martino Belvederi Murri, Stamatula Zanetidou, Riccardo Volpi, Pietro Coghi, Stefano Tedeschi, Mario Amore, Aderville Cabassi
Summary: Patients with depression who take antidepressant medication may have an increased risk of developing hypertension. Different types of antidepressants have varying effects on blood pressure, with selective serotonin reuptake inhibitors being the safest class, while dopamine-norepinephrine reuptake inhibitors may lead to blood pressure increases.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2021)
Article
Pharmacology & Pharmacy
Takashi Sonobe, Tsuyoshi Akiyama, James T. Pearson
Summary: This study used microdialysis technique to investigate the contribution of carrier-mediated 5-HT efflux to the elevation of interstitial 5-HT levels in the heart during myocardial ischemia. The results showed that reverse transport of 5-HT via SERT, caused by impaired ion gradients, plays a significant role in the increase of interstitial 5-HT during ischemia. Pharmacological agents such as sodium cyanide, ouabain, and reserpine were found to induce a rise in 5-HT levels in the dialysate, suggesting the presence of carrier-mediated 5-HT efflux in the heart.
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
(2021)
Article
Clinical Neurology
George M. Anderson, Christine M. Ramsey, Kevin G. Lynch, Joel Gelernter, David W. Oslin
Summary: This study investigated the distribution of baseline platelet serotonin (5-HT) levels in depression patients seeking treatment and defined subgroups based on drug exposure. The bioeffect of 5-HT reuptake inhibitors (SRIs) and the relationship between demographic variables and platelet 5-HT concentration were also assessed. Data from a cross-sectional study of 1433 Veterans Administration (VA) patients were analyzed, revealing a bimodal distribution of platelet 5-HT levels and significant differences in population, sex, and age.
JOURNAL OF AFFECTIVE DISORDERS
(2023)
Article
Biochemistry & Molecular Biology
Soumava Santra, Sandhya Kortagere, Seenuvasan Vedachalam, Sanjib Gogoi, Tamara Antonio, Maarten E. A. Reith, Aloke K. Dutta
Summary: The study revealed a significant influence from the alteration of the stereochemistry of the hydroxyl group on the pyran ring of D-473 on transporters affinities, indicating stereospecific preference for interaction. Furthermore, novel compounds such as D-528 and D-529 were identified as some of the most potent dopamine-norepinephrine reuptake inhibitors known to-date. Computational analysis found that the nature of interactions from molecular docking experiments correlated well with the affinities of the compounds for the transporters.
ACS CHEMICAL NEUROSCIENCE
(2021)
Review
Anesthesiology
Li Wang, Joshua Tobe, Emily Au, Cody Tran, Jane Jomy, Yvgeniy Oparin, Rachel J. Couban, James Paul
Summary: The systematic review and meta-analysis found that SSRIs and SNRIs as adjuncts for postoperative pain management significantly reduced postoperative pain, opioid consumption, and improved patient satisfaction without increasing adverse events compared with placebo. SSRIs tend to be less effective than SNRIs, but the effects of SSRIs remain inconclusive due to limited evidence.
BRITISH JOURNAL OF ANAESTHESIA
(2022)
Article
Biochemistry & Molecular Biology
Yuying Huang, Hong Chen, Shao-Rui Chen, Hui-Lin Pan
Summary: Antidepressants, such as duloxetine and amitriptyline, are effective for treating chronic neuropathic pain by inhibiting norepinephrine and serotonin transporters and activating alpha 1-and alpha 2-adrenergic receptors in the spinal cord. This study provides important insights into the mechanism of action of antidepressants in alleviating neuropathic pain and can inform the development of improved treatment strategies.
ACS CHEMICAL NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Yuying Huang, Hong Chen, Shao-Rui Chen, Hui -Lin Pan
Summary: Antidepressants are effective for treating chronic neuropathic pain by inhibiting glutamatergic input through activation of α1 and α2 adrenergic receptors.
ACS CHEMICAL NEUROSCIENCE
(2023)
Review
Medicine, General & Internal
Agoston Patthy, Janos Murai, Janos Hanics, Anna Pinter, Peter Zahola, Tomas G. M. Hokfelt, Tibor Harkany, Alan Alpar
Summary: Alzheimer's disease (AD) is a devastating neurodegenerative disorder for which an effective therapy has yet to be found. Research suggests that early damage to the ascending monoaminergic system in the brainstem may be an early sign and potential trigger of AD. In addition, cortical malfunction and local neurohistopathology are also related to the progression of AD.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Rachel A. Davies, Vy T. Nguyen, Jose M. Eltit, Richard A. Glennon
Summary: a-Pyrrolidinohexiophenone (a-PHP) is a synthetic cathinone central stimulant that is structurally similar to a-PVP. It is a potent dopamine transporter (DAT) reuptake inhibitor. In this study, a series of 4-substituted a-PHP analogues were examined, and most showed selective DAT reuptake inhibition with a narrow range of potency. The 4-CF3 analogue was an outlier with reduced potency and selectivity. QSAR study was not possible due to limited empirical results.
ACS CHEMICAL NEUROSCIENCE
(2023)
Article
Neurosciences
Lindsay J. Agostinelli, Scott C. Seaman, Clifford B. Saper, Dustin P. Fykstra, Marco M. Hefti, Timothy R. Koscik, Brian J. Dlouhy, Alexander G. Bassuk
Summary: Researchers report a study that combines high-resolution MRI and detailed histology to study the impact of neurologic disease on specific cell groups in the human brainstem and cerebellum. These findings are crucial for understanding and diagnosing brainstem lesions.
JOURNAL OF NEUROSCIENCE
(2023)
Review
Neurosciences
Cooper D. Grossman, Jeremiah Y. Cohen
Summary: This article discusses the evolution of nervous systems to adapt to the dynamics of the environment and explains this process through the study of learning and decision-making. The article focuses on the slow dynamics of neuronal networks and the role of neuromodulators in temporal scaling.
ANNUAL REVIEW OF NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Predrag Kalaba, Katharina Pacher, Philip John Neill, Vladimir Dragacevic, Martin Zehl, Judith Wackerlig, Michael Kirchhofer, Simone B. Sartori, Hubert Gstach, Shima Kouhnavardi, Anna Fabisikova, Matthias Pillwein, Francisco Monje-Quiroga, Karl Ebner, Alexander Prado-Roller, Nicolas Singewald, Ernst Urban, Thierry Langer, Christian Pifl, Jana Lubec, Johann Jakob Leban, Gert Lubec
Summary: The high structural similarity among dopamine, norepinephrine, and serotonin transporters, especially in transmembrane regions, presents a challenge for specifically targeting individual transporters. Ligand design is limited by chemists' tendency to modify lead compounds in a way that reduces the number of chiral centers, thus limiting the chemical space of synthetic ligands. However, increasing molecular complexity by introducing additional chiral centers has been shown to lead to more selective and potent dopamine reuptake inhibitors. The establishment of a compound library with defined absolute configurations lays the foundation for computational chemists to optimize and design specific monoamine transporter reuptake inhibitors.
Letter
Respiratory System
Mahmoud I. Abdel-Aziz, Susanne J. H. Vijverberg, Anne H. Neerincx, Paul Brinkman, Ariane H. Wagener, John H. Riley, Ana R. Sousa, Stewart Bates, Scott S. Wagers, Bertrand De Meulder, Charles Auffray, Asa M. Wheelock, Aruna T. Bansal, Massimo Caruso, Pascal Chanez, Mohib Uddin, Julie Corfield, Ildiko Horvath, Norbert Krug, Jacek Musial, Kai Sun, Dominick E. Shaw, Thomas Sandstrom, Paolo Montuschi, Stephen J. Fowler, Rene Lutter, Ratko Djukanovic, Peter Howarth, Paul Skipp, Marek Sanak, Ian M. Adcock, Kian Fan Chung, Peter J. Sterk, Aletta D. Kraneveld, Anke H. Maitland-van der Zee
EUROPEAN RESPIRATORY JOURNAL
(2022)
Article
Nutrition & Dietetics
Kirsten Szklany, Phillip A. Engen, Ankur Naqib, Stefan J. Green, Ali Keshavarzian, Alejandro Lopez Rincon, Cynthia J. Siebrand, Mara A. P. Diks, Melanie van de Kaa, Johan Garssen, Leon M. J. Knippels, Aletta D. Kraneveld
Summary: Nutritional components such as non-digestible oligosaccharides and omega-3 poly-unsaturated fatty acids can beneficially modulate the composition and activity of the intestinal microbial community. This study investigated the combined effect of scGOS:lcFOS and n-3 PUFAs on the microbial community structures in the caecal content and the development of the immune system, brain, and behavior in mice. The results showed that the combination of these components had an impact on the caecal microbiota and certain aspects of behavior and brain chemistry, but not on the immune cells.
Article
Chemistry, Medicinal
Jan Pieter Konsman
Summary: Despite the protective tissues and barriers in the brain, certain injuries or infections can lead to changes in brain function and behavior due to cytokine production and action. Peripheral infection-induced inflammation and psychological stress may also have similar effects on the central nervous system. Understanding the conditions of cytokine production and action in the brain is important for studying neuroinflammation and exploring ways to modify neural functioning.
Article
Nutrition & Dietetics
Amber Berdenis van Berlekom, Raphael Kubler, Jeske W. Hoogeboom, Danielle Vonk, Jacqueline A. Sluijs, R. Jeroen Pasterkamp, Jinte Middeldorp, Aletta D. Kraneveld, Johan Garssen, Rene S. Kahn, Elly M. Hol, Lot D. de Witte, Marco P. Boks
Summary: There is compelling evidence that nutrition has a significant impact on human brain development. Previous studies have shown that three specific amino acids, histidine, lysine, and threonine, can synergistically inhibit mTOR activity and behavior. In this pioneering study, human cerebral organoids were used to investigate the impact of amino acid supplementation on neurodevelopment. The results showed that exposure to threonine, histidine, and lysine led to decreased mTOR activity, reduced organoid size, and altered gene expression, supporting findings from previous rodent studies.
Article
Pharmacology & Pharmacy
Charlotte E. Pelgrim, Ingrid van Ark, Thea Leusink-Muis, Maike A. D. Brans, Saskia Braber, Johan Garssen, Ardy van Helvoort, Aletta D. Kraneveld, Gert Folkerts
Summary: This study describes an optimized intratracheal administration technique and compares it with oropharyngeal aspiration. The results show that the intratracheal administration technique has higher efficacy, reproducibility, and accuracy compared to oropharyngeal aspiration, and can be used to improve the research design of respiratory disease mouse models.
JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS
(2022)
Article
Medicine, General & Internal
Pantea Kiani, Jessica Balikji, Aletta D. Kraneveld, Johan Garssen, Gillian Bruce, Joris C. Verster
Summary: Two studies have shown that immune fitness before the pandemic is the most important factor in predicting the number and severity of COVID-19 symptoms. Maintaining good immune health during the pandemic is crucial for reducing the severity of symptoms.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Pharmacology & Pharmacy
Amir Hossein Alizadeh Bahmani, Elise M. A. Slob, Lizan D. Bloemsma, Susanne Brandstetter, Paula Corcuera-Elosegui, Mario Gorenjak, Susanne Harner, Simone Hashimoto, Anna M. Hedman, Michael Kabesch, Gerard H. Koppelman, Javier Korta-Murua, Aletta D. Kraneveld, Anne H. Neerincx, Marielle W. Pijnenburg, Maria Pino-Yanes, Uros Potocnik, Olaia Sardon-Prado, Susanne J. H. Vijverberg, Christine Wolff, Mahmoud Abdel-Aziz, Anke H. Maitland-van der Zee
Summary: This multicountry, observational, case-control study aimed to compare treatment regimens, inhaler techniques, medication adherence, and other characteristics of controlled and uncontrolled pediatric asthma. The study found that children in higher treatment steps had a higher risk of uncontrolled asthma, and the risk was also associated with a larger change in lung function post and pre-salbutamol. However, adherence and inhaler techniques were not related to the risk of uncontrolled asthma. Other factors, such as environmental factors and biological profiles, may influence the risk of uncontrolled asthma in this population.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Review
Medicine, General & Internal
Joris C. Verster, Aletta D. Kraneveld, Johan Garssen
Summary: Immune fitness is crucial for maintaining overall health and improving quality of life. This article provides an overview of how to assess immune fitness, including the use of a single-item rating scale and complementary tools such as the Immune Status Questionnaire and biomarker measurements. Combining immune fitness assessments with biomarker measurements is essential as individuals may not be aware of systemic inflammation.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Oncology
Yvonne Grobben, Judith E. den Ouden, Cristina Aguado, Anne M. van Altena, Aletta D. Kraneveld, Guido J. R. Zaman
Summary: Ovarian cancer, particularly high-grade serous ovarian cancer, has a highly immunosuppressive tumor microenvironment, which limits the effectiveness of immunotherapy. This study aimed to evaluate the role of amino acid-metabolizing enzymes in this environment by analyzing the levels of amino acids and corresponding metabolites in liquid biopsies of ovarian cancer patients. The enzymes IDO1 and IL4I1 were identified as active players, and a correlation between IL4I1 metabolite levels and disease stage was revealed. Further research on IL4I1 activity in ovarian cancer is needed to develop new immunotherapeutic strategies.
Article
Neurosciences
Yuanpeng Zheng, Naika Prince, Christine van Hattem, Johan Garssen, Paula Perez Pardo, Aletta D. Kraneveld
Summary: This study investigated the relation between intestinal bacteria-associated para-cresyl sulfate (pCS) and 4-ethylphenyl sulfate (4EPS) and PTEN in autism spectrum disorder (ASD). It found that pCS and 4EPS can induce ASD-like behavior in mice, but the molecular mechanisms are not known.
MOLECULAR AND CELLULAR NEUROSCIENCE
(2023)
Article
Allergy
Jelle M. Blankestijn, Alejandro Lopez-Rincon, Anne H. Neerincx, Susanne J. H. Vijverberg, Simone Hashimoto, Mario Gorenjak, Olaia Sardon Prado, Paula Corcuera-Elosegui, Javier Korta-Murua, Maria Pino-Yanes, Uros Potocnik, Corinna Bang, Andre Franke, Christine Wolff, Susanne Brandstetter, Antoaneta A. Toncheva, Parastoo Kheiroddin, Susanne Harner, Michael Kabesch, Aletta D. Kraneveld, Mahmoud Abdel-Aziz, Anke H. Maitland-van der Zee
Summary: This study aimed to investigate whether the gastrointestinal microbiome can differentiate between uncontrolled and controlled asthma in children. By analyzing samples from 143 children with moderate-to-severe asthma, it was found that machine learning, specifically REFS, can differentiate the control level of asthma in children. The results suggest that the gastrointestinal microbiome may be a potential biomarker for treatment responsiveness and help improve asthma control in children.
PEDIATRIC ALLERGY AND IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Mario Martin-Almeida, Javier Perez-Garcia, Esther Herrera-Luis, Carlos Rosa-Baez, Mario Gorenjak, Anne H. Neerincx, Olaia Sardon-Prado, Antoaneta A. Toncheva, Susanne Harner, Christine Wolff, Susanne Brandstetter, Elisa Valletta, Mahmoud Abdel-Aziz, Simone Hashimoto, Vojko Berce, Paula Corcuera-Elosegui, Javier Korta-Murua, Heike Buntrock-Doepke, Susanne J. H. Vijverberg, Joris C. Verster, Nikki Kerssemakers, Anna M. Hedman, Catarina Almqvist, Jesus Villar, Aletta D. Kraneveld, Uros Potocnik, Michael Kabesch, Anke H. Maitland-van der Zee, Maria Pino-Yanes
Summary: Asthma is a common chronic disease in children, but the influence of DNA methylation on bronchodilator drug response and fractional exhaled nitric oxide is understudied. In this study, we identified DNA methylation markers associated with fractional exhaled nitric oxide in blood samples and bronchodilator drug response in pediatric asthma patients.
Article
Geriatrics & Gerontology
Hengjing Cui, Joshua D. Elford, Okko Alitalo, Paula Perez-Pardo, Janne Tampio, Kristiina M. Huttunen, Aletta Kraneveld, Markus M. Forsberg, Timo T. Myohanen, Aaro J. Jalkanen
Summary: Increasing evidence suggests that the gut-brain axis plays a crucial role in Parkinson's disease (PD), and 6-OHDA-induced nigrostriatal dopaminergic damage leads to increased α-synuclein (aSyn) levels and glial cell activation, particularly in the colon. This indicates that the gut-brain axis interactions in PD are bidirectional, and the detrimental process may start in the brain.
NEUROBIOLOGY OF AGING
(2023)
Article
Multidisciplinary Sciences
Carmina Angelica Perez-Romero, Lucero Mendoza-Maldonado, Alberto Tonda, Etienne Coz, Patrick Tabeling, Jessica Vanhomwegen, John MacSharry, Joanna Szafran, Lucina Bobadilla-Morales, Alfredo Corona-Rivera, Eric Claassen, Johan Garssen, Aletta D. Kraneveld, Alejandro Lopez-Rincon
Summary: As the COVID-19 pandemic calms down, there is growing concern about the possibility of future pandemics. The ability to quickly and accurately detect virus variants is crucial in mitigating the spread. Using an automated pipeline based on evolutionary algorithms, researchers have developed highly specific molecular tests for the main SARS-CoV-2 lineage and its variants. Preliminary validation shows promising results.
SCIENTIFIC REPORTS
(2023)
Proceedings Paper
Computer Science, Artificial Intelligence
Nisrine Mouhrim, Alberto Tonda, Itzel Rodriguez-Guerra, Aletta D. Kraneveld, Alejandro Lopez Rincon
Summary: This work proposes the use of an advanced evolutionary algorithm to set discretization thresholds for gene expression profiles. By using feedback from a classifier, the algorithm aims to maximize prediction accuracy while minimizing the number of different profiles obtained. The methodology is applied to a dataset of COVID-19 patients, demonstrating that the evolutionary approach outperforms traditional statistical analysis-based discretization and preserves the sense-making necessary for practitioners to trust the results.
PROCEEDINGS OF THE 2022 GENETIC AND EVOLUTIONARY COMPUTATION CONFERENCE COMPANION, GECCO 2022
(2022)