Background: Serotonin (5-hydroxytryptamin, 5-HT) is an indolamine platelet agonist, biochemically derived from tryptophan. 5-HT is secreted from the enterochromaffin cells into the gastrointestinal tract and blood. Blood 5-HT has been proposed to regulate hemostasis by acting as a vasoconstrictor and by triggering platelet signaling through 5-HT receptor 2A (5HTR2A). Although platelets do not synthetize 5-HT, they take 5-HT up from the blood and store it in their dense granules which are secreted upon platelet activation.
Objective: To identify the molecular composite of the 5-HT uptake system in platelets and elucidate the role of platelet released 5-HT in thrombosis and ischemic stroke.
Methods: 5-HT transporter knockout mice (5Htt-/-) were analyzed in different in vitro and in vivo assays and in a model of ischemic stroke.
Results: In 5Htt-/- platelets, 5-HT uptake from the blood was completely abolished and agonist-induced Ca2+ influx through store operated Ca2+ entry (SOCE), integrin activation, degranulation and aggregation responses to glycoprotein VI (GPVI) and C-type lectin-like receptor 2 (CLEC-2) were reduced. These observed in vitro defects in 5Htt-/- platelets could be normalized by the addition of exogenous 5-HT. Moreover, reduced 5-HT levels in the plasma, an increased bleeding time and the formation of unstable thrombi were observed ex vivo under flow and in vivo in the abdominal aorta and carotid artery of 5Htt-/- mice. Surprisingly, in the transient middle cerebral artery occlusion (tMCAO) model of ischemic stroke 5Htt-/- mice showed nearly normal infarct volume and the neurological outcome was comparable to control mice.
Conclusion: Although secreted platelet 5-HT does not appear to play a crucial role in the development of reperfusion injury after stroke, it is essential to amplify the second phase of platelet activation through SOCE and plays an important role in thrombus stabilization.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4723080 | PMC |
| http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0147664 | PLOS |
Publication Analysis
Top Keywords
Similar Publications
"Expectancy-Mood Neural Dynamics Predict Mechanisms of Short- and Long-Term Antidepressant Placebo Effects".
Biol Psychiatry Cogn Neurosci Neuroimaging
January 2025
Department of Psychiatry, University of Pittsburgh. Electronic address:
Objective: Acute experimental models of antidepressant placebo effects suggest that expectancies, encoded within the salience network (SN), are reinforced by sensory evidence and mood fluctuations. However, whether these dynamics extend to longer timescales remains unknown. To answer this question, we investigated how SN and default mode network (DMN) functional connectivity during the processing of antidepressant expectancies facilitates the shift from salience attribution to contextual cues in the SN to belief-induced mood responses in the DMN, both acutely and long-term.
View Article and Find Full Text PDFSubacute Symptoms of Depression and Anxiety in Stress-Exposed Mice: Role of Schinus terebinthifolia Raddi Leaf Lectin (SteLL).
J Ethnopharmacol
January 2025
Biochemistry Department, Center of Biosciences, Universidade Federal de Pernambuco, Recife, Brazil; Center for Therapeutic Innovation Suely Galdino (NUPIT-SG), Universidade Federal de Pernambuco, Recife, Brazil. Electronic address:
Ethnopharmacological Relevance: Anxiety and depression are leading causes of disability worldwide, often exacerbated by chronic stress. Schinus terebinthifolia Raddi. has been used in traditional medicine for several purposes.
View Article and Find Full Text PDFThe Primary Cilia are Associated with the Axon Initial Segment in Neurons.
Adv Sci (Weinh)
January 2025
State Key Laboratory of Membrane Biology, School of Life Sciences, Peking University, Beijing, 100871, China.
The primary cilia serve as pivotal mediators of environmental signals and play crucial roles in neuronal responses. Disruption of ciliary function has been implicated in neuronal circuit disorders and aberrant neuronal excitability. However, the precise mechanisms remain elusive.
View Article and Find Full Text PDFManaging depression in the elderly: real-world clinical considerations and perspectives.
Int Clin Psychopharmacol
January 2025
Department of Affective Disorders, Jagiellonian University Medical College; Kopernika 21a, 31-501 Kraków, Poland.
This study aims to elucidate current trends in clinical practice for managing depression in elderly patients, focusing on the utilization of pharmacotherapeutics and integrated care models to improve patient outcomes. A comprehensive survey was conducted among physicians from various European countries to gather insights into prescribing habits, treatment patterns, and the impact of comorbidities on therapeutic choices, with a focus on trazodone. The participants included psychiatrists, general practitioners, and neurologists actively involved in elderly depression care.
View Article and Find Full Text PDFThere is growing interest to investigate classic psychedelics as potential therapeutics for mental illnesses. Previous studies have demonstrated that one dose of psilocybin leads to persisting neural and behavioral changes. The durability of psilocybin's effects suggests that there are likely alterations of gene expression at the transcriptional level.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!