Browsing by Subject "Serotonin"

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  • Lindström, Mikael; Tohmola, Niina; Renkonen, Risto; Hämäläinen, Esa; Schalin-Jäntti, Camilla; Itkonen, Outi (2018)
    Background: Serotonin (5-hydroxytyramine) is a mediator of gastrointestinal smooth muscle contraction, and is secreted by neuroendocrine neoplasms (NENs). We developed a liquid chromatography tandem mass spectrometry (LC-MS/MS) assay for serum serotonin to be used in NEN diagnostics and follow-up. Methods: We used serum samples from healthy volunteers (n = 31) and patients suspected or monitored for NEN (n = 98). Serotonin-D-4 internal standard was added to samples before solid phase extraction (SPE) and quantification by LC-MS/MS. The effects of sample handling and preparation on serotonin stability were studied. Finally, we established a provisional reference range for serum serotonin and compared our assay with serum 5hydroxyindoleacetic acid (5-HIAA) for detection of NENs. Results: Our assay is sensitive and has a wide linear range (10-10,000 nmo1/1). Serum serotonin is stable for 7 days at room temperature and for 3 months at -20 degrees C. Sampling temperature is not critical. Normal range for serum serotonin was 270-1490 nmo1/1. We found that serum serotonin and 5-HIAA performed equally well as diagnostic tests for NENs. Conclusions: Our LC-MS/MS assay for serum serotonin is well suited for clinical research and patient diagnostics. Our results confirm that it can complement 5-HIAA in diagnosis of NENs.
  • Pazos Boubeta, Yago (Helsingin yliopisto, 2019)
    Neurotrophin, Brain-derived neurotrophic factor (BDNF) and its cognate receptor Tropomyosin receptor kinase B (TrkB), have been concomitantly linked with neuronal plasticity as well as antidepressant mechanism of action. Adult hippocampal neurogenesis involves proliferation and survival of new-born neurons and has been related to antidepressant mechanisms and cognitive improvement. Environmental enrichment (EE) enhances adult hippocampal neurogenesis (AHN) and induces anxiolytic-like effects. This study postulates that EE-living conditions could restore the abnormal serotonergic modulation on AHN of our transgenic mice. In this study, a transgenic mouse line wherein TrkB receptor is compromised from serotonergic neurons and AHN found to be impaired was used. To assess the behavioural effects and the changes in learning and memory tasks produced by 10-weeks of EE, a behavioural battery test was performed. Our results suggested anxiolytic-like effects from EE in the transgenic mice. Likewise, cognitive improvements were also observed in both control and transgenic mice promoted by EE. Moreover, hyperactivity observed in transgenic mice in standard conditions could be rescued, and no phenotypical differences were observed between control and transgenic mice subjected to EE. To further study the effects of EE on AHN, cellular proliferation and survival were studied through the incorporation of BrdU. The results indicate that the abnormal serotonergic regulation of AHN was rescued upon EE-living conditions. Moreover, molecular methods used to measure the alteration of gene expression revealed significant upregulation of genes related to neuronal plasticity and epigenetic modifications. Altogether, these results suggest EE promotes the neuronal plasticity, rescues the impaired regulation of AHN and modulates the genetic expression of the transgenic mice. Findings from this study could provide new insights regarding novel targets that could modulate adult brain plasticity.
  • Ylikoski, Ari; Partinen, Markku (2017)
    Unettomuuden lisääntyminen ja yöunen rikkonaisuus ovat tavallisia sekä ikääntymiseen että ¬neurodegeneraatioon liittyviä vaivoja. Ihmisen ikääntyessä useat välittäjäaineet vähenevät, kuten myös hermosolut erityisesti sinitumakkeessa ja hypotalamuksen tumakkeissa. Kohorttitutkimuksissa on havaittu, että unihäiriöt edeltävät usein neurodegeneratiivisten sairauksien tyypillisiä ydinoireita. Uuden tutkimustiedon mukaan unihäiriöt voivat altistaa neurodegeneratiivisille sairauksille ja pahentaa niitä. Unihäiriöt kuuluvat näiden sairauksien hoidettavissa oleviin riskitekijöihin. Uni tai sen puute saattavat suojata neurodegeneraatiolta tai altistaa sille usealla eri mekanismilla.
  • Hynninen, Elina; Moliner, Rafael; Ekelund, Jesper; Korpi, Esa R.; Elsilä, Lauri (2020)
    Psykedeelit eli serotonergiset hallusinogeenit ovat viime vuosikymmenen aikana keränneet yhä enemmän kiinnostusta neurobiologisessa ja psykiatrisessa tutkimuksessa. Psykedeeleillä on alustavan näytön perusteella positiivisia vaikutuksia masennuksen ja ahdistuksen sekä riippuvuuksien ja kivun hoidossa. Psykedeelien vaikutuksen tärkein molekulaarinen mekanismi on serotoniinireseptorin (5-HT2A-reseptorin) aktivointi. Subjektiivisesti koetut sekä hoidolliset vaikutukset välittynevät useita eri välittäjäaineita käyttävien hermoratojen toiminnallisten muutosten kautta. Näiden muutosten mekanismeja ei toistaiseksi tunneta. Psykedeelit muun muassa vähentävät aivojen tärkeiden yhteyskeskusten aktiivisuutta sekä mahdollisesti lisäävät hermosolujen muovautuvuutta.
  • Martti, Alvar (Helsingin yliopisto, 2019)
    Tausta: Alkoholismi on merkittävä kansanterveydellinen tauti, josta aiheutuu haittoja niin yksilölle kuin yhteiskunnallekin. Terapian ohella käytetty lääkehoito pohjautuu nykyään lähinnä opioidijärjestelmään ja alkoholin metaboliaan vaikuttaviin lääkkeisiin. Kuitenkin myös aivojen serotoniinijärjestelmän tiedetään osallistuvan riippuvuuden neurobiologisten mekansimien säätelyyn. Prekliinisen tiedon perusteella on kehitetty serotonergisia lääkkeitä, joiden on havaittu vähentävän alkoholin juomista kliinisissä tutkimuksissa. Myös psykedeeleihin kuuluvan lysergihapon dietyyliamiinin (LSD) vaikutukset aivoissa välittyvät pääasiassa serotoniinireseptoreiden kautta. 1960- ja 70-luvuilla tehtyjen kliinisten kokeiden perusteella LSD:n kerta-annos vähentää alkoholistien juomista pitkäaikaisesti, tehden siitä hyvin mielenkiintoisen lääkeainekandidaatin. LSD:n solubiologiset vaikutusmekanimsmit ovat kuitenkin vielä epäselvät, ja sen käyttöön liittyy paljon juridisia ongelmia. Tavoite: Tutkimuksen tavoitteena oli selvittää, ovatko hiiret sopivia eläinmalleja LSD:n pitkäaikaisten alkoholin kulutusta vähentävien vaikutusten tutkimiseen. Menetelmät: Kokeessa oli mukana 27 hiirtä, jotka totutettiin runsaaseen ja nopeaan alkoholin päivittäiseen kulutukseen Drinking in the Dark -menetelmän mukaisesti. Totuttamisen jälkeen hiiret jaettiin kolmeen ryhmään, joista kullekin annettiin joko suolaliuosta tai 50 tai 100 μg/kg LSD:tä intraperitoneaalisena injektiona. Injektioiden jälkeen alkoholin kulutusta seurattiin vielä viikon ajan. Tulokset: LSD:n kerta-annos vähensi hiirten etanolin juomista, mutta vain lyhyeksi ajaksi. Vaikutus ei kuitenkaan näyttänyt perustuvan hiirten juomishalukkuuden vähenemiseen, sillä veden kulutuksessa ei havaittu muutoksia. Johtopäätökset: Lyhyen ajan sisällä suureen alkoholin kulutukseen tottuneet hiiret eivät välttämättä ole sopivia eläinmalleja LSD:n pitkäaikaisten juomista vähentävien vaikutusten tutkimiseen.
  • Kraus, Christoph; Castrén, Eero; Kasper, Siegfried; Lanzenberger, Rupert (2017)
    Serotonin modulates neuroplasticity, especially during early life, and dysfunctions in both systems likewise contribute to pathophysiology of depression. Recent findings demonstrate that serotonin reuptake inhibitors trigger reactivation of juvenile-like neuroplasticity. How these findings translate to clinical antidepressant treatment in major depressive disorder remains unclear. With this review, we link preclinical with clinical work on serotonin and neuroplasticity to bring two pathophysiologic models in clinical depression closer together. Dysfunctional developmental plasticity impacts on later-life cognitive and emotional functions, changes of synaptic serotonin levels and receptor levels are coupled with altered synaptic plasticity and neurogenesis. Structural magnetic resonance imaging in patients reveals disease-state-specific reductions of gray matter, a marker of neuroplasticity, and reversibility upon selective serotonin reuptake inhibitor treatment. Translational evidence from magnetic resonance imaging in animals support that reduced densities and sizes of neurons and reduced hippocampal volumes in depressive patients could be attributable to changes of serotonergic neuroplasticity. Since ketamine, physical exercise or learning enhance neuroplasticity, combinatory paradigms with selective serotonin reuptake inhibitors could enhance clinical treatment of depression. (C) 2017 Elsevier Ltd. All rights reserved.
  • Majuri, Joonas; Joutsa, Juho; Johansson, Jarkko; Voon, Valerie; Parkkola, Riitta; Alho, Hannu; Arponen, Eveliina; Kaasinen, Valtteri (2017)
    Behavioral addictions, such as pathological gambling (PG) and binge eating disorder (BED), appear to be associated with specific changes in brain dopamine and opioid function, but the role of other neurotransmitter systems is less clear. Given the crucial role of serotonin in a number of psychiatric disorders, we aimed to compare brain serotonergic function among individuals with BED, PG and healthy controls. Seven BED patients, 13 PG patients and 16 healthy controls were scanned with high-resolution positron emission tomography (PET) using the serotonin transporter (SERT) tracer [C-11]MADAM. Both region-of-interest and voxel-wise whole brain analyses were performed. Patients with BED showed increased SERT binding in the parieto-occipital cortical regions compared to both PG and healthy controls, with parallel decreases in binding in the nucleus accumbens, inferior temporal gyrus and lateral orbitofrontal cortex. No differences between PG patients and controls were observed. None of the subjects were on SSRI medications at the time of imaging, and there were no differences in the level of depression between PG and BED patients. The results highlight differences in brain SERT binding between individuals with BED and PG and provide further evidence of different neurobiological underpinnings in behavioral addictions that are unrelated to the co-existing mood disorder. The results aid in the conceptualization of behavioral addictions by characterizing the underlying serotonin changes and provide a framework for additional studies to examine syndrome-specific pharmaceutical treatments. (C) 2017 Elsevier B.V. and ECNP. All rights reserved.
  • Sundvik, Maria; Puttonen, Henri; Semenova, Svetlana; Panula, Pertti (2021)
    We studied the social hierarchy in zebrafish and assessed differences in neurotransmitters and behavior in the F1 generation offspring of dominant and subordinate zebrafish (Danio rerio). We used behavioral assays to study locomotion, ability to complete cognitive tasks, social interaction and aggression. To study the neurochemical changes, we applied quantitative polymerase chain reaction, high pressure liquid chromatography and immunohistochemistry. Social hierarchies were formed both by males and females when animals were kept in same sex pairs in the dyadic dominant-subordinate hierarchy test. The offspring of dominant animals were the leaders in social interactions, however aggression in the mirror-test was not altered in any group. Serotonin and noradrenaline levels were lower in the F1 generation subordinate animals when compared with dominant animals, but not compared with animals that were naive to social hierarchy. The mRNA level of the rate-limiting enzyme in histamine synthesis, histidine decarboxylase, was significantly lower in dominant and subordinate larval zebrafish when compared with control animals. In the dominant adult zebrafish tyrosine hydroxylase 1 mRNA level was lower compared with control animals, whereas tyrosine hydroxylase 2 mRNA was not different. The result was verified with immunohistochemistry. There were gender specific differences between the dominant and subordinate animals, where the dominant females performed better in cognitive tasks such as the T-maze than subordinate females. This was not observed in males, as the behavior of the dominant and subordinate males did not differ. These results add to the understanding of the plastic nature of the central nervous system and show that neurochemical features in aminergic neurotransmitter systems are associated with social leadership and dominance.