Neuroplasticity and Neurotrophic Factors Eero Castrén Laboratory

Eero

Neuronal plasticity is a fundamental process in neuronal development and recovery from brain disorders. The Trophin lab focuses on the role of neurotrophic factors, particularly Brain-Derived Neurotrophic Factor (BDNF) and its receptor TRKB, in the plasticity of the adult brain and in the mechanisms of action of drugs used for the treatment of brain disorders. Our particular focus has been on the mechanism of antidepressant drug action. We have discovered that antidepressant drugs, including typical and fast-acting antidepressants, directly bind to TRKB receptors and allosterically promote BDNF signaling. TRKB signaling in turn induces critical period-like plasticity that leads to beneficial rewiring of neuronal networks when antidepressant-induced plasticity is combined with training that guides plastic networks.

The Trophin lab is currently investigating details of the mechanisms of how antidepressants and other compounds activate BDNF signaling using advanced microscopy (both in vitro in cultured neurons and in vivo in mouse brain), biochemistry, molecular modeling, and structural studies. To reveal how TRKB signaling promotes the plasticity of neuronal networks, we are using optically activated TRKB (optoTRKB), in vivo imaging, single-cell transcriptomic, and electrophysiology. We are also pursuing behavioral models where neuronal activity is stimulated to guide drug-induced plasticity.

Our work has revealed a completely new mechanism of antidepressant drug action which links molecular drug effects directly to brain plasticity, suggesting new strategies for more effective treatment.  Mechanisms of neuronal plasticity are also highly pertinent to the recovery from other brain disorders, such as neurodegeneration and trauma.

 

Lab members

 

Umemori, Juzoh

Juzoh Umemori

Senior Researcher

    Current projects:
  • Network and gene expression analysis on pharmacological and optogenetically induced plasticity in mouse adult brain
  • Single nuclei and epigenetic analysis on neural plasticity especially in interneurons
    About:
    I obtained a Ph.D. (genetics) at the National Institute of Genetics (Japan) by studying behavioral genetics focusing on spontaneous locomotor activity. In the 1st postdoc in the same institute, I was studying genetics and epigenetics on mouse models of neurological disease. Then I was working at Fujita Health University (Japan) as a research associate, to study mouse models of psychiatric disease. Currently, I’m interested in network and gene expression level of neural plasticity, and mainly use the optoTrkB system, which can optically induce neural plasticity in temporal and spatial manners.

 

 

 

Casarotto, Plinio

Plinio Casarotto

Senior Researcher

    Current projects:
  • Mechanisms of drug-induced plasticity
  • Transactivation of NTRK2 receptors by GPCR: AGTR1/2 and CB1
    About:
    Graduated in Pharmacy and Biochemistry, followed by a Master’s degree in Pharmacology from the Federal University of Paraná, in Brazil, investigating the interaction between glucocorticoids and BDNF in models predictive of antidepressant effect. He obtained his Ph.D. in Pharmacology from the University of São Paulo, studying the involvement of BDNF/NTRK2 in the panicolytic-like effect of antidepressant drugs. Following a visiting period when he investigated the interaction between cannabinoid receptor 1 and NTRK2, he joined the Trophies Lab in 2015, to investigate the mechanisms of remodeling the NTRK2-associated proteins by antidepressant drugs and the molecular mechanisms behind the drug-induced activation of NTRK2. PC offers a course about the process of scientific publication to Master and Ph.D. students, and he is also the founding editor of a scientific journal dedicated to publishing results of replication attempts in neuroscience.

 

 

 

Priyadarshini, Madhusmita

Madhusmita Priyadarshini

Senior Researcher

    Current projects:
  • Neurotrophin and neurotransmitter interaction in antidepressant mechanism of action. Ntrk2 interaction with neurotransmitters serotonin and dopamine
  • Effects of environmental enrichment on transcriptional regulation of the BDNF and Ntrk2
    About:
    I completed my Ph.D. at the Faculty of Medicine, the University of Helsinki studying Parkinson´s disease using zebrafish as an animal model. During my post-doc, I got interested in translational neuroscience and joined the Trophins lab. I am currently working on the interaction of neurotrophin with the transmitters and trying to understand their synergistic roles in neuronal plasticity. I am also interested in understanding how environmental interaction affects these systems at a molecular level.

 

 

 

Biojone, Caroline

Caroline Biojone

Senior Researcher

    Current projects:
  • Modulation of TRKB signaling by nitric oxide and its role in plasticity
  • Involvement of TRKB dephosphorylation by PNN-PTPRS complex in plasticity restrain
    About:
    I graduated in Biological Sciences at Federal University of Alfenas, Brazil; and got an MSc and Ph.D. degree at the University of Sao Paulo, Brazil, focused on Neuropsychopharmacology. During my master's and Ph.D., I investigated the role of nitric oxide and TRKB signaling in behavioral models of stress. My interest in better understanding the connection between nitric oxide and TRKB signaling, at the cellular and molecular level, drove me to join the Trophin´s Lab as a post-doctoral researcher. Currently, I am working on understanding molecular mechanisms restraining TRKB activation and neuronal plasticity, such as its dephosphorylation by PNN-PTPRS complex, and nitration. I am proactive towards actions aiming at making science more inclusive and accessible - I am a member of the Woman in Life Sciences organization and co-founding editor at a free-to-read/free-to-publish Journal of Reproducibility in Neuroscience. I regularly contribute to Kolibri Festival by organizing playful scientific workshops for children; I am passionate about the idea of science communication for children as I believe that, in the long run, it can be a powerful weapon to ensure critical thinking and well-informed choices.

 

 

 

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Cecilia Brunello

Senior Researcher

    Current projects:
  • Screening of lipid-induced TrkB activation and plasticity
  • Molecular mechanisms of the interaction between TrkB and steroid hormones
  • Investigation of the role of BDNF/TrkB in the early development of Huntington´s disease
    About:
    I completed my bachelor's and master´s degrees in biology and neuroscience in Italy at the University of Padua and the University of Trieste. I obtained my Ph.D. in 2018 from the University of Helsinki. During my doctoral studies, I investigated the molecular mechanisms of tau protein-mediated pathology in order to better understand the development and progression of different neurodegenerative diseases. I join the Trophins lab in 2019 to investigate the effect of different lipids and hormones on TrkB activation and their role in promoting neural plasticity. In parallel, I am interested in understanding the role of the BDNF/TrkB axis in the etiology of neurodegenerative disorders, in particular Huntington´s disease.

 

 

 

Balin, Raz

Raz Balin

Doctoral Student

    Current projects:
  • Antidepressants influence neuro-circuits in the visual cortex and sensorial habituation.
  • Optogenetically localized induction of neuroplasticity in awake behaving animals
  • Effects of interneuron plasticity modulation on the social ability of rodents and correlative changes to the electrophysiological properties of rodent dmPFC area
    About:
    My background is in psychology, having acquired my baccalaureate in social science at Tel-Aviv University, and subsequently studied a master degree in Pisa University, specializing in educational psychology of learning disabilities.

    My fascination with the brain led me to pursue a career in brain research, starting in Pablo Blinder lab in Tel-Aviv university- where I have acquired my specialization in awake in-vivo rodent and behavioral experiments in combination with multi-photon microscopy.

 

 

 

Lesnikova, Angelina

Angelina Lesnikova

Doctoral Student

    Current projects:
  • Plasticity induced by pharmacological interventions
  • Genetically engineered juvenile-like plasticity in the adult brain
    About:
    I did my Master’s research at the Russian Academy of Sciences and received my Master’s degree from St. Petersburg State University.

 

 

 

Fred, Senem Merve

Merve Senem-Fred

Doctoral Student

    Current projects:
  • Antidepressant drug-induced plasticity in the brain
  • Proteins and membrane lipid content underlying the action of slow- and rapid-acting antidepressant drugs
    About:
    I obtained my B.Sc. degree in Molecular Biology and Genetics from Istanbul Technical University, Turkey, in 2013. During my bachelor studies, I also attended Umeå University in Sweden as part of the ERASMUS exchange program to study Molecular Biology for a year. Afterward, I moved to Finland to pursue my M.Sc. studies in Physiology and Neuroscience at the University of Helsinki. I became a member of Prof. Eero Castén’s team for my master thesis project, and I am currently working in the same laboratory to obtain my Ph.D. degree. My research focuses on understanding changes in the protein coupling/uncoupling to the TRKB receptor complex induced by slow- and rapid-acting antidepressant drugs. For this purpose, I use a combination of biochemical and behavioral methods.

 

 

 

Cannarozzo, Cecilia

Cecilia Cannarozzo

Doctoral Student

    Current projects:
  • Induction of visual cortex plasticity with pharmacological and non-pharmacological interventions
  • Role of a cholesterol-recognition motif (CARC) in the transmembrane region of TRKB in antidepressant-induced plasticity
    About:
    I obtained my B.Sc. in Biology and my M.Sc. in Neuroscience at the University of Trieste (Italy). During the Master I was awarded an Erasmus+ Scholarship to study at the University of Helsinki (Finland) for one semester, followed by an Erasmus Traineeship to work on my thesis in the Trophins laboratory of Prof. Eero Castrén. During my traineeship, I focused on studying the induction of plasticity in the visual cortex of mice by antidepressants and was captivated by the topic. I am currently working in the Trophins lab to obtain my Ph.D., broadening my research on visual cortex plasticity induced by pharmacological and non-pharmacological interventions. I am also interested in understanding the role of a cholesterol-recognition motif identified in the transmembrane region of TRKB in drug-induced plasticity by using in vitro and in vivo methods, such as molecular biology and confocal imaging techniques, behavioral analyses, and optical imaging.

 

 

 

 

Moliner, Rafael

Rafael Moliner

Doctoral Student

    Current projects:
  • Psychedelics and neuroplasticity: molecular and cellular mechanisms underlying the long-term effects of LSD
  • Induction of juvenile-like plasticity in the adult brain with fast-acting antidepressants
  • Membrane compartmentalization and receptor clustering dynamics of TrkB
    About:
    I studied Biochemistry at the Autonomous University of Barcelona (Spain) and graduated in Neuroscience at the University of Helsinki. I also developed research projects at the Netherlands Institute for Neuroscience in Amsterdam (Netherlands), the University of Oulu (Finland), and the Mediterranean Institute of Neurobiology in Marseille (France). My main scientific passion lies in exploring novel neuropharmacological strategies to treat psychiatric and neurodegenerative disorders, particularly those that involve neuronal plasticity and neurotrophic factors like BDNF and its receptor TrkB. With that purpose, I have focused my research on unveiling the mechanisms of action of drugs that trigger juvenile-like plasticity in the adult brain, like the selective serotonin reuptake inhibitor fluoxetine and the rapid-acting antidepressant ketamine. I am currently a Ph.D. candidate investigating the molecular and cellular mechanisms behind the long-term effects of psychedelics.

 

 

 

Didio, Giuliano

Giuliano Didio

Doctoral Student

    Current projects:
  • Optogenetic activation of neural plasticity
  • Role of inhibitory neurons in network plasticity
  • Behavioral flexibility in animal models (currently cocaine-induced reward-seeking behavior)
    About:
    I obtained my Bachelor’s degree in Biology at the University of Parma with an internship project in cancer biology. In 2017 I obtained an international Master’s degree in Neuroscience at the University of Trieste. I spent the last year of my Master’s studies during an internship here at the Trophin lab under Prof. Castrén’s and Dr. Umemori’s supervision, working on the assessment of an optogenetic system to control neural plasticity. After graduating, I came back a few months later to start my Ph.D. Although my academic interests wander from Autism to consciousness, at the moment my research activity focuses on using optogenetic plasticity to study the role of somatostatin inhibitory neurons in the control of neural network plasticity.

 

 

 

Kaurinkoski, Katja

Katja Kaurinkoski

Master's Student

    Current projects:
  • Effects of environmental enrichment on transcriptional regulation of BDNF and Ntrk2
  • Neurotrophins and neurotransmitter interaction in the antidepressant mechanism of action. Ntrk2 interaction with neurotransmitters serotonin and dopamine
    About:
    I completed my Bachelor in Biological Sciences at the University of Leicester in the UK in 2017. During my Bachelor I worked in the university's Phage lab, investigating the interaction between bacteriophages and bacterial vesicles. I started my Master's in Neuroscience at the University of Helsinki in 2018. I conducted practical training in the Medical Nutrition Physiology group studying the effects of short-chain fatty acids on the gut-brain axis, and I am now completing my Master’s thesis in the Trophin lab. For my Master’s thesis, I am investigating the effects of environmental enrichment on the transcriptional regulation of BDNF and Ntrk2. I am also passionate about Science Communication; I am an active member of The Science Basement ry, where I contribute to the podcast, help coordinate our social media, and was one of the organizers for the March for Science Helsinki 2019.

 

 

 

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Mikko Voipoi

Master's Student

    Current projects:
  • .
    About:
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Seiffert, Nina

Nina Seiffert

Master's Student

    Current projects:
  • Interaction of lipid compounds with TrkB and their effect on TrkB dimerization
    About:
    I obtained a Bachelor's Degree in Cognitive Science at the University of Osnabrück, Germany, in 2019. During my Bachelor studies, I went on an exchange as part of an Erasmus+ placement to study psychology for one semester at the University of Helsinki. Since August 2019 I am studying in the Neuroscience and Physiology Master's Program at the University of Helsinki. During my Master's studies I started a traineeship at the Trophin Lab and am currently continuing my work at the lab in form of my Master's thesis. As part of my thesis work, I am researching the interaction of different lipid compounds with TrkB and the effects of these compounds on TrkB dimerization.

 

 

 

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Elias Jetsonen

Bachelor Student

    Current projects:
  • .
    About:
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Kolehmainen, Sulo

Sulo Kolehmainen

Lab manager, Lab Technician

    Current projects:
  • Upkeep of several lab functions and ordering of supplies
  • Familiarizing students in working safely in a lab environment
  • Assisting in carrying out the experiments, translation of texts, basic scripts and any computer related problems
  • Person responsible of the NC Virus room
    About:
    Sulo got his bachelor's in laboratory sciences at the Metropolia University of Applied Sciences. On the way to graduation, he did his internship in the Trophins lab and has decided to stick around ever since. His common functions include instructing new (and old) students in good laboratory practices and safety, performing several upkeep tasks in the lab, and (almost) single-handedly genotyping all the mice that are to be used in breeding and experiments. He is usually there to help when technical issues arise, be it a broken electrophoresis chamber, mistreated pipette, malfunctioning coffee machine, or a computer gone haywire.

 

 

 

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Seija Lågas

Lab Technician

    Current projects:
  • Research technician in the groups of Eero Castren, Claudio Rivera and Heikki Rauvala
  • Takes care of the Neuronal Cell Culture Unit, which produces primary neurons for NC research groups as well as external research groups
  • Maintains cell lines and the introduction of students and new employees to cell culturing(primary and mammalian cell lines) and making genotyping
    About:
    I graduated as a laboratory technician in 1984 and have since worked in various laboratories. My work became more interesting when I came to the Institute of Biotechnology at the University with Heikki Rauvala's group in 1994. I automatically joined the Neuroscience Research Center in 2003 with Heikki Rauvala's group. During this time, I got to work with numerous different researchers, helping with dissertations. My experience is mainly with protein chemistry, cell culture, and antibody purification, orders, and ancillary laboratory work. Currently, I work with three different groups and manage NT’s Primary Cell Culture unit. I am also responsible for many general things at NT so if you need anything then get in touch.

 

 

Contact

Eero Castrén, Academy Professor
P.O. Box 63, FI-00014 University of Helsinki
Phone: +358 50 5207974
Email: eero.castren@helsinki.fi