Projekt per år
Organisationsprofil
Organisationsprofil
The research team investigates molecular mechanisms underlying neurodevelopmental disorders, especially mechanisms causing features requiring treatment such as challenging behavioural problems in fragile X syndrome (FXS) and autism related disorders. The ultimate goal is to develop improved treatment strategies for these disorders. The team uses patient-specific induced pluripotent stem cells (iPSCs) for disease modelling in dish. Studies explore alterations of functional responses in iPSC-derived neuronal cells in a cell type-dependent manner and explore contribution of astrocytes to impaired neuronal network function.
Previous work of the lab has functionally characterized differentiation of glutamate-responsive human and mouse neural progenitors and demonstrated aberrances during early stages of neuronal cell differentiation in FXS. The recently published studies revealed enhanced intracellular Ca2+ responses to AMPA receptor activation in neural progenitors differentiated from human iPSCs generated from somatic cells of FXS males compared to controls. Increased Ca2+-permeable AMPA receptor (CP-AMPAR) activity associates with increased Ca2+ influx via L-type voltage-gated calcium channels and augmented responses to membrane depolarization and to NMDA and type I metabotropic glutamate receptor activation. Changes of Ca2+ dynamics affect fate determination, differentiation, and migration of FXS neural progenitors. Increased Ca2+ influx through CP-AMPARs renders neural progenitors more susceptible to excitotoxicity. Increased vulnerability may act as a selective factor during cell differentiation and interfere with establishment of neocortical circuits leading to network hyperexcitability in FXS brain.
Vetenskapsgrenar
- 3112 Neurovetenskaper
- 1184 Genetik, utvecklingsbiologi, fysiologi
Samarbeten och ledande forskningsområden under de senaste fem åren
Profiler
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Maija Castrén, Senior Researcher
- Avdelningen för fysiologi - Docent, äldre forskare
- Fakultetens gemensamma (Medicinska fakulteten) - Titeln docent
- Medicum - Forskningsledare (Principal Investigator)
- NeuroDevDiseaseModelling
- Doctoral Programme in Integrative Life Science - Handledare för doktorandprogram
- Doctoral Programme Brain & Mind - Handledare för doktorandprogram
Person: U3 Undervisnings- och forskningspersonal, HU, undervisnings- och forskningspersonal
Projekt
- 1 Slutfört
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NeuroASD: Activity dependent defects of Neuronal specification and circuit formation in Autism Spectrum Disorders
Castrén, M. (Projektledare)
01/02/2018 → 31/03/2018
Projekt: Annan projekt
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Autismikirjon häiriöt
Castrén, M., Grönfors, S., Timonen, T. & Tani, P., 1 jan. 2021, Kliininen neuropsykiatria. Juva, K., Hublin, C., Kalska, H., Korkeila, J., Sainio, M. & Tani, P. (red.). 2. uud. p. red. Helsinki: Kustannusosakeyhtiö Duodecim, s. 295-319 25 s.Forskningsoutput: Kapitel i bok/rapport/konferenshandling › Kapitel › Professionell
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Generation of the Human Pluripotent Stem-Cell-Derived Astrocyte Model with Forebrain Identity
Peteri, U.-K., Pitkonen, J., Utami, K. H., Paavola, J., Roybon, L., Pouladi, M. A. & Castren, M. L., feb. 2021, I: Brain Sciences. 11, 2, 14 s., 209.Forskningsoutput: Tidskriftsbidrag › Artikel › Vetenskaplig › Peer review
Öppen tillgångFil -
Urokinase plasminogen activator mediates changes in human astrocytes modeling fragile X syndrome
Peteri, U.-K., Pitkonen, J., de Toma, I., Nieminen, O., Utami, K. H., Strandin, T. M., Corcoran, P., Roybon, L., Vaheri, A., Ethell, I., Casarotto, P., Pouladi, M. A. & Castren, M. L., dec. 2021, I: Glia. 69, 12, s. 2947-2962 16 s.Forskningsoutput: Tidskriftsbidrag › Artikel › Vetenskaplig › Peer review
Öppen tillgångFil -
Elevated de novo protein synthesis in FMRP-deficient human neurons and its correction by metformin treatment
Utami, K. H., Yusof, N. A. B. M., Kwa, J. E., Peteri, U.-K., Castrén, M. L. & Pouladi, M. A., 27 maj 2020, I: Molecular Autism. 11, 1, 11 s., 41.Forskningsoutput: Tidskriftsbidrag › Artikel › Vetenskaplig › Peer review
Öppen tillgångFil -
Integrative analysis identifies key molecular signatures underlying neurodevelopmental deficits in fragile X syndrome
Utami, K. H., Skotte, N. H., Colaco, A. R., Yusof, N. A. B. M., Sim, B., Yeo, X. Y., Bae, H.-G., Garcia-Miralles, M., Radulescu, C. I., Chen, Q., Chaldaiopoulou, G., Liany, H., Nama, S., Peteri, U.-K. A., Sampath, P., Castrén, M., Jung, S., Mann, M. & Pouladi, M., 15 sep. 2020, I: Biological Psychiatry. 88, 6, s. 500-511 12 s.Forskningsoutput: Tidskriftsbidrag › Artikel › Vetenskaplig › Peer review
Aktiviteter
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Uunituoreet autismikirjosta- katsaus nykytilanteeseen ja tulevaisuuteen
Castrén, M. (!!Speaker)
13 juni 2024Aktivitet: Typer för tal eller presentation › !!Oral presentation
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Expert Evaluator for Marie Sklodowska-Curie Actions Posdoctoral Felloships programme
Castrén, M. (!!Consultant)
2021Aktivitet: Konsulttyper › !!Consultancy
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The 34th ECNP Congress
Castrén, M. (!!Speaker)
4 okt. 2021Aktivitet: Typer för tal eller presentation › !!Invited talk
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Childhood-onset genetic white matter disorders of the brain in Northern Finland
Castrén, M. (Förhandsgranskare)
maj 2021Aktivitet: Examinationstyper › Förhandsgranskare av doktorsavhandling
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Kehitykselliset neuropsykiatriset sairaudet uuden tutkimustiedon valossa
Castrén, M. (!!Speaker)
10 sep. 2021Aktivitet: Typer för tal eller presentation › !!Invited talk
Tidningsurklipp
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Autismin kirjolla - monimuotoisia häiriöitä, kehityksellisiä ongelmia, mutta myös erityislahjakkuutta
07/05/2019
1 objekt av Mediabevakning
Press/media: !!Press / Media