Projects per year
Organization profile
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.
Fields of Science
- 3112 Neurosciences
- 1184 Genetics, developmental biology, physiology
International and National Collaboration
Profiles
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Maija Castrén, Senior Researcher
- Department of Physiology - Docent, Senior Researcher
- Faculty Common Matters (Faculty of Medicine) - Title of Docent
- Medicum - Principal Investigator
- NeuroDevDiseaseModelling
- Doctoral Programme Brain & Mind - Supervisor for doctoral programme
Person: U3 Research and teaching staff, UH , Teaching and research personnel
Projects
- 1 Finished
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NeuroASD: Activity dependent defects of Neuronal specification and circuit formation in Autism Spectrum Disorders
01/02/2018 → 31/03/2018
Project: Other project
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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. (eds.). 2. uud. p. ed. Helsinki: Kustannusosakeyhtiö Duodecim, p. 295-319 25 p.Translated title of the contribution :Clinical Neuropsychiatry; Autism spectrum disorder Research output: Chapter in Book/Report/Conference proceeding › Chapter › Professional
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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, In: Brain Sciences. 11, 2, 14 p., 209.Research output: Contribution to journal › Article › Scientific › peer-review
Open AccessFile -
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, In: Glia. 69, 12, p. 2947-2962 16 p.Research output: Contribution to journal › Article › Scientific › peer-review
Open AccessFile -
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 May 2020, In: Molecular Autism. 11, 1, 11 p., 41.Research output: Contribution to journal › Article › Scientific › peer-review
Open AccessFile -
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, In: Biological Psychiatry. 88, 6, p. 500-511 12 p.Research output: Contribution to journal › Article › Scientific › peer-review
Activities
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The 34th ECNP Congress
Maija Castrén (Speaker)
4 Oct 2021Activity: Talk or presentation types › Invited talk
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Childhood-onset genetic white matter disorders of the brain in Northern Finland
Maija Castrén (Pre-examiner)
May 2021Activity: Examination types › Pre-examiner of doctoral thesis
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Expert Evaluator for Marie Sklodowska-Curie Actions Posdoctoral Felloships programme
Maija Castrén (Consultant)
2021Activity: Consultancy types › Consultancy
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Generation of the Human Pluripotent Stem-Cell-Derived Astrocyte Model with Forebrain Identity
Maija Castrén (Supervisor)
2021Activity: Examination types › Supervision of other thesis (Master's, Licentiate)
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Increased iron content in the heart of the Fmr1 knockout mouse
Maija Castrén (Supervisor)
2021Activity: Examination types › Supervision of other thesis (Master's, Licentiate)
Press/Media
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Autismin kirjolla - monimuotoisia häiriöitä, kehityksellisiä ongelmia, mutta myös erityislahjakkuutta
07/05/2019
1 item of Media coverage
Press/Media: Press / Media