NeuroDevDiseaseModelling

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.

Internationellt och inhemskt samarbete Publikationer och projekt inom de senaste fem åren.

Personer

Foto av Maija Castrén

Maija Castrén, Senior Researcher

Person: gästforskare, U3 Undervisnings- och forskningspersonal, HU, undervisnings- och forskningspersonal

19872020

Projekt

Publikationer

Astrocytes in Neuropathologies Affecting the Frontal Cortex

Peteri, U-K., Niukkanen, M. & Castren, M. L., 12 feb 2019, I : Frontiers in Cellular Neuroscience. 13, 9 s., 44.

Forskningsoutput: TidskriftsbidragÖversiktsartikelVetenskapligPeer review

Öppen tillgång
Fil

Autismikirjo: Tausta, diagnostiikka ja tutkimus

Timonen, T., Castren, M. & Ärölä-Dithapo, M., 2019, Jyväskylä: PS-kustannus. 381 s.

Forskningsoutput: Bok/rapportBok

Beneficial Effects of GLP-1 Agonist in a Male With Compulsive Food-Related Behavior Associated With Autism

Jarvinen, A., Laine, M. K., Tikkanen, R. & Castren, M. L., 1 mar 2019, I : Frontiers in psychiatry. 10, 5 s., 97.

Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

Öppen tillgång
Fil

Dysregulated Ca2+-Permeable AMPA Receptor Signaling in Neural Progenitors Modeling Fragile X Syndrome

Danesi, C. E., Keinänen, K. P. & Castren, M. L., 8 feb 2019, I : Frontiers in Synaptic Neuroscience. 11, 8 s., 2.

Forskningsoutput: TidskriftsbidragÖversiktsartikelVetenskapligPeer review

Öppen tillgång
Fil

Modeling FXS with mouse neural progenitors

Peteri, U-K. A. & Castren, M. L., 2019, Fragile-X Syndrome: Methods and Protocols. Ben-Yosef, D. & Mayshar, Y. (red.). New York, NY: Humana press, s. 71-78 8 s. (Methods in Molecular Biology; vol. 1942).

Forskningsoutput: Kapitel i bok/rapport/konferenshandlingKapitelVetenskapligPeer review

Aktiviteter

ISSCR 2019 Stem Cells & Organoids in Development & Disease

Ulla-Kaisa Anneli Peteri (Närvarande)
20 feb 201922 feb 2019

Aktivitet: Typer för deltagande i eller organisering av evenemangArrangemang av och deltagande i konferens/workshop/kurs/seminarium

Joint Meeting of the Finnish Developmental Biology Society & Finnish Stem Cell Network

Ulla-Kaisa Anneli Peteri (Närvarande)
26 okt 201827 okt 2018

Aktivitet: Typer för deltagande i eller organisering av evenemangArrangemang av och deltagande i konferens/workshop/kurs/seminarium

Molecular Mechanisms Involved in Altered Differentiation of Neural Progenitors in Fragile X Syndrome

Maija Castrén (Handledare)
27 feb 2018

Aktivitet: ExaminationstyperHandledare eller bihandledare av doktorsavhandling

Autism Seminar/Autismiseminaari;tiede ja yhteiskunta

Maija Castrén (Talare: Presentation)
11 sep 2018

Aktivitet: Typer för deltagande i eller organisering av evenemangArrangemang av och deltagande i konferens/workshop/kurs/seminarium

Tidningsurklipp