NeuroDevDiseaseModelling

Organization profile

Organisation 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.

International and National Collaboration Publications and projects within past five years.

Projects 2018 2018

Publications 2009 2019

Astrocytes in Neuropathologies Affecting the Frontal Cortex

Peteri, U-K., Niukkanen, M. & Castren, M. L., 12 Feb 2019, In : Frontiers in Cellular Neuroscience. 13, 9 p., 44.

Research output: Contribution to journalReview ArticleScientificpeer-review

Open Access
File

Autismikirjo. Tausta, diagnostiikka ja tutkimus

Translated title of the contribution: Autism. Background, Diagnostics and ResearchTimonen, T., Castren, M. L. & Ärölä-Dithapo, M., 2019

Research output: Book/ReportBookProfessional

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, In : Frontiers in psychiatry. 10, 5 p., 97.

Research output: Contribution to journalArticleScientificpeer-review

Open Access
File

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, In : Frontiers in Synaptic Neuroscience. 11, 8 p., 2.

Research output: Contribution to journalReview ArticleScientificpeer-review

Open Access
File

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. (eds.). Springer, (Methods in Molecular Biology; vol. 1942).

Research output: Chapter in Book/Report/Conference proceedingChapterScientificpeer-review

Activities 2006 2019

ISSCR 2019 Stem Cells & Organoids in Development & Disease

Ulla-Kaisa Anneli Peteri (Attendee)
20 Feb 201922 Feb 2019

Activity: Participating in or organising an event typesOrganisation and participation in conferences, workshops, courses, seminars

Jyväskylän yliopisto

Maija Castrén (Other role)
2018

Activity: Visiting an external institution typesAcademic visit to other institution

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

Ulla-Kaisa Anneli Peteri (Attendee)
26 Oct 201827 Oct 2018

Activity: Participating in or organising an event typesOrganisation and participation in conferences, workshops, courses, seminars

The 2nd Nordic PhD Summit

Ulla-Kaisa Anneli Peteri (Attendee)
24 Aug 201825 Aug 2018

Activity: Participating in or organising an event typesOrganisation and participation in conferences, workshops, courses, seminars

11th FENS Forum of Neuroscience, Berlin 2018

Ulla-Kaisa Anneli Peteri (Attendee)
7 Jul 201811 Jul 2018

Activity: Participating in or organising an event typesOrganisation and participation in conferences, workshops, courses, seminars