Publikationsdatenbank

Infect Neurodev - Human stem cell-derived neurospheres to explore the consequences of Listeria infection on brain development (2024)

Art

Vortrag

Autoren

Fischer, Annika (WE 14)

Lemke, Christine (WE 7)

van Vorst, Kira (WE 7)

Haiber, Lisa Maria

Fulde, Marcus (WE 7)

Bröer, Sonja (WE 14)

Seeger, Bettina

Kongress

VZET – Internes Symposium 2024

Hannover, 11.06.2024

Quelle

Virtuelles Zentrum für Ersatz- und Ergänzungsmethoden zum Tierversuch (VZET) - Internes Symposium 2024 — Stiftung Tierärztliche Hochschule Hannover (Hrsg.)

Hannover, 2024 — S. 6

Verweise

URL (Volltext): https://www.tiho-hannover.de/fileadmin/01_Verwaltung/Pressestelle/Termine/240529_VZET_int_Symp_2024_Programm.pdf

Kontakt

Institut für Pharmakologie und Toxikologie

Koserstr. 20
14195 Berlin
+49 30 838 53221
pharmakologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

Zoonotic infections during pregnancy can result in infection of the central nervous system (CNS) in surviving offspring. Neurodevelopmental disorders have been described as long-term consequences of pre- and perinatal CNS infections, however the underlying mechanisms are not well understood.
The objective of this study is to test the suitability of human induced pluripotent stem cell (iPSC)-derived neurospheres as a model to study the consequences of fetal CNS infections. The neurospheres will be used to mimic the human developing brain. The neurospheres comprise neural stem cells (NSCs) that differentiate into various neural and glial subtypes, including mature neural cell populations. The initial studies will focus on infection with Listeria monocytogenes, a bacterial pathogen that is known to cause lasting neurological impairments in infected offspring. The bacteria are transferred from the mother to the fetus primarily via the bloodstream, as the pregnant woman ingests contaminated food.
It is hypothesised that infection induces primary NSC depletion and accelerated maturation of surviving NSCs, leading to impaired differentiation, aberrant migration, and altered network activity. In a preliminary step, sufficient numbers of consistent neurospheres had to be generated, which are currently characterised via RT-qPCR and immunocytochemistry. The findings will be presented at the conference. Furthermore, cryopreservation protocols were employed to directly freeze neurospheres using two different cryopreservation media, with the objective of transferring them to biosafety level facilities for infection experiments. Preliminary results indicate that the recovery post-cryopreservation does not differ between the freezing media. However, the long-term cell survival rates do not show satisfactory results yet, necessitating the optimisation of the protocol. Next, initial infection experiments aim to identify an appropriate infection dose.

Acknowledgement: Funded by the German Federal Ministry of Education and Research (FKZ 01KI2311A/B).