Neonatal loss of FGFR2 in astroglial cells affects locomotion, sociability, working memory, and glia-neuron interactions in mice.

Autor: Stevens HE; Child Study Center, Yale School of Medicine, New Haven, CT, 06520, USA. hanna-stevens@uiowa.edu.; Department of Psychiatry, Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA, 52246, USA. hanna-stevens@uiowa.edu., Scuderi S; Child Study Center, Yale School of Medicine, New Haven, CT, 06520, USA., Collica SC; Child Study Center, Yale School of Medicine, New Haven, CT, 06520, USA., Tomasi S; Child Study Center, Yale School of Medicine, New Haven, CT, 06520, USA., Horvath TL; Department of Neuroscience, Yale University, New Haven, CT, 06520, USA.; Department of Comparative Medicine, Department of Obstetrics and Gynecology, Yale School of Medicine, New Haven, CT, 06520, USA., Vaccarino FM; Child Study Center, Yale School of Medicine, New Haven, CT, 06520, USA.; Department of Neuroscience, Yale University, New Haven, CT, 06520, USA.
Jazyk: angličtina
Zdroj: Translational psychiatry [Transl Psychiatry] 2023 Mar 11; Vol. 13 (1), pp. 89. Date of Electronic Publication: 2023 Mar 11.
DOI: 10.1038/s41398-023-02372-y
Abstrakt: Fibroblast growth factor receptor 2 (FGFR2) is almost exclusively expressed in glial cells in postnatal mouse brain, but its impact in glia for brain behavioral functioning is poorly understood. We compared behavioral effects from FGFR2 loss in both neurons and astroglial cells and from FGFR2 loss in astroglial cells by using either the pluripotent progenitor-driven hGFAP-cre or the tamoxifen-inducible astrocyte-driven GFAP-creER T2 in Fgfr2 floxed mice. When FGFR2 was eliminated in embryonic pluripotent precursors or in early postnatal astroglia, mice were hyperactive, and had small changes in working memory, sociability, and anxiety-like behavior. In contrast, FGFR2 loss in astrocytes starting at 8 weeks of age resulted only in reduced anxiety-like behavior. Therefore, early postnatal loss of FGFR2 in astroglia is critical for broad behavioral dysregulation. Neurobiological assessments demonstrated that astrocyte-neuron membrane contact was reduced and glial glutamine synthetase expression increased only by early postnatal FGFR2 loss. We conclude that altered astroglial cell function dependent on FGFR2 in the early postnatal period may result in impaired synaptic development and behavioral regulation, modeling childhood behavioral deficits like attention deficit hyperactivity disorder (ADHD).
(© 2023. The Author(s).)
Databáze: MEDLINE
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