1471-2202-8-26.pdf (1.8 MB)
Intracerebroventricular antisense knockdown of Gα[subscript i2] results in ciliary stasis and ventricular dilatation in the rat
journal contribution
posted on 2007-06-22, 12:35 authored by Kati S. Mönkkönen, Juhana M. Hakumäki, Robert A. Hirst, Riitta A. Miettinen, Christopher L. O'Callaghan, Pekka T. Männistö, Jarmo T. LaitinenBackground: In the CNS, the heterotrimeric G protein Gαi2 is a minor Gα subunit with restricted localization in the ventricular regions including the ependymal cilia. The localization of Gαi2 is conserved in cilia of different tissues, suggesting a particular role in ciliary function. Although studies with Gαi2-knockout mice have provided information on the role of this Gα subunit in peripheral tissues, its role in the CNS is largely unknown. We used intracerebroventricular (icv) antisense
administration to clarify the physiological role of Gαi2 in the ventricular system.
Results: High resolution MRI studies revealed that continuous icv-infusion of Gαi2-specific antisense oligonucleotide caused unilateral ventricular dilatation that was restricted to the antisense-receiving ventricle. Microscopic analysis demonstrated ependymal cell damage and loss
of ependymal cilia. Attenuation of Gαi2 in ependymal cells was confirmed by immunohistochemistry. Ciliary beat frequency measurements on cultured ependymal cells
indicated that antisense administration resulted in ciliary stasis.
Conclusion: Our results establish that Gαi2 has an essential regulatory role in ciliary function and CSF homeostasis.
History
Citation
BMC Neuroscience, 2007, 8 : 26Version
- VoR (Version of Record)