Peer-Reviewed Publication

Science China Press

image: 

Immunofluorescent images of S100β (red, ependymal cells) in the ependyma of Nestin–Cre and Rgs22f/f;Nestin–Cre mice at P21. By staining S100β, we assessed the integrity of LV wall in Rgs22f/f;Nestin–Cre mice. Compared to control mice (Nestin–Cre), a disrupted ependymal cell layer was observed in Rgs22 cKO mice. Photo credit: Xue Pang and Lin Gu.

Credit: Photo credit: Xue Pang and Lin Gu.

Hydrocephalus poses a significant threat to the pediatric population, with a prevalence of approximately 6 per 10,000 and a neonatal mortality rate of 13% pre-hospital discharge (Wright et al., 2016). Understanding the genetic and molecular mechanisms underlying hydrocephalus is critical for elucidating its pathogenesis and developing effective therapeutic strategies.

The scientists discovered that RGS22 is uniquely present in the brain’s ependymal cells, which line the ventricles and are crucial for cerebrospinal fluid flow. Experiments utilizing genetically modified mice lacking RGS22 in their nervous system revealed that these animals spontaneously developed severe hydrocephalus. This finding points to a critical function of RGS22 in the brain.

Delving into the cellular mechanisms, the study shows that without RGS22, ependymal cells are compromised, and their cilia, hair-like structures essential for fluid movement, are impaired. The researchers traced this back to an overactive response in the lysophosphatidic acid receptor (LPAR) signaling pathway. Notably, by blocking LPAR signaling, researchers were able to reduce hydrocephalus in RGS22-deficient rats, revealing a potential therapeutic approach.

This work not only advances our understanding of hydrocephalus but also suggests that targeting RGS22 could offer a novel strategy for diagnosis and treatment, bringing hope for the improvement of clinical outcomes in this challenging disease.

See the article:

RGS22 maintains the physiological function of ependymal cells to prevent hydrocephalus

https://doi.org/10.1007/s11427-024-2720-8