Work

Innovative Splice Switching Oligonucleotide Therapy for Niemann-pick Type C1 Disease

Year: 2023

Type: article

Abstract: Neural stem cells (NSCs) populating the subventricular zone (SVZ) of the lateral ventricles sustain one of the main processes of neurogenesis in the adult mammalian brain.Although these cells are pre-specified since embryonic ages, they remain quiescent during long periods until they reactivate giving rise to different olfactorybulb interneurons throughout life.Multiple mechanisms are involved in the correct regulation of the transition between quiescent and activated states of NSCs.Some of these mechanisms are associated with signals received from the environment or their neighboring cells via cell adhesion molecules (CAMs).Previous studies of our group reported an expansion of embryonic cortical progenitors after the conditional deletion of a CAM, Cadherin-2 (Cdh2), or a protein involved in its recruitment, Afadin, from the dorsal telencephalon.The proliferative defects produce hyperplasia and double cortex formation, due to the cell autonomous and noncell autonomous alterations in both models.However, while it is known the role in corticogenesis of Cdh2 and Afadin, only Cdh2 has been described as relevant in adult neurogenesis.In the present work, we describe the consequences of the perturbation of Afadin since early development in the adult neurogenic niche of SVZ.Besides the evident changes in the architecture of SVZ and in the rostral migratory stream (RMS), our results show increase of proliferation and neurogenic production, suggesting a possible function of afadin in the maintenance of the homeostasis of adult neurogenesis.

Source: IBRO Neuroscience Reports

DOI: 10.1016/j.ibneur.2023.08.121