Publisher Correction: α-SNAP is expressed in mouse ovarian granulosa cells and plays a key role in folliculogenesis and female fertility.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Pericytes in Multiple Sclerosis.

Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease that affects the central nervous system (CNS), particularly, in young adults. Current MS treatments aim to reduce demyelination; however, these have limited efficacy, display side effects and lack of regenerative activities. Oligodendrocyte progenitor cells (OPCs) represents the major source for new myelin. Upon demyelination, OPCs get activated, proliferate, migrate towards the lesion, and differentiate into remyelinating oligodendrocytes. Although myelin repair (remyelination) represents a robust response to myelin damage, during MS, this regenerative phenomenon decays in efficiency or even fails. CNS-resident pericytes (CNS-PCs) are essential for vascular homeostasis regulating blood-brain barrier (BBB) permeability and stability as well as endothelial cells (ECs) function during angiogenesis and neovascularization. Recent studies indicate that CNS-PCs also play a crucial role regulating OPC function during remyelination, and very importantly, these cells are substantially affected in MS. This chapter summarizes important aspects of MS and CNS remyelination as well as it provides new insights supporting the contribution of CNS-PCs to myelin regeneration and to MS pathology. Currently, there is evidence arguing in favor of CNS-PCs as novel therapeutic targets for the development of future treatments for MS.

Pericytes Favor Oligodendrocyte Fate Choice in Adult Neural Stem Cells.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Upon demyelination, oligodendrocyte progenitor cells (OPCs) are activated and they proliferate, migrate and differentiate into myelin-producing oligodendrocytes. Besides OPCs, neural stem cells (NSCs) may respond to demyelination and generate oligodendrocytes. We have recently shown that CNS-resident pericytes (PCs) respond to demyelination, proliferate and secrete Laminin alpha2 (Lama2) that, in turn, enhances OPC differentiation. Here, we aimed to evaluate whether PCs influence the fate choice of NSCs in vitro, towards the production of new myelin-producing cells. Indeed, upon exposure to conditioned medium derived from PCs (PC-CM), the majority of NSCs gave rise to GalC- and myelin basic protein (MBP)-expressing oligodendrocytes at the expense of the generation of GFAP-positive astrocytes. Consistent with these findings, PC-CM induces an increase in the expression of the oligodendrocyte fate determinant Olig2, while the expression level of the astrocyte determinant ID2 is decreased. Finally, pre-incubation of PC-CM with an anti-Lama2 antibody prevented the generation of oligodendrocytes. Our findings indicate that PCs-derived Lama2 instructs NSCs to an oligodendrocyte fate choice favoring the generation of myelin-producing cells at the expense of astrocytes in vitro. Further studies aiming to reveal the role of PCs during remyelination may pave the way for the development of new therapies for the treatment of MS.

α-SNAP is expressed in mouse ovarian granulosa cells and plays a key role in folliculogenesis and female fertility.

The balance between ovarian folliculogenesis and follicular atresia is critical for female fertility and is strictly regulated by a complex network of neuroendocrine and intra-ovarian signals. Despite the numerous functions executed by granulosa cells (GCs) in ovarian physiology, the role of multifunctional proteins able to simultaneously coordinate/modulate several cellular pathways is unclear. Soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein (α-SNAP) is a multifunctional protein that participates in SNARE-mediated membrane fusion events. In addition, it regulates cell-to-cell adhesion, AMPK signaling, autophagy and apoptosis in different cell types. In this study we examined the expression pattern of α-SNAP in ovarian tissue and the consequences of α-SNAP (M105I) mutation (hyh mutation) in folliculogenesis and female fertility. Our results showed that α-SNAP protein is highly expressed in GCs and its expression is modulated by gonadotropin stimuli. On the other hand, α-SNAP-mutant mice show a reduction in α-SNAP protein levels. Moreover, increased apoptosis of GCs and follicular atresia, reduced ovulation rate, and a dramatic decline in fertility is observed in α-SNAP-mutant females. In conclusion, α-SNAP plays a critical role in the balance between follicular development and atresia. Consequently, a reduction in its expression/function (M105I mutation) causes early depletion of ovarian follicles and female subfertility.