Exosomes as Novel Regulators of Adult Neurogenic Niches

Neurogenic niches in the adult mammalian brain. (A) Schematic representation of the neurogenic regions (niches) in a sagittal section of the adult mouse brain: the subgranular zone (SGZ, orange) in dentate gyrus (DG) of the hippocampus (Hip), and the subventricular zone (SVZ, red) in the lateral wall of the lateral ventricles (LV). SVZ-derived newborn neurons migrate towards the olfactory bulb (OB) through the rostral migratory stream (RMS). (B) Cellular components of neurogenic niches. In addition to the neural stem cell (NSC)-neuron lineage, neurogenic niches are composed of glial cells (astrocytes, microglia and ependymal cells) and vascular cells (endothelial cells, pericytes). (C,D) Illustration of SGZ and SVZ neurogenic niches. The cytoarchitecture and relationships between cellular components of the niche are represented. Different cell types (color and shape) correspond to those depicted in (B). Note the close proximity between blood vessels and NSCs/NPCs in both niches. (C) The SGZ neurogenic niche. Radial type 1 cells correspond to the NSCs that give rise to type 2a/b NPCs, which differentiate into type 3 neuroblasts. Neuroblasts migrate guided by astrocytes and become maturing neurons that finally mature and integrate into the granular cell layer (GCL). (D) SVZ neurogenic niche. This niche is located underneath the ependymal lining (E) of the LV. It is composed of type B quiescent cells (NSCs), which can activate and generate type C NPCs that rapidly proliferate and generate type A neuroblasts. Neuroblasts migrate long distances through the rostral migratory stream (RMS) to the OB where they mature into interneurons. Note that a tunnel of astrocytes and a scaffold of blood vessels guide migration of neuroblasts. Also note that monociliated type B cells can directly contact cerebrospinal fluid (CSF) and blood vessels. Ce, cerebelum; Cx, cortex; Str, striatum.

Adult neurogenesis has been convincingly demonstrated in two regions of the mammalian brain: the sub-granular zone (SGZ) of the dentate gyrus (DG) in the hippocampus, and the sub-ventricular zone (SVZ) of the lateral ventricles (LV). SGZ newborn neurons are destined to the granular cell layer (GCL) of the DG, while new neurons from the SVZ neurons migrate rostrally into the olfactory bulb (OB). The process of adult neurogenesis persists throughout life and is supported by a pool of neural stem cells (NSCs), which reside in a unique and specialized microenvironment known as “neurogenic niche”. Neurogenic niches are structured by a complex organization of different cell types, including the NSC-neuron lineage, glial cells and vascular cells. Thus, cell-to-cell communication plays a key role in the dynamic modulation of homeostasis and plasticity of the adult neurogenic process. Specific cell-cell contacts and extracellular signals originated locally provide the necessary support and regulate the balance between self-renewal and differentiation of NSCs. Furthermore, extracellular signals originated at distant locations, including other brain regions or systemic organs, may reach the niche through the cerebrospinal fluid (CSF) or the vasculature and influence its nature. The role of several secreted molecules, such as cytokines, growth factors, neurotransmitters, and hormones, in the biology of adult NSCs, has been systematically addressed. Interestingly, in addition to these well-recognized signals, a novel type of intercellular messengers has been identified recently: the extracellular vesicles (EVs). EVs, and particularly exosomes, are implicated in the transfer of mRNAs, microRNAs (miRNAs), proteins and lipids between cells and thus are able to modify the function of recipient cells. Exosomes appear to play a significant role in different stem cell niches such as the mesenchymal stem cell niche, cancer stem cell niche and pre-metastatic niche; however, their roles in adult neurogenic niches remain virtually unexplored. This review focuses on the current knowledge regarding the functional relationship between cellular and extracellular components of the adult SVZ and SGZ neurogenic niches, and the growing evidence that supports the potential role of exosomes in the physiology and pathology of adult neurogenesis.

Krishan Maggon 's insight:

REVIEW ARTICLE 

Front. Cell. Neurosci., 19 January 2016

Exosomes as Novel Regulators of Adult Neurogenic Niches 

Luis Federico Bátiz1,2,3*, Maite A. Castro1,2,4, Patricia V. Burgos1,2,5, Zahady D. Velásquez1,3, Rosa I. Muñoz1,3, Carlos A. Lafourcade6, Paulina Troncoso-Escudero1,4 and Ursula Wyneken6* 

1Center for Interdisciplinary Studies on the Nervous System (CISNe), Universidad Austral de Chile, Valdivia, Chile2Program for Cell Biology and Microscopy, Universidad Austral de Chile, Valdivia, Chile3Instituto de Anatomía, Histología y Patología, Facultad de Medicina, Universidad Austral de Chile, Valdivia, Chile4Instituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile5Instituto de Fisiología, Facultad de Medicina, Universidad Austral de Chile, Valdivia, Chile6Laboratorio de Neurociencias, Facultad de Medicina, Universidad de Los Andes, Santiago, Chile.http://journal.frontiersin.org/article/10.3389/fncel.2015.00501/full

 http://dx.doi.org/10.3389/fncel.2015.00501