Exosomes as Novel Regulators of Adult Neurogenic Niches

Abstract

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.

miR-450a-5p within rat adipose tissue exosome-like vesicles promotes adipogenic differentiation by targeting WISP2

“…These results indicate that Exo-AT contains adipogenic factors that could trigger adipogenic signaling in ADSCs, resulting in adipogenic differentiation. In fact, previous studies have proved that the exosomes derived from osteoblasts, neurons and muscle cells can mediate differentiation of MSCs, although no work had been undertaken on Exo-AT (Narayanan et al, 2016; Cui et al, 2016; Batiz et al, 2015;Choi et al, 2016). Therefore, we conclude that exosomes may serve as a mediator of communication between stem cells and mature tissue cells.…”

“…Although some functions or mechanisms remain elusive, it has been demonstrated that exosomes can modulate their neighboring cells by influencing major cellular process including apoptosis, cell differentiation, proliferation and metabolism (Qin et al, 2016;Braicu et al, 2014). One obvious point about the content of exosomes is that they contain miRNAs, which can inhibit translation of mRNAs by targeting 3′ untranslated regions (UTRs) (Batiz et al, 2015). Transported miRNAs are capable of targeting mRNAs in recipient cells and, hence, are associated with cell-to-cell signaling and communication (He et al, 2014;Valadi et al, 2007).…”

Feto-Maternal Trafficking of Exosomes in Murine Pregnancy Models

“…However, how these signals are communicated between the fetal and maternal compartments is poorly understood. As intercellular signaling vesicles that can travel long distances through tissues and fluids (Raposo and Stoorvogel, 2013; Mincheva-Nilsson and Baranov, 2014; Bátiz et al, 2015; De Toro et al, 2015), exosomes may be carriers of these signals.…”

“…Exosomes are characterized by their contents, which reflect the physiological status of the origin cell and can regulate the phenotype of the target cell (Kambe et al, 2014; Bátiz et al, 2015; Sheller et al, 2016; Willms et al, 2016). At term, oxidative stress and inflammation build up in the amniotic cavity, causing cellular senescence of the fetal membranes and subsequent release of signals of cellular damage (Menon, 2014; Behnia et al, 2015, 2016; Polettini et al, 2015; Menon et al, 2016b).…”

Molecular anatomy and functions of the choroidal blood-cerebrospinal fluid barrier in health and disease

“…These factors can reach distal areas of the brain via bulk flow of the CSF and can act in both an autocrine and paracrine manner [63,137]. In addition to diffusible factors, exosomes containing signaling factors and non-coding (nc) RNAs, such as long ncRNAs and miRNAs, are present in the CSF [11] and can be choroid plexus-derived [6,55]. Finally, the choroid plexuses also contain a large array of enzymes and act as an enzymatic or metabolic barrier, by modulating the activity and availability of neurotransmitters, peptides, growth factors, hormones, drugs and xenobiotics.…”