Abstract
Presence of neural stem cells in adult mammalian brains, including human, has been clearly demonstrated by several studies. The functional significance of adult neurogenesis is slowly emerging as new data indicate the sensitivity of this event to several “every day” external stimuli such as physical activity, learning, enriched environment, aging, stress and drugs. In addition, neurogenesis appears to be instrumental for task performance involving complex cognitive functions. Despite the growing body of evidence on the functional significance of NSC and despite the bulk of data concerning the molecular and cellular properties of NSCs and their niches, several critical questions are still open. In this work we review the literature describing i) old and new sites where NSC niche have been found in the CNS; ii) the intrinsic factors regulating the NSC potential; iii) the extrinsic factors that form the niche microenvironment. Moreover, we analyse NSC niche activation in iv) physiological and v) pathological conditions. Given the not static nature of NSCs that continuously change phenotype in response to environmental clues, a unique “identity card” for NSC identification is still lacking. Moreover, the multiple location of NSC niches that increase in diseases, leaves open the question of whether and how these structures communicate throughout long distance. We propose a model where all the NSC niches in the CNS may be connected in a functional network using the threads of the meningeal net as tracks.
Highlights
The complex architecture of the adult brain is the product of genetic instruction, cellular cross-talk and interactions between the organism and the external world
We found that (i) nestin-positive cells were present in the leptomeningeal compartment at the embryonic stages and persisted up to adulthood, (ii) leptomeningeal nestin-positive cells could be extracted and cultured as neurospheres with features similar to the neural stem/progenitor cells (NSCs)-derived neurospheres, (iii) leptomeningeal nestin-positive cells could be cultured as adherent cells and expanded in vitro as homogeneous population of nestin-positive cells that highly express many of the stemness-related genes, (iv) expanded nestin-positive cells could be induced to differentiate in vitro with high efficiency to generate excitable neurons and (v) expanded cells differentiated into neurons when injected into brains of living rats
We used lentiviral transduction of meninges to show that meningeal nestin- and DCX-positive cells contribute to glial scar formation after spinal cord injury (SCI), giving a new insight into the complexity of the parenchymal reaction to a traumatic injury [167]. These findings indicate that meninges share common properties with classical NSC niches including the presence of cells with neural precursor features. The origin of these cells has not been determined yet; on the other hand, we showed that meninges can host heterologous NSCs injected into the ventriculum [Fumagalli G., Decimo I., Bifari F., Krampera M
Summary
The complex architecture of the adult brain is the product of genetic instruction, cellular cross-talk and interactions between the organism and the external world. Newborn neurons derive from less differentiated neural stem/progenitor cells (NSCs). Cell transplantation studies have demonstrated that, NSCs derived from spinal cord will differentiate into glial cells when implanted into the region of origin, they are able to give rise to neurons when heterotopically grafted into the neurogenic hippocampus [147].
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