Growth factor treatment promotes mobilization of young but not aged adult subventricular zone precursors in response to demyelination

Abstract

Precursor cells of the adult mouse subventricular zone (SVZ) are mobilized and recruited by a lysolecithin (LPC)-induced demyelination of the corpus callosum. Because age decreases the proliferation of the SVZ neural precursors as well as the potential for myelin repair of the adult central nervous system, we have compared the ability of young and aged adult neural precursors to respond to LPC-induced demyelination. With age, the SVZ cells lost their capacity to proliferate and to be recruited by the lesion. Whereas a single injection of fibroblast growth factor-2 or transforming growth factor-␣ stimulated the proliferation of SVZ and rostral migratory stream precursors in both groups of animals after demyelination, they favored recruitment at the lesion in young mice but not in aged ones. In vitro experiments using neurospheres derived from young and aged animals indicated that both populations have the same migratory performances. Our in vivo data thus suggest that aged neural precursors may loose their intrinsic capacities to respond to demyelination-induced signals. Alternatively, their function may be altered by modification of the aged extracellular environment.

Growth factor regulation of remyelination: behind the growing interest in endogenous cell repair of the CNS

“…Furthermore, MS lesions, especially those in the periventricular white matter, show evidence of progenitor cell activation in the SVZ and mobilization to lesion areas [44]. Thus, growth factors that promote recruitment of OP cells to lesions from the SVZ may enhance the repair response from endogenous cell populations, as has been reported from animal studies [5,42]. Proliferation of SVZ cells in the adult CNS can be stimulated by FGF2 and/or EGF [45,46].…”

“…However, analysis of remyelination can be complicated in EAE models because modulation of the growth factor or cytokine under study can also alter the immune response and disease severity [3,4]. Gliotoxin models, such as injection of lysolecithin or ethidium bromide or ingestion of cuprizone, can accomplish a relatively specific period of demyelination after which the demyelinating agent is no longer active [5][6][7]. Therefore, gliotoxin models circumvent the autoimmune complexity and provide a reproducible demyelination episode to simplify analysis of cellular responses associated with remyelination.…”

“…The viral transduction experiments increased FGF2 concentration in the cerebrospinal fluid, which could possibly allow FGF2 to act on different cell populations relative to the endogenous FGF2 availability. Indeed, FGF2 administration has been reported to increase recruitment of OP cells from the subventricular zone (SVZ) to nearby areas of demyelination in the corpus callosum [5].…”

“…These models show that OP cells are recruited into lesions from nearby normal appearing white matter [40,41]. In addition, SVZ cells can contribute to the repair of lesions in the adjacent corpus callosum [5,42]. Similarly, in some MS patients, white matter lesion areas can contain substantial populations of immature oligodendrocyte lineage cells and premyelinating oligodendrocytes [27,43].…”

The effect of triiodothyronine on maturation and differentiation of oligodendrocyte progenitor cells during remyelination following induced demyelination in male albino rat

“…Tsiperson et al (2015) also demonstrated that following demyelination by cuprizone, an increase in PDGFR␣ progenitors was observed in wild mice as a result of increased DNA synthesis and cell proliferation. According to Decker et al (2002), cytokines and growth factors released either from widespread inflammatory and glial cells (Levine, 1994) or from damaged axons after demyelination (Di Bello et al, 1999), induce OPCs to reenter the cell cycle after demyelination.…”