The discovery of precursor cells and neurogenesis in postnatal dorsal root sensory ganglia
Namaka, Michael Peter
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Neurogenesis is known to continue in various regions of the central nervous system (CNS) throughout life. However, it is currently unknown whether the same can be said for the dorsal root ganglia (DRG) of the peripheral nervous system (PNS). The mitogen, basic fibroblast growth factor (bFGF) has been previously demonstrated to induce proliferation of CNS neuronal precursors in culture. Since it has also been shown that bFGF is up-regulated within DRG following axotomy, it is quite possible t at the DRG also contains bFGF-responsive neuronal precursors. As a result, 'in vitro' and 'in vivo' experiments were undertaken in order to explore this possibility. The addition of bFGF to cell cultures of early postnatal DRG induced a proliferative response that became evident by the formation of spherical aggregates that stained for the CNS stem cell marker nestin. The replacement of bFGF with trophic factors induced similar cell clusters to differentiate into cells that morphologically resembled DRG neurons, stained for neuronal markers, and generated action potentials. Furthermore, bromodeoxyuridine (BrdU), used as a marker of cytogenesis, was detected in neurofilament-160 + (NF-160+) and/or microtubule associated protein + (MAP-2)+ cells that morphologically resembled neurons. Nerve growth factor (NGF) and sonic hedgehog (Shh) were also capable of producing spherical, process bearing, cell aggregates that stained for neuronal markers. Thus, the DRG appears to contain neuronal precursors that can proliferate in response to several mitogens. Sciatic nerve lesion experiments in juvenile rats were employed to demonstrate that neurogenesis occurs normally following nerve injury. These studies demonstrated a consistent ~40% relative increase in proliferating cells (BrdU +) on the lesioned side compared to the contralateral unlesioned DRG. This observed proliferative response appeared to be greater at 1 week than 2 weeks postaxotomy. Many BrdU+ cells also appeared to stain for the neuronal marker neuron-specific enolase (NSE) suggesting the presence of neuronal precursors. These double-labeled cells were preferentially upregulated in the ipsilateral ganglia, reaching maximal numbers within the first 48 hour after nerve transection. However, this upregulation was transient, lasting for only 1 week. Similar cells (BrdU+/NSE+) were also identified in adult DRG post-axotomy. In addition, BrdU+ labeling in neurons previously anterogradely labeled with Flouro-Gold suggest that pre-existing neurons within adult DRG can become mitotic. These results support the hypothesis that DRG contain neural precursors throughout life that can proliferate and subsequently differentiate into neurons in response to injury. These findings may indicate a greater range of plasticity that is available to somatosensory systems during maturation and following injury, perhaps to replace ineffectual or dying neurons.