Neural proliferation in the sensory ganglia following capsaicin-induced neuronal death
Gallaher, Zachary R.
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In the adult mammalian nervous system, new neurons are created by the process of neurogenesis in only two accepted regions, the subventricular and subgranular zones. However, we have reported that the number of neurons in the nodose ganglia (NG) is restored following the death of half of the neuronal population by capsaicin, a neurotoxin selective for C-type neurons expressing the capsaicin receptor, TRPV-1. It is not known whether similar neuronal recovery occurs in other sensory ganglia. Additionally, the progression of neural proliferation remains to be characterized. To determine if this type of neuronal recovery occurs in other sensory ganglia, we examined the dorsal root ganglia (DRG) following capsaicin exposure. Our results showed that approximately two-thirds of the spinal projections to the peritoneal cavity from the DRG were degenerated 30 days following capsaicin. However, 60 days after capsaicin, there was a restoration in the number of spinal projections. A similar pattern of loss and restoration was observed with respect to key signaling proteins NR1 and Nav1.8. To determine the cellular source of new neurons in sensory ganglia, we examined the NG and DRG for the stem cell marker, nestin. We found nestin was expressed in a population of supporting satellite glial cells (SGCs). To define the progression of neurogenesis, we examined the DRG and NG for the incorporation of the proliferation markers. Marker incorporation showed that nestin-expressing SGCs increased division immediately following capsaicin. At later time points, mature neurons with these markers were found. Neuronal differentiation was supported by the presence of immature neuronal morphologies in culture following capsaicin. To determine if newly formed neurons are functional, we tested for the return of sensations mediated by C-type neurons in the NG (satiety) and DRG (heat). Following the restoration of neuronal numbers and axonal projections, responses to the satiety signal, cholecystokinin-8, and noxious heat of 55 °C were restored. Together, our results indicate that adult sensory ganglia have the capacity to generate new neurons when SGC neural progenitors are activated by injury. With further investigation, this may lead to the development of therapeutic interventions for treating damage to the nervous system.