Dorsal Root Ganglia Sensory Neuronal Cultures: a tool for drug discovery for peripheral neuropathies

Abstract

BACKGROUND: Peripheral neuropathies affect many people worldwide and are caused by or associated with a wide range of conditions, both genetic and acquired. Current therapies are directed at symptomatic control because no effective regenerative treatment exists. Primary challenge is that mechanisms that lead to distal axonal degeneration, a common feature of all peripheral neuropathies, are largely unknown. OBJECTIVE/METHODS: To address the role and specific characteristics of dorsal root ganglia (DRG) derived sensory neuron culture system as a useful model in evaluating the pathogenic mechanisms of peripheral neuropathies and examination and validation of potential therapeutic compounds. A thorough review of the recent literature was completed and select examples of the use of DRG neurons in different peripheral neuropathy models were chosen to highlight the utility of these cultures. CONCLUSION: Many useful models of different peripheral neuropathies have been developed using DRG neuronal culture and potential therapeutic targets have been examined, but so far none of the potential therapeutic compounds have succeeded in clinical trials. In recent years, focus has changed to evaluation of axon degeneration as the primary outcome measure advocating a drug development strategy starting with phenotypic drug screening, followed by validation in primary complex co-cultures and animal models.

Figure 1

Schematic view of preparation of dissociated and explant DRG sensory neuronal cultures.

Figure 2

Compartmented sensory neuronal cultures. A: schematic and ß-III tubulin immuno-stained cultures; B: phase contrast images of middle and side chambers (arrow head: growth cone); C-D: TuJ1 immuno-staining of neurons and distal axons; E: Schwann cells (red colored) ensheating axons in side chambers.