Diapause induces functional axonal regeneration after necrotic insult in C. elegans

Abstract

Many neurons are unable to regenerate after damage. The ability to regenerate after an insult depends on life stage, neuronal subtype, intrinsic and extrinsic factors. C. elegans is a powerful model to test the genetic and environmental factors that affect axonal regeneration after damage, since its axons can regenerate after neuronal insult. Here we demonstrate that diapause promotes the complete morphological regeneration of truncated touch receptor neuron (TRN) axons expressing a neurotoxic MEC-4(d) DEG/ENaC channel. Truncated axons of different lengths were repaired during diapause and we observed potent axonal regrowth from somas alone. Complete morphological regeneration depends on DLK-1 but neuronal sprouting and outgrowth is DLK-1 independent. We show that TRN regeneration is fully functional since animals regain their ability to respond to mechanical stimulation. Thus, diapause induced regeneration provides a simple model of complete axonal regeneration which will greatly facilitate the study of environmental and genetic factors affecting the rate at which neurons die.

Bacterially produced GABA protects neurons from degeneration

“…Hence, we determined the response to gentle touch in worms fed the different strains to test whether morphological protection shown in Figure 1B translate into functional responses. Figure 1E shows that the number of responses in worms correlates with the morphological categories AxW and AxL, the two axonal categories defined as functional in previous work [22].…”

“…This demonstrated that DAF-16 is required for the neuroprotection effect of the HT115 diet. Noteworthy, the daf-16 mutation completely abolished the protection of TRNs previously observed at 25°C in mec-4d background [22] in both bacteria, suggesting that the daf-16 mutation significantly lowers the threshold for neurodegenerative stimuli. The effect of increased degeneration in daf-16; mec-4d though much more dramatic in E. coli HT115 is also observed in OP50.…”

“…It has been already reported that at hatching, four embryonic TRN, two Anterior Lateral Microtubule (ALMs) and two Posterior Lateral Microtubule (PLM) neurons have already degenerated when growing at 20°C in this model [16,24]. At 25°C however, degeneration proceeds at a slower rate [16,22]. To analyze the degeneration rate of ALM and PLM neurons, L4 animals were grown at 25°C and their progenies synchronized at birth.…”

“…In our experiments DAF-2 inactivation did not increase HT115 protection, suggesting they act in the same pathway. Neuroprotective and neuroregenerative effects of DAF-2 downregulation involve the function of DAF-16 [16,22,45]. Comparison of DAF-16 nuclear translocation between diets showed that at 24 hours DAF-16 was increased in the nuclei of animals feeding on HT115 compared to OP50.…”

“…The degeneration of the TRN begins with the fragmentation of the axon followed by the swelling of the soma. Noteworthy, the use of this model has allowed determining interventions than can delay neurodegeneration, such as caloric restriction, antioxidant treatment and mitochondria blockage [16], as well as diapause entry [22]. In this study, we evaluated the rate of degeneration of C. elegans neurons in different dietary bacteria and found that specific dietary bacteria promote protection from neuronal degeneration.…”