Aplicación de un modelo de lesión parcial de nervio ciático para el estudio del transcriptoma asociado a la extensión de axones colaterales

Axonal regeneration is the major mechanism to achieve functional recovery after a nervous system injury, but is not efficient in the central nervous system or after severe damage in the peripheral nervous system. Collateral sprouting represents an alternative repair mechanism in which intact neurons in proximity to injured axons extend axonal collaterals generating new compensating circuits. Currently, it is unknown if sprouting neurons requires the activation of a specific transcriptional program and how different this is from the activated in regenerating neurons.

We established a model of partial sciatic nerve injury to study the collateral sprouting-associated transcriptome in sensory neurons. We showed that collateral sprouting was triggered 7 days after injury with a significant increase at day 14. Myelination was delayed in collaterals compared to axonal regeneration. In vitro studies demonstrated that after being in contact with degenerating axons, intact neurons increase their growth capacity in terms of neurite length and branching. Transcriptomic analysis revealed that collateral sprouting neurons activate a specific transcriptome, including common genes with axonal regeneration and an exclusive transcriptional component. Differential regulation of metabolic pathways was observed, including Rho family GTPases and ILK signaling, which could be crucial for the mechanism of collateral sprouting.

We demonstrate that the model of partial sciatic nerve injury is appropriate for the study of collateral sprouting mechanisms, which include the activation of a unique transcriptome with differential regulation of certain metabolic pathways, providing a solid base for the study of the cellular and molecular mechanisms involved in this type of axonal growth and offer potential therapeutic strategies for functional recovery after a damage to the nervous system.

• Nombre: Dominique Lemaitre Mujica
• Laboratorio: Neurobiología
• Mención: Ciencias Fisiológicas
• Director Tesis: Felipe Court