We experimentally study mechanisms of degeneration and regeneration in the nervous system. To this end, we use several models as well as techniques, to cover different organization levels at diverse tissular locations.
AXONAL DEGENERATION AS A TARGET FOR NEUROPROTECTION
Axonal degeneration is an active mechanism involved in a variety of neurodegenerative conditions triggered by mechanical, metabolic, infectious, toxic, hereditary and inflammatory stimuli. Importantly, axonal degeneration and synapse loss have been proposed as an early event and major contributor to neuronal death in several neurodegenerative conditions, including Parkinson, Alzheimer, Huntington, demyelinating, motoneuron, and prion diseases. Axon degeneration can cause permanent loss of function, so it represents a focus for neuroprotective strategies.
VESICULAR TRANSFER BETWEEN GLIA AND AXONS
Glial cells and neurons have multiple mechanisms for bidirectional comunication. We have shown that transcellular transfer of macromolecules take place from glia to axons after injury (Court et al., 2008) and during axonal regeneration (Court et al., 2011). We are currently studying the communication and macromolecular transfer mechanisms between glial cells and axons mediated by secreted vesicles. Our ultimate goal is to define the role of vesicular transfer between glia and neurons in the regulation of different axonal processes, including local protein synthesis and axonal regeneration in the peripheral and central nervous system.
FUNCTIONAL RECOVERY AFTER SPINAL CORD INJURY
Spinal Cord Injuries (SCI) are devastating conditions leading to partial or complete paralysis with tremendous social and economic impacts. Currently there are no effective therapies for functional recovery after SCI. In our lab, we are approaching the problem in both basic and applied research levels using mice and rats as experimental models. In collaboration with Dr. Claudio Hetz at Univeridad de Chile, we have recently demosntrated an important role of the Unfolded Protein Response (UPR) in locomotor recovery after spinal cord injury (see publications: Valuenzuela et al. Cell Death Disease, 2011).