Collateral Sprouting of Peripheral Sensory Neurons Exhibits a Unique Transcriptomic Profile.

Peripheral nerve injuries result in motor and sensory dysfunction which can be recovered by compensatory or regenerative processes. In situations where axonal regeneration of injured neurons is hampered, compensation by collateral sprouting from uninjured neurons contributes to target reinnervation and functional recovery. Interestingly, this process of collateral sprouting from uninjured neurons has been associated with the activation of growth-associated programs triggered by Wallerian degeneration. Nevertheless, the molecular alterations at the transcriptomic level associated with these compensatory growth mechanisms remain to be fully elucidated. We generated a surgical model of partial sciatic nerve injury in mice to mechanistically study degeneration-induced collateral sprouting from spared fibers in the peripheral nervous system. Using next-generation sequencing and Ingenuity Pathway Analysis, we described the sprouting-associated transcriptome of uninjured sensory neurons and compare it with the activated by regenerating neurons. In vitro approaches were used to functionally assess sprouting gene candidates in the mechanisms of axonal growth. Using a novel animal model, we provide the first description of the sprouting transcriptome observed in uninjured sensory neurons after nerve injury. This collateral sprouting-associated transcriptome differs from that seen in regenerating neurons, suggesting a molecular program distinct from axonal growth. We further demonstrate that genetic upregulation of novel sprouting-associated genes activates a specific growth program in vitro, leading to increased neuronal branching. These results contribute to our understanding of the molecular mechanisms associated with collateral sprouting in vivo. The data provided here will therefore be instrumental in developing therapeutic strategies aimed at promoting functional recovery after injury to the nervous system.

A REDCap application that links researchers, animal facility staff and members of the IACUC in animal health monitoring.

Research studies involving animal experimentation are regulated by the Institutional Animal Care and Use Committee (IACUC). To this end, the IACUC must integrate the information provided by the investigators of each preclinical study and the veterinarians from the animal facility in order to monitor and approve the process. Using a paper-based system to collect animal health and welfare data is a common, albeit time-consuming practice, prone to transcription and reading errors, not to mention inconvenient for veterinarians and investigators wishing to make timely and collaborative decisions when animal welfare is at risk. We created a web-based monitoring system focused on animal health with the potential to improve animal welfare. The data management system is based on REDCap software, which enables data integration in order to offer a solution for animal welfare assessment. The proposed scheme includes key indicators of general health status, such as environment, physical/nutritional information, and behavioral parameters during animal breeding and experimentation, as important components of animal welfare. In addition, the system facilitates communication of this information among researchers, animal facility staff, and the IACUC. REDCap is available to non-profit organizations, and may be adapted and replicated by institutions interested in and responsible for animal care, and used in research. REDCap is an excellent tool for promoting good practices that benefit experimental animal health.