Arginase-1 deficiency in neural cells does not contribute to neurodevelopment or functional outcomes after sciatic nerve injury
| Autor: | Colin D. Funk, A. Elizabeth de Guzman, Laurel L. Ballantyne, Brian J. Nieman, Christopher R. Richmond, Nader Ghasemlou |
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| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Nervous system medicine.medical_specialty Urea cycle disorder Biology Mice 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Internal medicine medicine Animals Mice Knockout Neurons Arginase Brain Recovery of Function Cell Biology Sciatic nerve injury Nerve injury medicine.disease Mice Inbred C57BL 030104 developmental biology Endocrinology medicine.anatomical_structure Urea cycle Peripheral nervous system Neuroglia Sciatic Neuropathy medicine.symptom 030217 neurology & neurosurgery |
| Zdroj: | Neurochemistry International. 145:104984 |
| ISSN: | 0197-0186 |
| Popis: | Arginase-1 (Arg1) is an enzyme controlling the final step of the urea cycle, with highest expression in the liver and lower expression in the lungs, pancreas, kidney, and some blood cells. Arg1 deficiency is an inherited urea cycle disorder presenting with neurological dysfunction including spastic diplegia, intellectual and growth retardation, and encephalopathy. The contribution of Arg1 expression in the central and peripheral nervous system to the development of neurological phenotypes remains largely unknown. Previous studies have shown prominent arginase-1 expression in the nervous system and post-peripheral nerve injury in mice, but very low levels in the naïve state. To investigate neurobiological roles of Arg1, we created a conditional neural (n)Arg1 knockout (KO) mouse strain, with expression eliminated in neuronal and glial precursors, and compared them to littermate controls. Long-term analysis did not reveal any major differences in blood amino acid levels, body weight, or stride gait cycle from 8 to 26-weeks of age. Brain structure measured by magnetic resonance imaging at 16-weeks of age observed only a significant decrease in the volume of the mammillary bodies. We also assessed whether nArg1, which is expressed by sensory neurons after injury, may play a role in regeneration following sciatic nerve crush. Only subtle differences were observed in locomotor and sensory recovery between nArg1 KO and control mice. These results suggest that arginase-1 expression in central and peripheral neural cells does not contribute substantially to the phenotypes of this urea cycle disorder, nor is it likely crucial for post-injury regeneration in this mouse model. |
| Databáze: | OpenAIRE |
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