Survival and death of mature avian motoneurons in organotypic slice culture: Trophic requirements for survival and different types of degeneration
- 13 February 2007
- journal article
- research article
- Published by Wiley in Journal of Comparative Neurology
- Vol. 501 (5) , 669-690
- https://doi.org/10.1002/cne.21157
Abstract
We have developed an organotypic culture technique that uses slices of chick embryo spinal cord, in which trophic requirements for long‐term survival of mature motoneurons (MNs) were studied. Slices were obtained from E16 chick embryos and maintained for up to 28 days in vitro (DIV) in a basal medium. Under these conditions, most MNs died. To promote MN survival, 14 different trophic factors were assayed. Among these 14, glial cell line‐derived neurotrophic factor (GDNF) and vascular endothelial growth factor were the most effective. GDNF was able to promote MN survival for at least 28 DIV. K+ depolarization or caspase inhibition prevented MN death but also induced degenerative‐like changes in rescued MNs. Agents that elevate cAMP levels promoted the survival of a proportion of MNs for at least 7 DIV. Examination of dying MNs revealed that, in addition to cells exhibiting a caspase‐3‐dependent apoptotic pattern, some MNs died by a caspase‐3‐independent mechanism and displayed autophagic vacuoles, an extremely convoluted nucleus, and a close association with microglia. This organotypic spinal cord slice culture may provide a convenient model for testing conditions that promote survival of mature‐like MNs that are affected in late‐onset MN disease such as amyotrophic lateral sclerosis. J. Comp. Neurol. 501:669–690, 2007.Keywords
This publication has 122 references indexed in Scilit:
- GDNF-deprived sympathetic neurons die via a novel nonmitochondrial pathwayThe Journal of cell biology, 2003
- Rescue of developing spinal motoneurons from programmed cell death by the GABAA agonist muscimol acts by blockade of neuromuscular activity and increased intramuscular nerve branchingMolecular and Cellular Neuroscience, 2003
- Neuroprotective Utility and Neurotrophic Action of Neurturin in Postnatal Motor Neurons: Comparison with GDNF and PersephinMolecular and Cellular Neuroscience, 1999
- Neurotrophic Survival Molecules for Motoneurons: An Embarrassment of RichesNeuron, 1996
- Programmed cell death during the earliest stages of spinal cord development in the chick embryo: A possible means of early phenotypic selectionJournal of Comparative Neurology, 1994
- Neurotrophic agents prevent motoneuron death following sciatic nerve section in the neonatal mouseJournal of Neurobiology, 1994
- Intracellular calcium regulates the survival of early sensory neurons before they become dependent on neurotrophic factorsNeuron, 1992
- Lack of evidence for cell death among avian spinal cord interneurons during normal development and following removal of targets and afferentsJournal of Neurobiology, 1991
- Expression of nerve growth factor receptor mRNA is developmentally regulated and increased after axotomy in rat spinal cord motoneuronsNeuron, 1989
- Motoneurone survival requirements during development: the change from immature astrocyte dependence to myotube dependenceDevelopmental Brain Research, 1986