The rise in cytoplasmic ubiquitin levels is an early step in the response of parasympathetic ganglionic neurons to axonal injury followed by regeneration.
We investigated the involvement of ubiquitin in the neuronal response to axonal injury in the quail parasympathetic ciliary ganglion by immuno-light and electron microscopy. Image analysis of immunoreacted cryosections shows that ubiquitin-immunoreactivity in the ciliary neurons increases significantly 6 hours after postganglionic nerve crush. The immunolabeling reaches a peak 1 day after injury and begins to decrease between days 3 and 6 when, in contrast to the cytoplasm, numerous highly eccentric nuclei are strongly immunolabeled. Electron microscopy shows ubiquitin-immunoreactivity associated with cytoplasmic organelles and with several postsynaptic densities of the numerous synapses established by the preganglionic boutons on the soma of the ciliary neurons. The number of immunopositive postsynaptic densities increases significantly 1 day after axonal damage, followed by temporary detachment of the preganglionic boutons from the injured neurons between days 3 and 6. The early increase in cytoplasmic ubiquitin-immunoreactivity suggests a prompt ubiquitination of damaged proteins addressed to degradation, while the nuclear immunolabeling may reflect high histone ubiquitination, a process involved in keeping chromatin transcriptionally active. The possible ubiquitin-mediated removal of postsynaptic apparatus constituents such as ACh receptors, proteins involved in their clustering and stabilization, and/or adhesion molecules may be a crucial step for the detachment of the preganglionic boutons, thus favoring injury-induced synaptic plasticity.
De Stefano
M E
ME
Dipartimento di Biologia Cellulare dello Sviluppo, Università La Sapienza, Rome, Italy.
Squitti
R
R
Toschi
G
G
D000818:Animals; D001369:Axons / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism; D003370:Coturnix; D003593:Cytoplasm / Q000378:metabolism*; D005726:Ganglia, Parasympathetic / Q000293:injuries* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008854:Microscopy, Electron; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D014452:Ubiquitins / Q000378:metabolism*
D014452:Ubiquitins