In vivo study of motoneuron death induced by nerve injury in mice deficient in the caspase 1/ interleukin-1β-converting enzyme

• Published in: Neuroscience 2000, Vol.98 (3), p.573-583
• Main Authors: de Bilbao, F., Giannakopoulos, P., Srinivasan, A., Dubois-Dauphin, M.
• Format: Article
• Language: English
• Subjects: Age Factors; Animals; Animals, Newborn; apoptosis; Apoptosis - physiology; Axotomy; Biological and medical sciences; Caspase 1 - genetics; Caspase 1 - metabolism; Caspase 3; caspases; Caspases - analysis; Caspases - metabolism; Development. Senescence. Regeneration. Transplantation; DNA Fragmentation; facial motoneuron; Facial Nerve - cytology; Facial Nerve - growth & development; Facial Nerve - physiology; Facial Nerve Injuries - genetics; Facial Nerve Injuries - metabolism; Fluorescent Antibody Technique; Fundamental and applied biological sciences. Psychology; ICE knock-out mice; In Situ Nick-End Labeling; Mice; Mice, Knockout; Motor Neurons - cytology; Motor Neurons - enzymology; Nerve Regeneration - physiology; Vertebrates: nervous system and sense organs
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/S0306-4522(00)00100-7

The apoptotic cell death program is orchestrated by members of the caspase family. Among these caspases, several in vitro and in vivo reports indicate that the interleukin-1β-converting enzyme (or caspase 1) may be involved in neurodegenerative processes. In view of these findings, and in order to characterize the role of the interleukin-1β-converting enzyme in mediating or modulating cell death processes in vivo, we have investigated the effects of its deletion on motoneuron survival after a facial nerve transection in newborn and adult interleukin-1β-converting enzyme knock-out mice. During the postnatal period of development, when facial motoneurons are highly vulnerable to axotomy, we did not observe any significant effect of the interleukin-1β-converting enzyme-deletion on the percentage of cell death in the lesioned nuclei. In addition, the spontaneous cell death characteristic of the postnatal period was not altered in knock-out mice. In contrast, in adult knock-out mice, a significant reduction (16%) in the number of surviving facial motoneurons was observed six weeks after axotomy. We therefore conclude that the interleukin-1β-converting enzyme does not appear to be critical for cell death during the postnatal period but may favor motoneuron survival during adulthood. Given the key role of caspase 3 in neuronal apoptosis during embryonic development of the central nervous system, we also investigated the role of this caspase in cell death following axotomy. Combined immunofluorescence revealed that, at least during the postnatal period, axotomized motoneurons that have apoptotic nuclear morphologies were immunopositive for the active form of caspase 3. Double-stained cells could be also observed on the unlesioned side. These results strongly suggest that caspase 3 may be involved in both the postnatal spontaneous- and axotomy-induced facial motoneuron death processes. Similar results were obtained in interleukin-1β-converting enzyme-deficient and wild-type mice, indicating that the interleukin-1β-converting enzyme may not be required for caspase 3 activation.