Present address: Department of Biology, University of Prince Edward Island, Charlottetown, Prince Edward Island, Canada.
Aldolase C-positive cerebellar Purkinje cells are resistant to delayed death after cerebral trauma and AMPA-mediated excitotoxicity
Article first published online: 1 AUG 2007
European Journal of Neuroscience
Volume 26, Issue 3, pages 649–656, August 2007
How to Cite
Slemmer, J. E., Haasdijk, E. D., Engel, D. C., Plesnila, N. and Weber, J. T. (2007), Aldolase C-positive cerebellar Purkinje cells are resistant to delayed death after cerebral trauma and AMPA-mediated excitotoxicity. European Journal of Neuroscience, 26: 649–656. doi: 10.1111/j.1460-9568.2007.05708.x
- Issue published online: 1 AUG 2007
- Article first published online: 1 AUG 2007
- Received 11 June 2006, revised 9 May 2007, accepted 18 June 2007
- controlled cortical impact;
- traumatic brain injury;
- zebrin II
The cerebellum has been shown to be vulnerable to global ischemic damage in tightly controlled zones of Purkinje cells (PCs) that lack aldolase C, an enzyme critical for glycolysis. Here, we investigated whether aldolase C-negative PCs were more likely to die after cerebral trauma in vivo, and whether this death was mediated by excitotoxic [α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-mediated] means in vitro. Mice were subjected to controlled cortical impact, or remained uninjured, and were killed at 6 h, 24 h or 7 days after injury. Cerebellar sections (both ipsilateral and contralateral to the site of cerebral injury) were stained against aldolase C and calbindin (a marker of PCs). The number of viable, calbindin-positive PCs decreased significantly at 24 h and 7 days after injury, and the percentage of surviving, aldolase C-positive PCs significantly increased at those time-points. In addition, we subjected murine cerebellar cultures to AMPA (30 µm, 20 min), which killed a significant number of PCs at 24 h post-treatment. A similar number of PCs was lost after transfection with aldolase C siRNA, and this effect was exacerbated in transfected cultures treated with AMPA. The results from the present study indicate that aldolase C provides marked neuroprotection to PCs after trauma and excitotoxicity.