The Role of Mossy Cell Death and Activation of Protein Synthesis in the Sprouting of Dentate Mossy Fibers: Evidence from Calretinin and Neo-Timm Staining in Pilocarpine-Epileptic Mice

Summary: Mossy fiber sprouting is a major anatomical reorganization seen in patients with temporal lobe epilepsy and animal models of epilepsy. The final outcome of this reorganization is viewed by many as epileptogenic. Yet, important and relevant data from both human and animal models of epilepsy challenge this prevailing view. Regardless of the outcome of this debate, understanding of the mechanisms that underlie mossy fiber sprouting (MFS) might contribute to our understanding of both the adaptive and maladaptive changes that take place in the nervous system after injury. Available evidence suggests that two events might be crucial for mossy fibers to sprout in epilepsy: the death of mossy cells and the synthesis of trophic factors. The availability of means that prevent MFS, which is normally triggered after induction of status epilepticus, allow for the testing of hypotheses regarding the need for and the sufficiency of specific events for mossy fibers to sprout. We present data on a specific marker for mossy cells, calretinin, in the pilocarpine model of epilepsy in mice. Our data suggest that in the presence of a protein synthesis inhibitor status epilepticus—induced death of mossy cells is not sufficient to trigger mossy fiber sprouting. We suggest that both events, mossy cell death and synthesis of trophic factors, might be necessary for robust MFS to ensue.