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Targeting epileptogenesis‐associated induction of neurogenesis by enzymatic depolysialylation of NCAM counteracts spatial learning dysfunction but fails to impact epilepsy development
Author(s) -
Pekcec Anton,
Fuest Christina,
Mühlenhoff Martina,
GerardySchahn Rita,
Potschka Heidrun
Publication year - 2008
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.05172.x
Subject(s) - neurogenesis , epileptogenesis , polysialic acid , neural cell adhesion molecule , neuroscience , epilepsy , neuroplasticity , hippocampal formation , status epilepticus , psychology , neural development , chemistry , cell , cell adhesion , biochemistry , gene
Polysialylation is a post‐translational modification of the neural cell adhesion molecule (NCAM), which in the adult brain promotes structural changes in regions of neurogenesis and neuroplasticity. Because a variety of plastic changes including neurogenesis have been suggested to be functionally involved in the pathophysiology of epilepsies, it is of specific interest to define the impact of the polysialic acid (PSA)‐NCAM system on development of this disease and associated comorbidities. Therefore, we studied the impact of transient enzymatic depolysialylation of NCAM on the pathophysiology in an electrically induced rat post‐status epilepticus (SE) model. Loss of PSA counteracted the SE‐induced increase in neurogenesis in a significant manner. This effect of endoneuraminidase (endoN) treatment on hippocampal neurogenesis did not impact the subsequent development of spontaneous seizures. In contrast, transient lack of PSA during SE and in the early phase of epileptogenesis exhibited a cognition sparing effect as revealed in the Morris water maze paradigm. In conclusion, our data do not support a central role of neurogenesis in the development of a hyperexcitable epileptic network. However, in view of the cognition‐sparing effect, the transient modulation of the PSA‐NCAM system seems to allow beneficial long‐term disease modification, which might be mediated by the partial normalization of neurogenesis.