title: Targeting epileptogenesis-associated induction of neurogenesis by enzymatic depolysialylation of NCAM counteracts spatial learning dysfunction but fails to impact epilepsy development.
abstract: 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.
authors.affiliation: Institute of Pharmacology, Toxicology, and Pharmacy, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Anton
authors.initials: A
authors.lastname: Pekcec
authors.forename: Christina
authors.initials: C
authors.lastname: Fuest
authors.forename: Martina
authors.initials: M
authors.lastname: Mühlenhoff
authors.forename: Rita
authors.initials: R
authors.lastname: Gerardy-Schahn
authors.forename: Heidrun
authors.initials: H
authors.lastname: Potschka
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D001973:Bromodeoxyuridine / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004558:Electric Stimulation / Q000009:adverse effects; D004569:Electroencephalography; D005106:Exploratory Behavior / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006026:Glycoside Hydrolases / Q000008:administration & dosage; D006624:Hippocampus / Q000473:pathology; D008297:Male; D018782:Maze Learning; D019006:Neural Cell Adhesion Molecules; D009474:Neurons / Q000502:physiology*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012794:Sialic Acids / Q000378:metabolism*; D013226:Status Epilepticus / Q000188:drug therapy / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D013997:Time Factors
chemical_list: D019006:Neural Cell Adhesion Molecules; D012794:Sialic Acids; C021319:polysialic acid; D006026:Glycoside Hydrolases; C090534:endo-alpha-sialidase; D010751:Phosphopyruvate Hydratase; D001973:Bromodeoxyuridine