title: Epileptogenesis following Kainic Acid-Induced Status Epilepticus in Cyclin D2 Knock-Out Mice with Diminished Adult Neurogenesis.
abstract: The goal of this study was to determine whether a substantial decrease in adult neurogenesis influences epileptogenesis evoked by the intra-amygdala injection of kainic acid (KA). Cyclin D2 knockout (cD2 KO) mice, which lack adult neurogenesis almost entirely, were used as a model. First, we examined whether status epilepticus (SE) evoked by an intra-amygdala injection of KA induces cell proliferation in cD2 KO mice. On the day after SE, we injected BrdU into mice for 5 days and evaluated the number of DCX- and DCX/BrdU-immunopositive cells 3 days later. In cD2 KO control animals, only a small number of DCX+ cells was observed. The number of DCX+ and DCX/BrdU+ cells/mm of subgranular layer in cD2 KO mice increased significantly following SE (p<0.05). However, the number of newly born cells was very low and was significantly lower than in KA-treated wild type (wt) mice. To evaluate the impact of diminished neurogenesis on epileptogenesis and early epilepsy, we performed video-EEG monitoring of wt and cD2 KO mice for 16 days following SE. The number of animals with seizures did not differ between wt (11 out of 15) and cD2 KO (9 out of 12) mice. The median latency to the first spontaneous seizure was 4 days (range 2-10 days) in wt mice and 8 days (range 2-16 days) in cD2 KO mice and did not differ significantly between groups. Similarly, no differences were observed in median seizure frequency (wt: 1.23, range 0.1-3.4; cD2 KO: 0.57, range 0.1-2.0 seizures/day) or median seizure duration (wt: 51 s, range 23-103; cD2 KO: 51 s, range 23-103). Our results indicate that SE-induced epileptogenesis is not disrupted in mice with markedly reduced adult neurogenesis. However, we cannot exclude the contribution of reduced neurogenesis to the chronic epileptic state.
authors.affiliation: Laboratory of Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Ilona
authors.initials: I
authors.lastname: Kondratiuk
authors.affiliation: Laboratory of Epileptogenesis, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Plucinska
authors.affiliation: Laboratory of Epileptogenesis, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Diana
authors.initials: D
authors.lastname: Miszczuk
authors.affiliation: Laboratory of Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Grazyna
authors.initials: G
authors.lastname: Wozniak
authors.affiliation: Laboratory of Epileptogenesis, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Kinga
authors.initials: K
authors.lastname: Szydlowska
authors.affiliation: Laboratory of Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Leszek
authors.initials: L
authors.lastname: Kaczmarek
authors.affiliation: Laboratory of Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland; Laboratory of Biological Psychology, University of Finance and Management in Warsaw, Warsaw, Poland; Behavior and Metabolism Research Laboratory, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Filipkowski
authors.affiliation: Laboratory of Epileptogenesis, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Lukasiuk
mesh_terms: D000679:Amygdala / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D056742:Cyclin D2 / Q000172:deficiency*; D000089662:Doublecortin Protein; D004569:Electroencephalography; D007608:Kainic Acid / Q000009:adverse effects* / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D055495:Neurogenesis / Q000187:drug effects / Q000235:genetics; D012640:Seizures / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013226:Status Epilepticus / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology
chemical_list: C486196:Ccnd2 protein, mouse; D056742:Cyclin D2; C000714847:Dcx protein, mouse; D000089662:Doublecortin Protein; D007608:Kainic Acid