Ablation of aberrant neurogenesis fails to attenuate cognitive deficit of chronically epileptic mice.
Epilepsy Res
; 142: 1-8, 2018 05.
Article
em En
| MEDLINE
| ID: mdl-29524833
ABSTRACT
Pilocarpine-induced acute seizures strongly induce aberrant hippocampal neurogenesis, characterized by increased proliferation of neural progenitors and abnormal integrations of newly generated granule cells - hilar ectopic granule cells (EGCs), mossy fibre sprouting (MFS), and hilar basal dendrites (HBDs), which may disturb hippocampal neuronal circuits and thus contribute to cognitive impairment in temporal lobe epilepsy (TLE) patients and animal models. Previous studies via ablating hippocampal neurogenesis after acute seizures produced inconsistent results regarding the development of long-term cognitive impairment. Furthermore, a sufficient decrease of subsequent abnormal integrations in chronically epileptic hippocampus was not well-established in these studies. Therefore, the link between seizure-induced aberrant hippocampal neurogenesis and cognitive decline associated with epilepsy is still in need to be clarified. In this study, the mice were injected with methylazoxymethanol acetate (MAM) both before and after pilocarpine-induced status epilepticus (SE) to achieve an overall ablation of newborn cells contributing to the pathological recruitment. In addition, a protracted time point was chosen for behavioral testing considering it takes a fairly long time for newborn granule cells to adequately develop abnormal integrations, especially MFS. Although an overall reduction of abnormal integrations, including EGCs, MFS and HBDs was confirmed following the ablation regime, the performance of ablated and non-ablated mice in the Morris Water Maze (MWM) task did not differ. The current findings therefore provide novel evidences that ablation of neurogenesis with an overall decrease of abnormal integrations cannot attenuate subsequent cognitive impairment at least in the model used in this study.
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Base de dados:
MEDLINE
Assunto principal:
Estado Epiléptico
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Acetato de Metilazoximetanol
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Transtornos Cognitivos
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Hipocampo
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article