Woitke, Florus
[Author]
;
Witte, Otto W.
[Degree supervisor];
Türk, Elisabeth
[Degree supervisor];
Redecker, Christoph
[Degree supervisor]Friedrich-Schiller-Universität Jena
Einfluss von körperlicher Aktivität auf die Integration neuer Nervenzellen im Gyrus dentatus nach experimentellen Schlaganfällen
University thesis:
Dissertation, Friedrich-Schiller-Universität Jena, 2021
Footnote:
Kumulative Dissertation, enthält Zeitschriftenaufsätze
Tag der Verteidigung: 01.06.2021
Zeitschriftenaufsatz in englischer Sprache
Description:
Stroke significantly stimulates neurogenesis in the adult dentate gyrus, though the functional role of this postlesional response is mostly unclear. Recent findings suggest that new-born neurons generated in the context of stroke may fail to correctly integrate into pre-existing networks. We hypothesized that increased neurogenesis in the dentate gyrus following stroke is associated with aberrant neurogenesis and impairment of hippocampus-dependent memory. To address these questions, we used the middle cerebral artery occlusion model (MCAO) in mice. Animals were housed either under standard conditions or with free access to running wheels. New-born granule cells were labelled with the thymidine analogue EdU and retroviral vectors. To assess memory performance, we employed a modified version of the Morris water maze (MWM) allowing differentiation between hippocampus dependent and independent learning strategies. New-born neurons were morphologically analysed using confocal microscopy and Neurolucida system at 7 weeks. We found that neurogenesis was significantly increased following MCAO. Animals with MCAO needed more time to localize the platform and employed less hippocampus-dependent search strategies in MWM versus controls. Confocal studies revealed an aberrant cell morphology with basal dendrites and an ectopic location (e.g. hilus) of new granule cells born in the ischemic brain. Running increased the number of new neurons but also enhanced aberrant neurogenesis. Running, did not improve the general performance in the MWM but slightly promoted the application of precise spatial search strategies. In conclusion, ischemic insults cause hippocampal-dependent memory deficits which are associated with aberrant neurogenesis in the dentate gyrus indicating ischemia-induced maladaptive plasticity in the hippocampus.