RT Journal Article
T1 Abolition of aberrant neurogenesis ameliorates cognitive impairment after stroke in mice
A1 Cuartero Desviat, María Isabel
A1 Parra Gonzalo, Juan De La
A1 Pérez Ruiz, Alberto
A1 Bravo-Ferrer, Isabel
A1 Durán Laforet, Violeta
A1 García Culebras, Alicia
A1 García Segura, Juan Manuel
A1 Dhaliwal, Jagroop
A1 Frankland, Paul
A1 Lizasoaín Hernández, Ignacio
A1 Moro Sánchez, María Ángeles
AB Poststroke cognitive impairment is considered one of the main complications during the chronic phase of ischemic stroke. In the adult brain, the hippocampus regulates both encoding and retrieval of new information through adult neurogenesis. Nevertheless, the lack of predictive models and studies based on the forgetting processes hinders the understanding of memory alterations after stroke. Our aim was to explore whether poststroke neurogenesis participates in the development of long-term memory impairment. Here, we show a hippocampal neurogenesis burst that persisted 1 month after stroke and that correlated with an impaired contextual and spatial memory performance. Furthermore, we demonstrate that the enhancement of hippocampal neurogenesis after stroke by physical activity or memantine treatment weakened existing memories. More importantly, stroke-induced newborn neurons promoted an aberrant hippocampal circuitry remodeling with differential features at ipsi- and contralesional levels. Strikingly, inhibition of stroke-induced hippocampal neurogenesis by temozolomide treatment or using a genetic approach (Nestin-CreERT2/NSE-DTA mice) impeded the forgetting of old memories. These results suggest that hippocampal neurogenesis modulation could be considered as a potential approach for treatment of poststroke cognitive impairment.
PB American Society for Clinical Investigation
SN 0021-9738
YR 2019
FD 2019
LK https://hdl.handle.net/20.500.14352/94485
UL https://hdl.handle.net/20.500.14352/94485
LA eng
NO Cuartero, María Isabel, et al. «Abolition of Aberrant Neurogenesis Ameliorates Cognitive Impairment after Stroke in Mice». Journal of Clinical Investigation, vol. 129, n.o 4, febrero de 2019, pp. 1536-50. https://doi.org/10.1172/JCI120412.
NO This work was supported by grants from the Spanish Ministry of Economy and Competitiveness (MINECO) (SAF2015-68632-R to MAM), the Instituto de Salud Carlos III (ISCIII) (FIS PI17/01601 to IL), and ISCIII cofinanced by the Fondo Europeo de Desarrollo Regional (FEDER) “Una manera de hacer Europa” RETICS (RD12/0014/0003 to IL), and the Canadian Institutes of Health Research (FDN143227to PWF).
NO Canadian Institutes of Health Research
NO Ministerio de Economía y Competitividad (España)
NO European Commission
NO Instituto de Salud Carlos III
DS Docta Complutense
RD 13 abr 2025