Physical activity compensates for isoflurane-induced selective impairment of neuronal progenitor cell proliferation in the young adult hippocampus

Saskia Böckmann; Deetje Iggena; Stefanie Schreyer; André Rex; Barbara Steiner

doi:10.1016/j.bbr.2023.114675

Physical activity compensates for isoflurane-induced selective impairment of neuronal progenitor cell proliferation in the young adult hippocampus

Behav Brain Res. 2023 Oct 18:455:114675. doi: 10.1016/j.bbr.2023.114675. Epub 2023 Sep 19.

Authors

Saskia Böckmann¹, Deetje Iggena², Stefanie Schreyer¹, André Rex³, Barbara Steiner¹

Affiliations

¹ Department of Neurology, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany.
² Department of Neurology, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany. Electronic address: deetje.iggena@charite.de.
³ Department of Neurology, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; Center for Stroke Research Berlin, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany.

PMID: 37734489
DOI: 10.1016/j.bbr.2023.114675

Abstract

General anesthesia is considered a risk factor for postoperative cognitive dysfunction. However, it is unclear what the neuronal and cognitive consequences of general anesthesia are and whether they can be treated. One possible pathomechanism is hippocampal neurogenesis. We investigated how the anesthetic isoflurane affects adult hippocampal neurogenesis and associated cognitive functions and whether the neurogenic stimulus of physical activity reverses isoflurane-induced changes. We exposed young adult mice to isoflurane (ISO) - half had access to a running wheel (ISO-RW). Both groups were compared with a control condition (CTR; CTR-RW). Cell proliferation and survival in the dentate gyrus of the hippocampus were quantified histologically 48 h and 3 weeks after anesthesia by bromodeoxyuridine incorporation. Cell phenotype was determined by expression of neuronal markers, and the extent of continuous endogenous neuronal proliferation was estimated from the number of doublecortin-positive cells. The Morris water maze was used to test hippocampus-dependent functions. We found that isoflurane decreased proliferation of neuronal progenitor cells, whereas survival of mature neurons remained intact. Consistent with intact neuronal survival, spatial memory associated with neurogenesis also proved intact in the Morris water maze despite isoflurane exposure. Physical activity attenuated the observed neuronal changes by preventing the decrease in newborn neuronal progenitor cells and the decline in continuous endogenous neuronal proliferation in isoflurane-treated animals. In conclusion, isoflurane selectively impairs neuronal proliferation but not survival or neurogenesis-linked cognition in adult mice. The observed adverse effects can be attenuated by physical activity, a cost-effective means of preventing the neurogenic consequences of general anesthesia.

Keywords: Hippocampal neurogenesis; Isoflurane; Physical activity; Postoperative cognitive dysfunction; Spatial memory.