Journal article
Regulator of G protein signaling 6 mediates exerciseinduced recovery of hippocampal neurogenesis, learning, and memory in a mouse model of Alzheimer's disease
Neural regeneration research, Vol.20(10), pp.2969-2981
10/2025
DOI: 10.4103/NRR.NRR-D-23-01993
PMCID: PMC11826473
PMID: 39248184
Abstract
Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer's disease. Adult hippocampal neurogenesis is reduced in patients with Alzheimer's disease. Exercise stimulates adult hippocampal neurogenesis in rodents and improves memory and slows cognitive decline in patients with Alzheimer's disease. However, the molecular pathways for exercise-induced adult hippocampal neurogenesis and improved cognition in Alzheimer's disease are poorly understood. Recently, regulator of G protein signaling 6 (RGS6) was identified as the mediator of voluntary running–induced adult hippocampal neurogenesis in mice. Here, we generated novel RGS6 fl/fl ; APP SWE mice and used retroviral approaches to examine the impact of RGS6 deletion from dentate gyrus neuronal progenitor cells on voluntary running–induced adult hippocampal neurogenesis and cognition in an amyloid-based Alzheimer's disease mouse model. We found that voluntary running in APP SWE mice restores their hippocampal cognitive impairments to that of control mice. This cognitive rescue was abolished by RGS6 deletion in dentate gyrus neuronal progenitor cells, which also abolished running-mediated increases in adult hippocampal neurogenesis. Adult hippocampal neurogenesis was reduced in sedentary APP SWE mice versus control mice, with basal adult hippocampal neurogenesis reduced by RGS6 deletion in dentate gyrus neural precursor cells. RGS6 is expressed in neurons within the dentate gyrus of patients with Alzheimer's disease with significant loss of these RGS6-expressing neurons. Thus, RGS6 mediates voluntary running -induced rescue of impaired cognition and adult hippocampal neurogenesis in APP SWE mice, identifying RGS6 in dentate gyrus neural precursor cells as a possible therapeutic target in Alzheimer's disease.
Details
- Title: Subtitle
- Regulator of G protein signaling 6 mediates exerciseinduced recovery of hippocampal neurogenesis, learning, and memory in a mouse model of Alzheimer's disease
- Creators
- Mackenzie M. Spicer - University of IowaJianqi Yang - University of IowaDaniel Fu - University of IowaAlison N. DeVore - University of IowaMarisol Lauffer - University of Iowa, Psychological and Brain SciencesNilufer S Atasoy - University of Iowa, Neuroscience and PharmacologyDeniz Atasoy - University of IowaRory A Fisher - University of Iowa, Iowa Neuroscience Institute
- Resource Type
- Journal article
- Publication Details
- Neural regeneration research, Vol.20(10), pp.2969-2981
- DOI
- 10.4103/NRR.NRR-D-23-01993
- PMID
- 39248184
- PMCID
- PMC11826473
- NLM abbreviation
- Neural Regen Res
- ISSN
- 1673-5374
- eISSN
- 1876-7958
- Publisher
- WOLTERS KLUWER MEDKNOW PUBLICATIONS; MUMBAI
- Language
- English
- Electronic publication date
- 09/06/2024
- Date published
- 10/2025
- Academic Unit
- Neurology; Psychiatry; Psychological and Brain Sciences; Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984701765502771
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