Presentation Type
Poster
Location
Portland State University
Start Date
5-7-2019 11:00 AM
End Date
5-7-2019 1:00 PM
Subjects
Transcription factors, Active oxygen -- Pathophysiology, Active oxygen -- Physiological effect, Oxidative stress, Neuroplasticity
Abstract
Background: As the brain ages, free radicals accumulate and cause damage to cellular macromolecules. This increased oxidative damage is thought to contribute to the cognitive decline observed in aging. Activation of the antioxidant regulatory transcription factor NRF2 (Nuclear factor erythroid-derived 2) has been shown to improve neuronal health in aging and neurodegenerative diseases. Yet exactly how NRF2 participates in maintaining synaptic and cognitive function has not been fully elucidated. This study investigates how loss of NRF2 affects synaptic density and cognitive performance in aged mice.
Methods: Dendritic arborization and synaptic was evaluated in hippocampal neurons isolated from mice lacking NRF2 (NRF2KO) and from wild-type (WT) C57BL6 mice. Mitochondrial function of these neurons was evaluated using the Seahorse XF platform. Hippocampal and cortical expression of synaptic genes were measured.
Results: NRF2KO neurons had significantly reduced dendritic complexity relative to WT neurons as well as reduced synaptic gene expression. Similar deficits in synaptic gene expression were observed in the brains of aged NRF2KO mice relative to WT mice.
Conclusions: These data point to a role for NRF2 in maintaining synaptic health and cognitive function during aging and suggest that the transcription factor may be a viable target for cognitive enhancing interventions. Because increased oxidative stress and cognitive impairment also occur together in many neurodegenerative conditions the therapeutic potential of NRF2 activating agents may extend beyond healthy aging.
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Persistent Identifier
https://archives.pdx.edu/ds/psu/28617
Included in
Loss of NRF2 results in decreased neuronal arborization and synaptic density and causes exacerbated age-related cognitive impairment.
Portland State University
Background: As the brain ages, free radicals accumulate and cause damage to cellular macromolecules. This increased oxidative damage is thought to contribute to the cognitive decline observed in aging. Activation of the antioxidant regulatory transcription factor NRF2 (Nuclear factor erythroid-derived 2) has been shown to improve neuronal health in aging and neurodegenerative diseases. Yet exactly how NRF2 participates in maintaining synaptic and cognitive function has not been fully elucidated. This study investigates how loss of NRF2 affects synaptic density and cognitive performance in aged mice.
Methods: Dendritic arborization and synaptic was evaluated in hippocampal neurons isolated from mice lacking NRF2 (NRF2KO) and from wild-type (WT) C57BL6 mice. Mitochondrial function of these neurons was evaluated using the Seahorse XF platform. Hippocampal and cortical expression of synaptic genes were measured.
Results: NRF2KO neurons had significantly reduced dendritic complexity relative to WT neurons as well as reduced synaptic gene expression. Similar deficits in synaptic gene expression were observed in the brains of aged NRF2KO mice relative to WT mice.
Conclusions: These data point to a role for NRF2 in maintaining synaptic health and cognitive function during aging and suggest that the transcription factor may be a viable target for cognitive enhancing interventions. Because increased oxidative stress and cognitive impairment also occur together in many neurodegenerative conditions the therapeutic potential of NRF2 activating agents may extend beyond healthy aging.