Isoform-Specific Effects of Neuronal Repression of AMPK Catalytic Subunit on Cognitive Function



March 6, 2023

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  • Aging-US published this research paper in Volume 15, Issue 4, entitled, "Isoform-specific effects of neuronal repression of the AMPK catalytic subunit on cognitive function in aged mice" by researchers from the Department of Internal Medicine-Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Winston-Salem, NC; Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC; Department of Neurobiology and Anatomy, Wake Forest University School of Medicine, Winston-Salem, NC. DOI - Corresponding author - Tao Ma - Abstract AMP-activated protein kinase (AMPK) functions as a molecular sensor that plays a critical role in maintaining cellular energy homeostasis. Dysregulation of the AMPK signaling has been linked to synaptic failure and cognitive impairments. Our recent study demonstrates abnormally increased AMPK activity in the hippocampus of aged mice. The kinase catalytic subunit of AMPK exists in two isoforms α1 and α2, and their specific roles in aging-related cognitive deficits are unknown. Taking advantage of the unique transgenic mice (AMPKα1/α2 cKO) recently developed by our group, we investigated how isoform-specific suppression of the neuronal AMPKα may contribute to the regulation of cognitive and synaptic function associated with aging. We found that aging-related impairment of long-term object recognition memory was improved with suppression of AMPKα1 but not AMPKα2 isoform. Moreover, aging-related spatial memory deficits were unaltered with suppression of either AMPKα isoform. Biochemical experiments showed that the phosphorylation levels of the eukaryotic initiation factor 2 α subunit (eIF2α) were specifically decreased in the hippocampus of the AMPKα1 cKO mice. We further performed large-scale unbiased proteomics analysis and revealed identities of proteins whose expression is differentially regulated with AMPKα isoform suppression. These novel findings may provide insights into the roles of AMPK signaling pathway in cognitive aging. Sign up for free Altmetric alerts about this article - Keywords - AMPK, aging, protein synthesis, learning and memory, proteomics About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at​​ and connect with us: SoundCloud - Facebook - Twitter - Instagram - YouTube - LinkedIn - Pinterest - Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

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