Viral Vector-Mediated Upregulation of Serine Racemase Expression

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Aging (Aging-US)

Aging-US published this research paper on April 12, 2023 in Volume 15, Issue 7, entitled, "Viral vector-mediated upregulation of serine racemase expression in medial prefrontal cortex improves learning and synaptic function in middle age rats" by researchers from the Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, FL. DOI - https://doi.org/10.18632/aging.204652 Corresponding author - Ashok Kumar - kash@ufl.edu Abstract An age-associated decrease in N-methyl-D-aspartate receptor (NMDAR)-mediated synaptic function contributes to impaired synaptic plasticity and is associated with cognitive impairments. Levels of serine racemase (SR), an enzyme that synthesizes D-serine, an NMDAR co-agonist, decline with age. Thus, enhancing NMDAR function via increased SR expression in middle age, when subtle declines in cognition emerge, was predicted to enhance performance on a prefrontal cortex-mediated task sensitive to aging. Middle-aged (~12 mo) male Fischer-344 rats were injected bilaterally in the medial prefrontal cortex (mPFC) with viral vector (LV), SR (LV-SR) or control (LV-GFP). Rats were trained on the operant attentional set-shift task (AST) to examine cognitive flexibility and attentional function. LV-SR rats exhibited a faster rate of learning compared to controls during visual discrimination of the AST. Extradimensional set shifting and reversal were not impacted. Immunohistochemical analyses demonstrated that LV-SR significantly increased SR expression in the mPFC. Electrophysiological characterization of synaptic transmission in the mPFC slices obtained from LV-GFP and LV-SR animals indicated a significant increase in isolated NMDAR-mediated synaptic responses in LV-SR slices. Thus, results of the current study demonstrated that prefrontal SR upregulation in middle age rats can improve learning of task contingencies for visual discrimination and increase glutamatergic synaptic transmission, including NMDAR activity. Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204652 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, medial prefrontal cortex, serine racemase, D-serine, NMDA receptor, cognitive flexibility 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 https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM