ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Prefrontal cortical GABAergic dysfunction contributes to age-related working memory impairment.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
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Who cites it
89 citing papers in PubMed, 138 citations in OpenAlex.
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- Role of the STING→IRF3 Pathway in Ambient GABA Homeostasis and Cognitive Function.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Working Memory Performance Predicts, but Does Not Reduce, Cocaine and Cannabinoid Seeking in Adult Male Rats.The international journal of neuropsychopharmacology · 2024Article
- Mitigation of aging-related plasticity decline through taurine supplementation and environmental enrichment.Scientific reports · 2024Article
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- Intermittent working memory training during adulthood protects against age-related long-term spatial reference memory decline in rats.GeroScience · 2024Article
- The role of the GABAergic cells of the median raphe region in reinforcement-based learning.Scientific reports · 2024Article
- Toxicological landscape of Fuzi: a comprehensive study on the spatial distribution of toxicants and regional neurotoxicity variability in zebrafish.Frontiers in pharmacology · 2024Article
- Adipose Tissue Exosome circ_sxc Mediates the Modulatory of Adiposomes on Brain Aging by Inhibiting Brain dme-miR-87-3p.Molecular neurobiology · 2024Article
- Expression of GAD65/67 and VGLUT2 in Mediobasal Nuclei of Rat Hypothalamus during Aging.Bulletin of experimental biology and medicine · 2023Article
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- Cognitive mechanisms underlying decision making involving risk of explicit punishment in male and female rats.Cognitive, affective & behavioral neuroscience · 2023Article
29 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Working memory functions supported by the prefrontal cortex decline in normal aging. Disruption of corticolimbic GABAergic inhibitory circuits can impair working memory in young subjects; however, relatively little is known regarding how aging impacts prefrontal cortical GABAergic signaling and whether such changes contribute to cognitive deficits. The current study used a rat model to evaluate the effects of aging on expression of prefrontal GABAergic synaptic proteins in relation to working memory decline, and to test whether pharmacological manipulations of prefrontal GABAergic signaling can improve working memory abilities in aged subjects. Results indicate that in aged medial prefrontal cortex (mPFC), expression of the vesicular GABA transporter VGAT was unchanged; however, there was a significant increase in expression of the GABA synthesizing enzyme GAD67, and a significant decrease in the primary neuronal GABA transporter GAT-1 and in both subunits of the GABA(B) receptor (GABA(B)R). Expression of VGAT, GAD67, and GAT-1 was not associated with working memory ability. In contrast, among aged rats, GABA(B)R expression was significantly and negatively associated with working memory performance, such that lower GABA(B)R expression predicted better working memory. Subsequent experiments showed that systemic administration of a GABA(B)R antagonist, CGP55845, dose-dependently enhanced working memory in aged rats. This enhancing effect of systemic CGP55845 was reproduced by direct intra-mPFC administration. Together, these data suggest that age-related dysregulation of GABAergic signaling in prefrontal cortex may play a causal role in impaired working memory and that targeting GABA(B)Rs may provide therapeutic benefit for age-related impairments in executive functions.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.