ArticleeNeuro
Age-Related Declines in Prefrontal Cortical Expression of Metabotropic Glutamate Receptors that Support Working Memory.
Article in eNeuro. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 67 citations in OpenAlex.
- Inflammatory mechanisms underlying early Alzheimer's disease pathology: evidence from the aging rhesus macaque brain.Frontiers in cellular neuroscience · 2026Review
- Post-methamphetamine working memory decline predicts relapse vulnerability in rats and is rescued by mGlu3 receptor activation.Psychopharmacology · 2026Article
- Network-level organization of systemic inflammation reflects early Alzheimer's-like behavioral changes.Scientific reports · 2025Article
- Network-Level Organization of Systemic Inflammation Reflects Early Alzheimer's-Like Behavioral Changes.Research square · 2025Article
- Ketogenic Diet-Induced Alterations in Neuronal Signaling-Related Proteins are Not Due to Differences in Synaptosome Protein Levels.Molecular neurobiology · 2025Article
- Expression of group II mGluRs in the inferior colliculus, medial geniculate body, and auditory cortex increases with age.Neuroscience · 2025Article
- Aberrant glutamatergic systems underlying impulsive behaviors: Insights from clinical and preclinical research.Progress in neuro-psychopharmacology & biological psychiatry · 2024Review
- In a circuit necessary for cognition and emotional affect, Alzheimer's-like pathology associates with neuroinflammation, cognitive and motivational deficits in the young adult TgF344-AD rat.Brain, behavior, & immunity - health · 2024Article
- Hippocampal astrocytes induce sex-dimorphic effects on memory.Cell reports · 2024Article
- Glycine Transporter 1 Inhibitors: Predictions on Their Possible Mechanisms in the Development of Opioid Analgesic Tolerance.Biomedicines · 2024Review
- Localization of PDE4D, HCN1 channels, and mGluR3 in rhesus macaque entorhinal cortex may confer vulnerability in Alzheimer's disease.Cerebral cortex (New York, N.Y. : 1991) · 2023Article
- Aging or chronic stress impairs working memory and modulates GABA and glutamate gene expression in prelimbic cortex.Frontiers in aging neuroscience · 2023Article
- Metabotropic glutamate receptor 3 as a potential therapeutic target for psychiatric and neurological disorders.Pharmacology, biochemistry, and behavior · 2022Review
- GABANeuropharmacology · 2022Article
- Glutamate Metabotropic Receptor Type 3 (mGlu3) Localization in the Rat Prelimbic Medial Prefrontal Cortex.Frontiers in neuroanatomy · 2022Article
- Studies of aging nonhuman primates illuminate the etiology of early-stage Alzheimer's-like neuropathology: An evolutionary perspective.American journal of primatology · 2021Review
- Dynamic interplay of frontoparietal cholinergic innervation and cortical reorganization in the regulation of attentional capacities in aging.Neurobiology of aging · 2021Article
- Article
- Glutamate Carboxypeptidase II in Aging Rat Prefrontal Cortex Impairs Working Memory Performance.Frontiers in aging neuroscience · 2021Article
- Using rat operant delayed match-to-sample task to identify neural substrates recruited with increased working memory load.Learning & memory (Cold Spring Harbor, N.Y.) · 2020Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Glutamate signaling is essential for the persistent neural activity in prefrontal cortex (PFC) that enables working memory. Metabotropic glutamate receptors (mGluRs) are a diverse class of proteins that modulate excitatory neurotransmission via both presynaptic regulation of extracellular glutamate levels and postsynaptic modulation of ion channels on dendritic spines. This receptor class is of significant therapeutic interest for treatment of cognitive disorders associated with glutamate dysregulation. Working memory impairment and cortical hypoexcitability are both associated with advanced aging. Whether aging modifies PFC mGluR expression, and the extent to which any such alterations are regionally or subtype specific, however, is unknown. Moreover, it is unclear whether specific mGluRs in PFC are critical for working memory, and thus, whether altered mGluR expression in aging or disease is sufficient to play a causative role in working memory decline. Experiments in the current study first evaluated the effects of age on medial PFC (mPFC) mGluR expression using biochemical and molecular approaches in rats. Of the eight mGluRs examined, only mGluR5, mGluR3, and mGluR4 were significantly reduced in the aged PFC. The reductions in mGluR3 and mGluR5 (but not mGluR4) were observed in both mRNA and protein and were selectively localized to the prelimbic (PrL), but not infralimbic (IL), subregion of mPFC. Finally, pharmacological blockade of mGluR5 or mGluR2/3 using selective antagonists directed to PrL significantly impaired working memory without influencing non-mnemonic aspects of task performance. Together, these data implicate attenuated expression of PFC mGluR5 and mGluR3 in the impaired working memory associated with advanced ages.
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Registered trials
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.