ArticleAging cell2025
Aging disrupts locus coeruleus-driven norepinephrine transmission in the prefrontal cortex: Implications for cognitive and motor decline.
Article in Aging cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- The monoaminergic systems as drivers of Alzheimer's disease pathophysiology and symptomatology.Current opinion in neurology · 2026Review
- A locus coeruleus-centric framework for novelty, salience, and gamma oscillations: implications for neurostimulation, aging, and disease.Frontiers in aging neuroscience · 2026Article
- The rise and deceleration of neuronal excitability in aging and Alzheimer's disease: Mechanisms, implications, and therapeutic targets.Ageing research reviews · 2026Review
- Article
- The Locus Coeruleus-Noradrenergic System in the Healthy and Diseased Brain: A Narrative Review.European journal of neurology · 2025Review
- Age-Related Increase in Locus Ceruleus Activity and Connectivity with the Prefrontal Cortex during Ambiguity Processing.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- NDUFA10-Mediated ATP Reduction in Medial Prefrontal Cortex Exacerbates Burst Suppression in Aged Mice.CNS neuroscience & therapeutics · 2025Article
- Early signs of neuron autonomous and non-autonomous hyperexcitability in locus coeruleus noradrenergic neurons of a mouse model of tauopathy and Alzheimer's disease.Acta physiologica (Oxford, England) · 2025Article
- Aging disrupts locus coeruleus-driven norepinephrine transmission in the prefrontal cortex: Implications for cognitive and motor decline.Aging cell · 2025Article
- Diversity of ancestral brainstem noradrenergic neurons across species and multiple biological factors.bioRxiv : the preprint server for biology · 2024Article
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Authors and funding
9 authors.
Funding
Abstract
The locus coeruleus (LC)-prefrontal cortex (PFC) circuitry is crucial for cognition, planning, posture and mobility. This study examines the role of norepinephrine (NE) in elucidating the neurobiological basis of age-related cognitive and motor declines. Aged mice exhibited reduced spatial learning, impaired memory, decreased physical endurance, and notable changes in locomotor behavior. The neurochemical foundations of these deficits were investigated through fast-scan cyclic voltammetry to measure NE release in the PFC and LC, both in vivo and in brain slices. Additionally, oxygen levels were monitored as a proxy for PFC neuronal function, and NE levels were analyzed in the extracellular space via microdialysis and total content in the PFC. Aged mice exhibited a frequency-dependent increase in NE release in the PFC upon LC stimulation, suggesting alterations in neural responsiveness due to aging. We also recorded slower NE reuptake rates and increased NE content and neuronal activity, indicated by higher oxygen levels and facilitated neuron activation due to membrane depolarization recorded via whole-cell patch-clamp. To understand the basis for LC-driven NE surges in the PFC with aging, we examined the expression levels of two proteins critical for presynaptic NE release and NE reuptake: the α2a-adrenergic receptor and the NE transporter. Both showed a significant decrease in the PFC with aging. These findings support the concept that aging significantly alters the structural and functional dynamics within the LC-PFC neural circuit, impacting NE modulation and neuronal activity, which may underlie the observed declines in cognitive and motor functions in aging populations.
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