Noradrenergic neuromodulation in ageing and disease

The locus coeruleus (LC) is a small brainstem structure located in the lower pons and is the main source of noradrenaline (NA) in the brain. Via its phasic and tonic firing, it modulates cognition and autonomic functions and is involved in the brain’s immune response. The extent of degeneration to t...

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Bibliographic Details
Published in:Neuroscience and biobehavioral reviews 2023-09, Vol.152, p.105311, Article 105311
Main Authors: Krohn, F., Lancini, E., Ludwig, M., Leiman, M., Guruprasath, G., Haag, L., Panczyszyn, J., Düzel, E., Hämmerer, D., Betts, M.
Format: Article
Language:English
Subjects:
Alzheimer Disease - pathology
Brain - pathology
Brain Stem - pathology
Humans
Locus coeruleus
Locus Coeruleus - physiology
Noradrenaline
Noradrenergic neuromodulation
Norepinephrine
Parkinson Disease - pathology
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Summary:The locus coeruleus (LC) is a small brainstem structure located in the lower pons and is the main source of noradrenaline (NA) in the brain. Via its phasic and tonic firing, it modulates cognition and autonomic functions and is involved in the brain’s immune response. The extent of degeneration to the LC in healthy ageing remains unclear, however, noradrenergic dysfunction may contribute to the pathogenesis of Alzheimer’s (AD) and Parkinson’s disease (PD). Despite their differences in progression at later disease stages, the early involvement of the LC may lead to comparable behavioural symptoms such as preclinical sleep problems and neuropsychiatric symptoms as a result of AD and PD pathology. In this review, we draw attention to the mechanisms that underlie LC degeneration in ageing, AD and PD. We aim to motivate future research to investigate how early degeneration of the noradrenergic system may play a pivotal role in the pathogenesis of AD and PD which may also be relevant to other neurodegenerative diseases. •LC integrity, structural and functional connectivity are linked to age-related cognitive decline.•LC degeneration in AD and PD may be regionally specific and is linked to a decline in noradrenergic functions.•NA and its metabolism is dysregulated in AD and PD.•NA drugs, vagus nerve stimulation and physical exercise show promisee as therapeutic targets for NA dysfunction
ISSN:0149-7634
1873-7528
1873-7528
DOI:10.1016/j.neubiorev.2023.105311