Selective Vulnerability of the Locus Coeruleus Noradrenergic System and its Role in Modulation of Neuroinflammation, Cognition, and Neurodegeneration

Locus coeruleus (LC) noradrenergic (NE) neurons supply the main adrenergic input to the forebrain. NE is a dual modulator of cognition and neuroinflammation. NE neurons of the LC are particularly vulnerable to degeneration both with normal aging and in neurodegenerative disorders. Consequences of th...

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Published inFrontiers in pharmacology Vol. 13; p. 1030609
Main Authors Evans, Andrew K., Defensor, Erwin, Shamloo, Mehrdad
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 30.11.2022
Subjects
beta-adrenergic
locus coeruleus
neurodegeneration
neuroinflammation
noradrenaline
oxidative stress
Pharmacology
Alzheimer’s disease
neuroinflammation
neurodegeneration
noradrenaline
beta-adrenergic
locus coeruleus
oxidative stress
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Summary:Locus coeruleus (LC) noradrenergic (NE) neurons supply the main adrenergic input to the forebrain. NE is a dual modulator of cognition and neuroinflammation. NE neurons of the LC are particularly vulnerable to degeneration both with normal aging and in neurodegenerative disorders. Consequences of this vulnerability can be observed in both cognitive impairment and dysregulation of neuroinflammation. LC NE neurons are pacemaker neurons that are active during waking and arousal and are responsive to stressors in the environment. Chronic overactivation is thought to be a major contributor to the vulnerability of these neurons. Here we review what is known about the mechanisms underlying this neuronal vulnerability and combinations of environmental and genetic factors that contribute to confer risk to these important brainstem neuromodulatory and immunomodulatory neurons. Finally, we discuss proposed and potential interventions that may reduce the overall risk for LC NE neuronal degeneration.
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Saeed Semnanian, Tarbiat Modares University, Iran
Edited by: Marta P. Pereira, Spanish National Research Council (CSIC), Spain
This article was submitted to Neuropharmacology, a section of the journal Frontiers in Pharmacology
Reviewed by: Jason Langley, University of California, Riverside, United States
ISSN:1663-9812
1663-9812
DOI:10.3389/fphar.2022.1030609