Norepinephrine as a modulator of microglial dynamics

Mercan, Dilek; Heneka, Michael T.

doi:10.1038/s41593-019-0526-9

Cited by 8 publications

(11 citation statements)

References 15 publications

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“…18 It is worth noting that NE also reduces the contact area between microglia and neuron dendrites and their direct contact time, thereby reducing the neuronal damage. 13 This evidence indicates that the realtime monitoring of CNS by microglia is regulated by NE.…”

Section: Ne Affects the Surveillance Function Of Microglia In The Brain Parenchymal Functionmentioning

confidence: 89%

“…It has been reported that the levels of acetylcholine (Ach), dopamine, serotonin, and NE are reduced during general anesthesia; in addition, compared with awake mice, the microglia of anesthetized mice have an enhanced immune response to injury 14 . Mercan et al administered these neuromodulators to the brains of mice under isoflurane anesthesia and found that only NE can prevent anesthesia induction from affecting microglia 13 . Cao et al compared the microglial neuroinflammation in APP/PS1 mice and aging mice, and the degree of degenerative changes in the LC–NE system, and found that compared with aging mice, the activation of microglia in the spinal cord of APP/PS1 mice is increased, the expression of proinflammatory cytokines is upregulated, and the projection of NE neurons is reduced.…”

Section: Ne Regulates Inflammatory Activation Of Microgliamentioning

confidence: 99%

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Effects of norepinephrine on microglial neuroinflammation and neuropathic pain

Zou

Zhou

et al. 2021

Ibrain

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Norepinephrine (NE) is an important neurotransmitter in the central nervous system. NE is released from locus coeruleus neurons and is involved in a variety of physiological and pathological processes. Neuroinflammation is a common manifestation of many kinds of neurological diseases. The activation of microglia directly affects the status of neuroinflammation. Several kinds of adrenergic receptors, which anchor on microglia and can be regulated by NE, affect the activation of microglia and neuroinflammation. NE influences chronic pain, anxiety, and depression by regulating the activation of microglia.

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Section: Ne Affects the Surveillance Function Of Microglia In The Brain Parenchymal Functionmentioning

confidence: 89%

Section: Ne Regulates Inflammatory Activation Of Microgliamentioning

confidence: 99%

Effects of norepinephrine on microglial neuroinflammation and neuropathic pain

Zou

Zhou

et al. 2021

Ibrain

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“…As the literature is evolving rapidly the points of intersection between VNS and brain waste clearance is constantly growing. Beyond the effects already mentioned these interactions potentially include VNS-induced intrinsic brain oscillations, effects on the blood-brain barrier, and direct and indirect effects on glial cell activity function [21,25,26]. Thus, isolating each possible variable will likely involve a large and lengthy multi-disciplinary effort to both identify the mechanisms involved as well as optimize stimulation parameters for maximal beneficial effect.…”

Section: Discussionmentioning

confidence: 99%

Clinically-derived vagus nerve stimulation enhances cerebrospinal fluid penetrance

et al. 2020

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Introduction: Vagus nerve stimulation (VNS) is an FDA-approved neuromodulatory treatment used in the clinic today for epilepsy, depression, and cluster headaches. Moreover, evidence in the literature has led to a growing list of possible clinical indications, with several small clinical trials applying VNS to treat conditions ranging from neurodegenerative diseases to arthritis, anxiety disorders, and obesity. Despite the growing list of therapeutic applications, the fundamental mechanisms by which VNS achieves its beneficial effects are poorly understood. In parallel, the glymphatic and meningeal lymphatic systems have recently been described as methods by which the brain maintains a healthy homeostasis and removes waste without a traditionally defined lymphatic system. In particular, the glymphatic system relates to the interchange of cerebrospinal fluid (CSF) and interstitial fluid (ISF) whose net effect is to wash through the brain parenchyma removing metabolic waste products and misfolded proteins. Objective/Hypothesis: As VNS has well-documented effects on many of the pathways recently linked to the clearance systems of the brain, we hypothesized that VNS could increase CSF penetrance in the brain. Methods: We injected a low molecular weight lysine-fixable fluorescent tracer (TxRed-3kD) into the CSF system of mice with a cervical vagus nerve cuff implant and measured the amount of CSF penetrance following an application of a clinically-derived VNS paradigm (30 Hz, 10% duty cycle). Results: We found that the clinical VNS group showed a significant increase in CSF tracer penetrance as compared to the naïve control and sham groups. Conclusion: (s):This study demonstrates that VNS therapeutic strategies already being applied in the clinic today may induce intended effects and/or unwanted side effects by altering CSF/ISF exchange in the brain. This may have broad ranging implications in the treatment of various CNS pathologies.

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“…Using two-photon laser scanning in vivo microscopy of CX3CR1-EGFP mice, two more recent studies advanced our knowledge further by showing that awake and anesthetized conditions may influence microglial dynamics [ 178 , 179 , 180 ]. It is well-known that LC terminals release NA in order to promote wakefulness.…”

Section: The Locus Coeruleus–noradrenaline System and Microgliamentioning

confidence: 99%

“…The two studies illustrated, by using in vivo imaging, that NA reduces microglial arborization, surveillance, and injury response through the β2-adrenergic receptors. Additionally, NA also reduces the amount of time and contact areas that microglia spend with neuronal dendrites [ 178 , 179 , 180 ]. For instance, dexmedetomidine (DEX), which acts as a sedative by reducing NA release from the LC, enhanced microglial arborization and surveillance; however, optogenetic stimulation of the LC by channelrhodopsin led to reductions in process surveillance dynamics in DEX treated mice [ 179 ].…”

Section: The Locus Coeruleus–noradrenaline System and Microgliamentioning

confidence: 99%

The Contribution of the Locus Coeruleus–Noradrenaline System Degeneration during the Progression of Alzheimer’s Disease

Mercan

Heneka

2022

Biology

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Alzheimer’s disease (AD), which is characterized by extracellular accumulation of amyloid-beta peptide and intracellular aggregation of hyperphosphorylated tau, is the most common form of dementia. Memory loss, cognitive decline and disorientation are the ultimate consequences of neuronal death, synapse loss and neuroinflammation in AD. In general, there are many brain regions affected but neuronal loss in the locus coeruleus (LC) is one of the earliest indicators of neurodegeneration in AD. Since the LC is the main source of noradrenaline (NA) in the brain, degeneration of the LC in AD leads to decreased NA levels, causing increased neuroinflammation, enhanced amyloid and tau burden, decreased phagocytosis and impairment in cognition and long-term synaptic plasticity. In this review, we summarized current findings on the locus coeruleus–noradrenaline system and consequences of its dysfunction which is now recognized as an important contributor to AD progression.

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Norepinephrine as a modulator of microglial dynamics

Cited by 8 publications

References 15 publications

Effects of norepinephrine on microglial neuroinflammation and neuropathic pain

Effects of norepinephrine on microglial neuroinflammation and neuropathic pain

Clinically-derived vagus nerve stimulation enhances cerebrospinal fluid penetrance

The Contribution of the Locus Coeruleus–Noradrenaline System Degeneration during the Progression of Alzheimer’s Disease

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