Causes, consequences, and cures for neuroinflammation mediated via the locus coeruleus: noradrenergic signaling system

@article{Feinstein2016CausesCA,
  title={Causes, consequences, and cures for neuroinflammation mediated via the locus coeruleus: noradrenergic signaling system},
  author={Douglas L. Feinstein and Sergey Kalinin and David Braun},
  journal={Journal of Neurochemistry},
  year={2016},
  volume={139}
}
Aside from its roles in as a classical neurotransmitter involved in regulation of behavior, noradrenaline (NA) has other functions in the CNS. This includes restricting the development of neuroinflammatory activation, providing neurotrophic support to neurons, and providing neuroprotection against oxidative stress. In recent years, it has become evident that disruption of physiological NA levels or signaling is a contributing factor to a variety of neurological diseases and conditions including… 

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References

SHOWING 1-10 OF 297 REFERENCES

Noradrenergic Regulation of Glial Activation: Molecular Mechanisms and Therapeutic Implications

TLDR
Methods to increase NA levels, or to reduce damage to noradrenergic neurons, therefore represent potential preventative as well as therapeutic approaches to disease.

Increasing CNS Noradrenaline Reduces EAE Severity

TLDR
The data suggest that selective elevation of CNS NA levels could provide benefit in EAE and multiple sclerosis without influencing peripheral immune responses.

Locus coeruleus damage and noradrenaline reductions in multiple sclerosis and experimental autoimmune encephalomyelitis.

TLDR
The presence of inflammation and neuronal stress in multiple sclerosis as well as in experimental autoimmune encephalomyelitis is demonstrated and methods to raise noradrenaline levels or increase locus coeruleus function may be of benefit in treating multiple sclerosis.

A noradrenergic lesion exacerbates neurodegeneration in a Down syndrome mouse model.

TLDR
It is suggested that noradrenergic degeneration may play a role in the progressive memory loss, neuroinflammation, and cholinergic loss occurring in DS individuals, providing a possible therapeutic avenue for future clinical studies.

Norepinephrine Protects against Amyloid-β Toxicity via TrkB.

TLDR
It is reported that NE dose-dependently protected primary cortical and LC neurons from amyloid-β (Aβ) toxicity and indicate that NE can activate TrkB and protect against Aβ toxicity, at least in part, via adrenergic receptor-independent mechanisms.

Norepinephrine Protects against Amyloid-beta Toxicity via TrkB

TLDR
It is reported that NE dosedependently protected primary cortical and LC neurons from amyloid-β (Aβ) toxicity and have implications for the consequences of LC degeneration in AD and potential therapies for the disease.

Noradrenaline reuptake inhibitors limit neuroinflammation in rat cortex following a systemic inflammatory challenge: implications for depression and neurodegeneration.

TLDR
It is demonstrated that acute treatment of rats with the noradrenaline reuptake inhibitors desipramine and atomoxetine elicited anti-inflammatory actions in rat cortex following a systemic challenge with bacterial lipopolysaccharide, and these results suggest that in vivo administration of NRIs limit inflammatory events in the brain, probably by increasing nor adrenaline availability.

Noradrenergic Depletion Potentiates β-Amyloid-Induced Cortical Inflammation: Implications for Alzheimer's Disease

TLDR
It is demonstrated that LC loss and NE depletion augment inflammatory responses to Aβ and suggest that LC lost in AD is permissive for increased inflammation and neuronal cell death.

Noradrenergic depletion increases inflammatory responses in brain: effects on IκB and HSP70 expression

TLDR
It is suggested that noradrenergic depletion reduces levels of anti‐inflammatory molecules which normally limit cortical responses to Aβ, and that PPARγ agonists can reverse that effect.
...