Ageing neuroinflammation and neurodegeneration

Leontovich, Alexey A.; Dronca, Roxana S.; Suman, Vera J.; Ashdown, Martin; Nevala, Wendy K.; Thompson, Michael A.; Robinson, Andrew; Kottschade, Lisa A.; Kaur, Judith S.; McWilliams, Robert R.; Іванов, Л. В.; Croghan, Gary A.; Markovic, Svetomir N.

doi:10.2741/433

Cited by 22 publications

(10 citation statements)

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“…Recent studies have confirmed that neuroinflammation plays a critical role in the pathogenesis of neurodegenerative diseases, including PD [22,23,24,25]. Neuroinflammatory mechanisms might contribute to a cascade of events that result in the progressive degeneration and/or death of neuron cells in PD [22].…”

Section: Discussionmentioning

confidence: 99%

GPER Agonist G1 Attenuates Neuroinflammation and Dopaminergic Neurodegeneration in Parkinson Disease

Guan

Yang

Fan

et al. 2017

Neuroimmunomodulation

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Objective: Epidemiological studies have shown that women of reproductive age have much less possibility of developing Parkinson disease (PD) than men. The beneficial effect of estrogen also has been well-described in both culture and animal models of PD. G protein-coupled estrogen receptor (GPER) is a membrane-associated estrogen receptor, and displayed a neuroprotective role in a mouse model of PD. Since GPER is highly expressed in microglia, we speculate that GPER mediates the neuroprotective function of estradiol through suppressing the neuroinflammation of PD. Methods: We investigated the effects of GPER agonist G1 and GPER antagonist G15 on the neurodegeneration of dopaminergic neuron, the activation of microglia, and the production of IL-1β, TNF-α, and IL-6 in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced animal model of parkinsonism. Furthermore, we confirmed the effects of GPER activation on the production of IL-1β, TNF-α, and IL-6 in an in vitro MPP+ model in BV2 microglial cells. Results: After 12-day treatment with G1, mice showed an increase in the number of tyrosine hydroxylase-immunoreactive cells, reduced activation of microglia, and the abatement of proinflammatory cytokines, and the anti-inflammatory effect of G1 was abolished by G15. Meanwhile, in vitro studies demonstrated that GPER activation also reduced the release of proinflammatory cytokines from BV2 microglial cells after MPP+ stimulation. Conclusion: Our data suggest that GPER mediates the anti-neuroinflammatory effect of estrogen in experimental PD progression.

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Section: Discussionmentioning

confidence: 99%

GPER Agonist G1 Attenuates Neuroinflammation and Dopaminergic Neurodegeneration in Parkinson Disease

Guan

Yang

Fan

et al. 2017

Neuroimmunomodulation

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“…Alzheimer's disease (AD) and motor neurone disease (MND) are two common neurodegenerative disorders which are characterized by the progressive loss of structure and function of neurons in the aging population (Ward et al., 2015). Numerous commonalities have been identified across genetics, pathology, and cellular mechanisms in these diseases.…”

Section: Introductionmentioning

confidence: 99%

Normal aging, motor neurone disease, and Alzheimer’s disease are characterized by cortical changes in inflammatory cytokines

Tennakoon

Katharesan

Musgrave

et al. 2021

J of Neuroscience Research

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The role of increased brain inflammation in the development of neurodegenerative diseases is unclear. Here, we have compared cytokine changes in normal aging, motor neurone disease (MND), and Alzheimer's disease (AD). After an initial analysis, six candidate cytokines, interleukin (IL)-4, 5, 6, 10, macrophage inhibitory protein (MIP)-1α, and fibroblast growth factor (FGF)-2, showing greatest changes were assayed in postmortem frozen human superior frontal gyri (n = 12) of AD patients, aging and young adult controls along with the precentral gyrus (n = 12) of MND patients. Healthy aging was associated with decreased anti-inflammatory IL-10 and FGF-2 levels. AD prefrontal cortex was associated with increased levels of IL-4, IL-5, and FGF-2, with the largest increase seen for FGF-2. Notwithstanding differences in the specific frontal lobe gyrus sampled, MND patients' primary motor cortex (precentral gyrus) was associated with increased levels of IL-5, IL-6, IL-10, and FGF-2 compared to the aging prefrontal cortex (superior frontal gyrus). Immunocytochemistry showed that FGF-2 is expressed in neurons, astrocytes, and microglia in normal aging prefrontal cortex, AD prefrontal cortex, and MND motor cortex. We report that healthy aging and agerelated neurodegenerative diseases have different cortical inflammatory signatures that are characterized by increased levels of anti-inflammatory cytokines and call into question the view that increased inflammation underlies the development of agerelated neurodegenerative diseases.

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“…Neuroinflammation is well-documented to be a part of the neuropathogenesis of a cognitive deficit. 1,2 The elderly show vulnerability to the detrimental effects of infections on cognition, and the aging process itself is closely correlated with augmented neuroinflammatory response, including the production of pro-inflammatory cytokines and the imbalance of microglial M1/M2 polarization. 3 Neuroinflammation also occurs in the brain of patients with Alzheimer's disease (AD).…”

Section: ■ Introductionmentioning

confidence: 99%

Geraniin Attenuates Lipopolysaccharide-Induced Cognitive Impairment in Mice by Inhibiting Toll-Like Receptor 4 Activation

Wang

Dong

Wang

et al. 2019

J. Agric. Food Chem.

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Geraniin has been reported to possess potent anti-inflammatory properties and to modulate the macrophage polarization. This study sought to evaluate the protective effects and underlying mechanisms of geraniin on lipopolysaccharide (LPS)-induced neuroinflammation and neurobiological alternations as well as cognitive impairment. Daily intragastrical administration with geraniin (20 mg kg–1 day–1) for 14 days significantly prolonged the duration in the target quadrant (26.53 ± 2.03 versus 37.09 ± 3.27%; p < 0.05) and increased crossing-target number (1.93 ± 0.22 versus 3.08 ± 0.17; p < 0.01) in the probe test of LPS-treated mice. Geraniin also ameliorated LPS-elicited neural/synaptic impairments and decreased levels of LPS-induced Aβ generation (p < 0.05), amyloid precursor protein (APP) (p < 0.05) and β-site amyloid precursor protein cleavage enzyme 1 (BACE1) (p < 0.05). Furthermore, geraniin suppressed the production of pro-inflammatory cytokines, including tumor necrosis factor α (TNF-α) (9.85 ± 0.58 versus 5.20 ± 0.52 pg/mg of protein; p < 0.01), interleukin (IL)-1β (16.31 ± 0.67 versus 8.62 ± 0.46 pg/mg of protein; p < 0.01), and IL-6 (12.12 ± 0.45 versus 7.43 ± 0.32 pg/mg of protein; p < 0.05), and inhibited glial cell activation. Moreover, geraniin effectively polarized the microglia toward an anti-inflammatory M2 phenotype. Further study revealed that geraniin targeted toll-like receptor 4 (TLR4)-mediated signaling and decreased the production of pro-inflammatory cytokines in BV-2 microglial cells. These results indicate that geraniin mitigates LPS-elicited neural/synaptic neurodegeneration, amyloidogenesis, neuroinflammation, and cognitive impairment and suggest geraniin as a therapeutic option for neuroinflammation-associated neurological disorders, such as Alzheimer’s disease.

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Ageing neuroinflammation and neurodegeneration

Cited by 22 publications

References 0 publications

GPER Agonist G1 Attenuates Neuroinflammation and Dopaminergic Neurodegeneration in Parkinson Disease

GPER Agonist G1 Attenuates Neuroinflammation and Dopaminergic Neurodegeneration in Parkinson Disease

Normal aging, motor neurone disease, and Alzheimer’s disease are characterized by cortical changes in inflammatory cytokines

Geraniin Attenuates Lipopolysaccharide-Induced Cognitive Impairment in Mice by Inhibiting Toll-Like Receptor 4 Activation

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