M2 Macrophage Transplantation Ameliorates Cognitive Dysfunction in Amyloid-β-Treated Rats Through Regulation of Microglial Polarization

Zhu, Dan; Yang, Nan; Liu, Y; Zheng, Jie; Ji, Chao; Zuo, Pingping

doi:10.3233/jad-151090

Cited by 73 publications

(58 citation statements)

References 57 publications

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“…These findings suggested that the protective effect might may in part due to the reduced number of M1 cells. M2 macrophages/microglia function as an anti-inflammatory subset, expressing high levels of cytokines such as IL-10 and TGF-β, as well as neurotrophic factors such as nerve growth factor (NGF) 50 and insulin-like growth factor-1 (IGF-1) 51 . These beneficial cytokine and neurotrophic factors participate in neuronal protection and survival.…”

Section: Discussionmentioning

confidence: 99%

Low-level laser facilitates alternatively activated macrophage/microglia polarization and promotes functional recovery after crush spinal cord injury in rats

Song

Liang

et al. 2017

Sci Rep

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Macrophages and resident microglia play an import role in the secondary neuroinflammation response following spinal cord injury. Reprogramming of macrophage/microglia polarization is an import strategy for spinal cord injury restoration. Low-level laser therapy (LLLT) is a noninvasive treatment that has been widely used in neurotrauma and neurodegenerative diseases. However, the influence of low-level laser on polarization of macrophage/microglia following spinal cord injury remains unknown. The present study applied low-level laser therapy on a crush spinal cord injury rat model. Using immunofluorescence, flow cytometry, RT-qPCR, and western blot assays, we found that low-level laser therapy altered the polarization state to a M2 tendency. A greater number of neurons survived in the pare injury site, which was accompanied by higher BBB scores in the LLLT group. Furthermore, low-level laser therapy elevated expression of interleukin 4 (IL-4) and interleukin 13 (IL-13). Results from this study show that low-level laser therapy has the potential for reducing inflammation, regulating macrophage/microglia polarization, and promoting neuronal survival. These beneficial effects demonstrate that low-level laser therapy may be an effective candidate for clinical treatment of spinal cord injury.

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Section: Discussionmentioning

confidence: 99%

Low-level laser facilitates alternatively activated macrophage/microglia polarization and promotes functional recovery after crush spinal cord injury in rats

Song

Liang

et al. 2017

Sci Rep

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“…Clearance of Aβ and chronic inflammation are related to the polarization of and phagocytotic ability of microglia (Ide et al, 1996; Heese et al, 1998; Hutchinson et al, 2009; Tang and Le, 2016). The M2 phenotype microglia have been demonstrated to have a neuroprotective function in AD (Zhu et al, 2016). A recent study showed that M2 macrophage transplantation reduces neuroinflammation in the brain, promotes clearance of Aβ, and improves cognitive impairment (Zhu et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

“…The M2 phenotype microglia have been demonstrated to have a neuroprotective function in AD (Zhu et al, 2016). A recent study showed that M2 macrophage transplantation reduces neuroinflammation in the brain, promotes clearance of Aβ, and improves cognitive impairment (Zhu et al, 2016). Aβ and tau oligomers activate M1 pro-inflammatory responses and induce irreversible neuron loss (Tang and Le, 2016).…”

Section: Discussionmentioning

confidence: 99%

“…Numerous studies have suggested that microglia are activated in the AD brain and contribute to the prevention of Aβ formation through phagocytosis of Aβ (Rogers et al, 2002; Doens and Fernández, 2014). Several studies have demonstrated that M2 type microglia reduce inflammation in the brain (Weekman et al, 2014; Latta et al, 2015) and ameliorate cognitive dysfunction during Aβ toxicity (Zhu et al, 2016). These data highlight the necessity to elucidate the mechanisms underlying Aβ clearance by microglia, thereby attenuating AD progression.…”

Section: Introductionmentioning

confidence: 99%

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Adiponectin Regulates the Polarization and Function of Microglia via PPAR-γ Signaling Under Amyloid β Toxicity

Song

Choi

Kim

2017

Front. Cell. Neurosci.

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Alzheimer’s disease (AD), characterized by the abnormal accumulation of amyloid beta (Aβ), is gradually increasing globally. Given that AD is considered a neuroinflammatory disease, recent studies have focused on the cellular mechanisms in brain inflammatory conditions that underlie AD neuropathology. Microglia are macrophage cells in the central nervous system (CNS) that are activated in response to Aβ condition. The function of microglia contributes to the neuroinflammation in AD brain, suggesting that microglia regulate the production of inflammatory mediators and contribute to the regeneration of damaged tissues. Adiponectin, an adipokine derived from adipose tissue, has been known to regulate inflammation and control macrophages during oxidative stress conditions. In present study, we investigated whether adiponectin influences the polarization and function of microglia under Aβ toxicity by examining alterations of BV2 microglia function and polarization by Acrp30 (a globular form of adiponectin) treatment using reverse transcription PCR, western blotting and immunofluorescence staining. Acrp30 promoted the induction of the M2 phenotype, and regulated the inflammatory responses through peroxisome proliferator-activated receptor (PPAR)-γ signaling under Aβ toxicity. In addition, Acrp30 boosted the capacity of Aβ scavenging in microglia. Taken together, we suggest that adiponectin may control the function of microglia by promoting anti-inflammatory responses through PPAR- γ signaling. Hence, we conclude that adiponectin may act as a critical controller of microglia function in the AD brain.

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“…However, no clinical effects of anti-inflammatory treatment were observed in clinical trials [42,43,44]. According to the recent knowledge on microglia polarization, promoting M2-microglia phenotype may be a promising target, as shown by studies on preclinical models of stroke [45], TBI [46], AD [47], PD [48], ALS [49], and multiple sclerosis (MS) [50]. Nonetheless, targeting neuroinflammation in these diseases is even more complex and a regimen of anti-inflammatory treatments is also crucial.…”

Section: Involvement Of Activated Microglia In Brain Disordersmentioning

confidence: 99%

Molecular Targets for PET Imaging of Activated Microglia: The Current Situation and Future Expectations

Tronel

Largeau

Ribeiro

et al. 2017

IJMS

111

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Microglia, as cellular mediators of neuroinflammation, are implicated in the pathogenesis of a wide range of neurodegenerative diseases. Positron emission tomography (PET) imaging of microglia has matured over the last 20 years, through the development of radiopharmaceuticals targeting several molecular biomarkers of microglial activation and, among these, mainly the translocator protein-18 kDa (TSPO). Nevertheless, current limitations of TSPO as a PET microglial biomarker exist, such as low brain density, even in a neurodegenerative setting, expression by other cells than the microglia (astrocytes, peripheral macrophages in the case of blood brain barrier breakdown), genetic polymorphism, inducing a variation for most of TSPO PET radiopharmaceuticals’ binding affinity, or similar expression in activated microglia regardless of its polarization (pro- or anti-inflammatory state), and these limitations narrow its potential interest. We overview alternative molecular targets, for which dedicated radiopharmaceuticals have been proposed, including receptors (purinergic receptors P2X7, cannabinoid receptors, α7 and α4β2 nicotinic acetylcholine receptors, adenosine 2A receptor, folate receptor β) and enzymes (cyclooxygenase, nitric oxide synthase, matrix metalloproteinase, β-glucuronidase, and enzymes of the kynurenine pathway), with a particular focus on their respective contribution for the understanding of microglial involvement in neurodegenerative diseases. We discuss opportunities for these potential molecular targets for PET imaging regarding their selectivity for microglia expression and polarization, in relation to the mechanisms by which microglia actively participate in both toxic and neuroprotective actions in brain diseases, and then take into account current clinicians’ expectations.

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M2 Macrophage Transplantation Ameliorates Cognitive Dysfunction in Amyloid-β-Treated Rats Through Regulation of Microglial Polarization

Cited by 73 publications

References 57 publications

Low-level laser facilitates alternatively activated macrophage/microglia polarization and promotes functional recovery after crush spinal cord injury in rats

Low-level laser facilitates alternatively activated macrophage/microglia polarization and promotes functional recovery after crush spinal cord injury in rats

Adiponectin Regulates the Polarization and Function of Microglia via PPAR-γ Signaling Under Amyloid β Toxicity

Molecular Targets for PET Imaging of Activated Microglia: The Current Situation and Future Expectations

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