Attenuation of zinc-enhanced inflammatory M1 phenotype of microglia by peridinin protects against short-term spatial-memory impairment following cerebral ischemia in mice

Ueba, Yusuke; Aratake, Takaaki; Onodera, Kazunari; Higashi, Youichirou; Hamada, Takeomi; Shimizu, Takahiro; Shimizu, Shogo; Yawata, Toshio; Nakamura, Rina; Akizawa, Toshifumi; Ueba, Tetsuya; Saito, Motoaki

doi:10.1016/j.bbrc.2018.11.067

Cited by 13 publications

(15 citation statements)

References 23 publications

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“…After ONI, Zn 2+ accumulates in presynaptic boutons of amacrine cells from which it is exocytosed, contributing to RGC death and repression of regeneration after ONI [ 71 ]. In cell culture, the elevation of extracellular Zn 2+ exacerbates microglial activation to a pro-inflammatory M1 state, resulting in increased nitric oxide (NO) production and altered cytokine expression [ 72 , 73 , 74 , 75 ]. In vivo, reducing extracellular Zn 2+ via intraocular Zn 2+ chelators or genetic knockout of the vesicular Zn 2+ transporter ZnT3 reduces microglial activation after ONI [ 63 , 71 ], suggesting that Zn 2+ elevation in the retina may be one factor contributing to the microglial response after ONI.…”

Section: Role Of Microglia In Rgc Survival and Axon Regenerationmentioning

confidence: 99%

Retinal Ganglion Cell Survival and Axon Regeneration after Optic Nerve Injury: Role of Inflammation and Other Factors

Wong

Benowitz

2022

IJMS

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The optic nerve, like most pathways in the mature central nervous system, cannot regenerate if injured, and within days, retinal ganglion cells (RGCs), the neurons that extend axons through the optic nerve, begin to die. Thus, there are few clinical options to improve vision after traumatic or ischemic optic nerve injury or in neurodegenerative diseases such as glaucoma, dominant optic neuropathy, or optic pathway gliomas. Research over the past two decades has identified several strategies to enable RGCs to regenerate axons the entire length of the optic nerve, in some cases leading to modest reinnervation of di- and mesencephalic visual relay centers. This review primarily focuses on the role of the innate immune system in improving RGC survival and axon regeneration, and its synergy with manipulations of signal transduction pathways, transcription factors, and cell-extrinsic suppressors of axon growth. Research in this field provides hope that clinically effective strategies to improve vision in patients with currently untreatable losses could become a reality in 5–10 years.

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Section: Role Of Microglia In Rgc Survival and Axon Regenerationmentioning

confidence: 99%

Retinal Ganglion Cell Survival and Axon Regeneration after Optic Nerve Injury: Role of Inflammation and Other Factors

Wong

Benowitz

2022

IJMS

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“…6b). These results indicate that both GSGFK and GSGNR can resolve the aggregated Aβ 25-35. Animal experiments Y-maze test was performed at 11, 27, and 39 d after injection to evaluate the inhibitory effects of GSGFK on aggregates by measuring the spontaneous alternation rate [22]. The alternation rate of the Aβ25-35injected group induced signi cant short-term memory de cits as compared with that of the salineinjected group on all days (Day 11: p = 0.017, Day 27: p = 0.008, Day 39: p = 0.022).…”

Section: Resolving Effects On Aggregated Aβ 25-35mentioning

confidence: 99%

“…Mice were placed at the end of one arm and allowed to explore freely during a 10-min session while the series of arm entries was recorded. Alternation was said to occur if a mouse entered an arm distinct from the two entered previously [22]. The percentage of relative alternation was calculated as [number of alternations/(number of total arm entries-…”

Section: Spontaneous Alternation In Y-maze Testmentioning

confidence: 99%

Five-mer peptides, GSGFK and GSGNR suppress the aggregation of Aβ25-35 and resolve its aggregate form

Nakamura¹,

Konishi

Higashi³

et al. 2022

Preprint

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Background The development of drugs for Alzheimer’s disease (AD), which is related to the misfolding and aggregation of Amyloid-β (Aβ), is high in demand due to the growing number of AD patients. In this study, we screened 22 kinds of 5-mer synthetic peptides derived from the Box A region of Tob1 protein to find a peptide effective against Aβ aggregation. Methods A Thioflavin T (ThT) assay was performed to evaluate aggregation and screening aggregation inhibitor. Six weeks male ICR mice were administered of saline, 9 nmol Aβ25–35, or a mixture of 9 nmol Aβ25–35 and 9 nmol GSGFK in the right lateral ventricle. The short-term spatial memory assessed using Y-maze. The BV-2 cells were harvested into 24-well plates (4 × 104 cells/well) and incubated for 48 h and then, the cells were treated with 0.01, 0.05, 0.1, 0.2, or 0.5 mM of GSGFK. After incubation for 24 h, bead uptake was evaluated using a laser confocal microscope and Cytation 5. Results We found two kinds of peptides, GSGNR and GSGFK, were not only suppressed aggregation of Aβ25–35 but also resolved the aggregated Aβ25–35. Results obtained from the Y-maze test on an Aβ25-35-induced AD mouse model indicated that GSGFK prevents the deficits in short-term memory induced by Aβ25–35. The effect of GSGFK on phagocytosis in microglia cells (BV-2 cells) proved that GSGFK activates the phagocytic ability of microglia. Conclusions In conclusion, 5-mer peptides prevent short-term memory deficit in Aβ25–35 induced AD mouse model by reducing the aggregated Aβ25–35. They may also upregulate the phagocytic ability of microglia, which makes 5-mer peptides suitable candidates as therapeutic drugs against AD.

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“…Moreover, lithium reduced the number of OX6-positive cells microglia in the peri-hematomal zone as well as decreased the expression of the pro-inflammatory mediator COX2 during the early brain injury phase ( Kang et al, 2012 ). M1-type microglia promote the inflammatory response by releasing pro-inflammatory mediators, such as TNFα, IL1β, and IL6, exacerbating tissue damage ( Ueba et al, 2018 ), whereas M2-type microglia exert protective effects by promoting the release of anti-inflammatory mediators and trophic factors, and contribute to tissue repair ( Yang et al, 2018 ). Increasing the brain levels of Wnt1 via the delivery of rhWnt1 alleviated early brain injury associated to SAH in rats, which was accompanied by increased expression of β-catenin ( Wang Y. et al, 2019 ).…”

Section: The Wnt Pathway In Hemorrhagic Strokementioning

confidence: 99%

Wnt Pathway: An Emerging Player in Vascular and Traumatic Mediated Brain Injuries

2020

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The Wnt pathway, which comprises the canonical and non-canonical pathways, is an evolutionarily conserved mechanism that regulates crucial biological aspects throughout the development and adulthood. Emergence and patterning of the nervous and vascular systems are intimately coordinated, a process in which Wnt pathway plays particularly important roles. In the brain, Wnt ligands activate a cellspecific surface receptor complex to induce intracellular signaling cascades regulating neurogenesis, synaptogenesis, neuronal plasticity, synaptic plasticity, angiogenesis, vascular stabilization, and inflammation. The Wnt pathway is tightly regulated in the adult brain to maintain neurovascular functions. Historically, research in neuroscience has emphasized essentially on investigating the pathway in neurodegenerative disorders. Nonetheless, emerging findings have demonstrated that the pathway is deregulated in vascular-and traumatic-mediated brain injuries. These findings are suggesting that the pathway constitutes a promising target for the development of novel therapeutic protective and restorative interventions. Yet, targeting a complex multifunctional signal transduction pathway remains a major challenge. The review aims to summarize the current knowledge regarding the implication of Wnt pathway in the pathobiology of ischemic and hemorrhagic stroke, as well as traumatic brain injury (TBI). Furthermore, the review will present the strategies used so far to manipulate the pathway for therapeutic purposes as to highlight potential future directions.

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Attenuation of zinc-enhanced inflammatory M1 phenotype of microglia by peridinin protects against short-term spatial-memory impairment following cerebral ischemia in mice

Cited by 13 publications

References 23 publications

Retinal Ganglion Cell Survival and Axon Regeneration after Optic Nerve Injury: Role of Inflammation and Other Factors

Retinal Ganglion Cell Survival and Axon Regeneration after Optic Nerve Injury: Role of Inflammation and Other Factors

Five-mer peptides, GSGFK and GSGNR suppress the aggregation of Aβ25-35 and resolve its aggregate form

Wnt Pathway: An Emerging Player in Vascular and Traumatic Mediated Brain Injuries

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