Neuroprotection by dihydrotestosterone in LPS-induced neuroinflammation

Yang, Lei; Zhou, Renyuan; Tong, Y.Z.; Chen, Pengfei; Yu, Shaohua; Miao, Shuai; Liu, Xiaoqiang

doi:10.1016/j.nbd.2020.104814

Cited by 121 publications

(81 citation statements)

References 46 publications

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“…However, the modulatory roles of PTE in microglial activation and following injury have not been given enough attention. Neurodegenerative diseases have strong connections with microglial activation [50,51]. A recent study compared the protective effects of PTE and its structural analogues on neurodegenerative diseases.…”

Section: Oxidative Medicine and Cellular Longevitymentioning

confidence: 99%

Pterostilbene Attenuates Cocultured BV-2 Microglial Inflammation-Mediated SH-SY5Y Neuronal Oxidative Injury via SIRT-1 Signalling

Zhu

Tang

Liu

et al. 2020

Oxidative Medicine and Cellular Longevity

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Microglial inflammation plays an important part in the progression of multiple neurological diseases, including neurodegenerative diseases, stroke, depression, and traumatic encephalopathy. Here, we aimed to explore the role of pterostilbene (PTE) in the microglial inflammatory response and subsequent damage of cocultured neural cells and partially explain the underlying mechanisms. In the coculture system of lipopolysaccharide-activated BV-2 microglia and SH-SY5Y neuroblastoma, PTE (only given to BV-2) exhibited protection on SH-SY5Y cells, evidenced by improved SH-SY5Y morphology and viability and LDH release. It also attenuated SH-SY5Y apoptosis and oxidative stress, evidenced by TUNEL and DCFH-DA staining, as well as MDA, SOD, and GSH levels. Moreover, PTE upregulated SIRT-1 expression and suppressed acetylation of NF-κB p65 subunit in BV-2 microglia, thus decreasing the inflammatory factors, including TNF-α and IL-6. Furthermore, the effects above were reversed by SIRT-1 inhibitor EX527. These results suggest that PTE reduces the microglia-mediated inflammatory response and alleviates subsequent neuronal apoptosis and oxidative injury via increasing SIRT-1 expression and inhibiting the NF-κB signalling pathway.

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Section: Oxidative Medicine and Cellular Longevitymentioning

confidence: 99%

Pterostilbene Attenuates Cocultured BV-2 Microglial Inflammation-Mediated SH-SY5Y Neuronal Oxidative Injury via SIRT-1 Signalling

Zhu

Tang

Liu

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…Few studies have focused on the effects of androgens on neuroinflammation. Yang et al investigated the neuroprotective role of androgens (including testosterone and its metabolite dihydrotestosterone, DHT) in lipopolysaccharide (LPS)-induced neuroinflammation, neuronal damage, and behavioral dysfunction [18]. DHT potentially inhibits the LPS-induced release of proinflammatory factors in primary microglia by suppressing the TLR4-mediated NF-κB and p38 signaling pathways, thus protecting neurons from inflammatory damage induced by activated microglia.…”

Section: Degenerative Nerve Diseasesmentioning

confidence: 99%

“…The pathological hallmarks of Alzheimer's disease (AD) are the accumulation of extracellular plaques and intracellular neurofibrillary tangles that are composed of filaments of β-amyloid polymers and the neuronal microtubule-associated protein Tau, respectively. Elevated β-amyloid levels in an AD brain are speculated to induce microglial activation and the consequent release of proinflammatory cytokines induced by the p38 MAPK pathway, potentially contributing to AD pathogenesis together with other disorders including neuronal injury, trauma, ischemia, and the accumulation of oxidants associated with brain aging [16,18,224].…”

Section: Alzheimer's Diseasementioning

confidence: 99%

“…Moreover, the p38 MAPK activator, MKK6, is active in neurodegenerative diseases, indicating a potential contribution to Tau hyperphosphorylation in these diseases. Recent studies have reported that Tau is a suitable in vitro substrate for p38 isoforms p38δ and p38γ, and its phosphorylation by these two enzymes reduces its ability to promote microtubule assembly [18,[225][226][227][228]. Moreover, p38γ overexpression in neuroblastoma induces Tau phosphorylation, which is associated with a reduction in Tau that is associated with the cytoskeleton and an increase in soluble Tau.…”

Section: Alzheimer's Diseasementioning

confidence: 99%

“…Acupuncture is widely used to treat various diseases and exerts positive effects, including analgesia, at both local and systemic levels [3,[8][9][10][11][12]; it improves consciousness and cognition [13][14][15][16][17][18][19][20], and it induces therapeutic effects in several nervous system diseases [8,[13][14][15][16][17][18][19][20]. Advanced molecular and clinical studies have continually attempted to decipher the mechanisms underlying these effects of acupuncture [2,7,16,17,.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Effect of Acupuncture on the p38 Signaling Pathway in Several Nervous System Diseases: A Systematic Review

Wei

Hsieh

2020

IJMS

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Acupuncture is clinically used to treat various diseases and exerts positive local and systemic effects in several nervous system diseases. Advanced molecular and clinical studies have continually attempted to decipher the mechanisms underlying these effects of acupuncture. While a growing understanding of the pathophysiology underlying several nervous system diseases shows it to be related to inflammation and impair cell regeneration after ischemic events, the relationship between the therapeutic mechanism of acupuncture and the p38 MAPK signal pathway has yet to be elucidated. This review discusses the latest advancements in the identification of the effect of acupuncture on the p38 signaling pathway in several nervous system diseases. We electronically searched databases including PubMed, Embase, and the Cochrane Library from their inception to April 2020, using the following keywords alone or in various combinations: “acupuncture”, “p38 MAPK pathway”, “signaling”, “stress response”, “inflammation”, “immune”, “pain”, “analgesic”, “cerebral ischemic injury”, “epilepsy”, “Alzheimer’s disease”, “Parkinson’s disease”, “dementia”, “degenerative”, and “homeostasis”. Manual acupuncture and electroacupuncture confer positive therapeutic effects by regulating proinflammatory cytokines, ion channels, scaffold proteins, and transcription factors including TRPV1/4, Nav, BDNF, and NADMR1; consequently, p38 regulates various phenomena including cell communication, remodeling, regeneration, and gene expression. In this review article, we found the most common acupoints for the relief of nervous system disorders including GV20, GV14, ST36, ST37, and LI4. Acupuncture exhibits dual regulatory functions of activating or inhibiting different p38 MAPK pathways, contributing to an overall improvement of clinical symptoms and function in several nervous system diseases.

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In Situ Detection of Neuroinflammation Using Multicellular 3D Neurovascular‐Unit‐on‐a‐Chip

Choi,

Lee

2023

Adv Funct Materials

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The human neurovascular system is a complex network of blood vessels and brain cells that is essential to the proper functioning of the brain. Researchers have become increasingly interested in the system for developing drugs to treat neuroinflammation. Currently, creating neurovascular models begins with animal models, followed by testing on humans in clinical trials. However, the high number of medication failures that pass through animal testing indicates that animal models do not always reflect the outcome of human clinical trials. To overcome the challenges of the issues with animal models, a neurovascular‐unit‐on‐a‐chip system is developed to accurately replicate the in vivo human neurovascular microenvironment. By replicating the human neurovascular unit, a more accurate representation of human physiology can be achieved compared to animal models. The ability to detect proinflammatory cytokines in situ and monitor physiological changes can provide an invaluable tool for evaluating the efficacy and safety of drugs. Using nanosized graphene oxide for in situ detection of inflammatory responses is an innovative approach that can advance the field of neuroinflammation research. Overall, the developed neuroinflammation‐on‐a‐chip system has the potential to provide a more efficient and effective method for developing drugs for treating neurodegenerative diseases and other central nervous system diseases.

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Neuroprotection by dihydrotestosterone in LPS-induced neuroinflammation

Cited by 121 publications

References 46 publications

Pterostilbene Attenuates Cocultured BV-2 Microglial Inflammation-Mediated SH-SY5Y Neuronal Oxidative Injury via SIRT-1 Signalling

Pterostilbene Attenuates Cocultured BV-2 Microglial Inflammation-Mediated SH-SY5Y Neuronal Oxidative Injury via SIRT-1 Signalling

Effect of Acupuncture on the p38 Signaling Pathway in Several Nervous System Diseases: A Systematic Review

In Situ Detection of Neuroinflammation Using Multicellular 3D Neurovascular‐Unit‐on‐a‐Chip

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