Triggering receptor expressed on myeloid cells 2 (TREM2) dependent microglial activation promotes cisplatin-induced peripheral neuropathy in mice

Hu, Lang-Yue; Zhou, Yang; Cui, Weihong; Hu, Xue-Ming; Du, Lixia; Mi, Wen-Li; Chu, Yu‐Xia; Wu, Gen-Cheng; Wang, Yanqing; Mao-Ying, Qi-Liang

doi:10.1016/j.bbi.2017.10.011

Cited by 69 publications

(66 citation statements)

References 61 publications

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“…Notably, the administration of resveratrol ameliorated mechanical allodynia and decreased the level of in ammatory cytokines in the SDH while inhibiting the microglia activation. Similar inhibitory effects of resveratrol on in ammation were observed in the nerve injury model lacking DAP12 or TREM2, and AD model [24,33,34]. These results suggested that microglia activation was inhibited by resveratrol in the pathology of NeuP.…”

Section: Discussionsupporting

confidence: 68%

Resveratrol Mediates Mechanical Allodynia Through Modulating Inflammatory Response via the TREM2-autophagy Axis in SNI Rat Model

Wang

Shi

Huang

et al. 2020

Preprint

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Background Neuropathic pain (NeuP) is a chronic and challenging clinical problem, with little effective treatment. Resveratrol has shown neuroprotection by inhibiting inflammatory response in NeuP. Recently, the triggering receptor expressed on myeloid cells 2 (TREM2) expressed by microglia was identified as a critical factor of inflammation in nervous system diseases. In this study, we explored whether resveratrol could ameliorate neuroinflammation and produce anti-mechanical allodynia effects via regulating TREM2 in spared nerve injury rats, as well as investigated the underlying mechanisms. Methods A spared nerve injury (SNI) rat model was performed to investigate whether resveratrol could exert anti-mechanism allodynia effects via inhibiting neuroinflammation. To evaluate the role of TREM2 in anti-neuroinflammatory function of resveratrol, Lentivirus coding TREM2 was intrathecal injected into SNI rats to activate TREM2 and the pain behavior was detected by the Von Frey test. Furthermore, 3-Methyladenine (3-MA, an autophagy inhibitor) was performed to analyze the molecular mechanisms of resveratrol-mediated anti-neuroinflammation using Western blot, qPCR, immunofluorescence. Results The TREM2 expression and number of the microglial cell was significantly increased in the ipsilateral spinal dorsal horn after SNI. We found that intrathecal administration of resveratrol (300ug/day) alleviated mechanical allodynia; obviously enhanced autophagy; and markedly reduced the levels of interleukin-1β, interleukin-6, and tumor necrosis factor-α in the ipsilateral spinal dorsal horn after SNI. Moreover, the number of Iba-1+ microglial cells and TREM2 expression were downregulated after resveratrol treatment. Intrathecal administration of lentivirus coding TREM2 and/or 3-methyladenine in those rats induced deficiencies in resveratrol-mediated anti-inflammation, leading to mechanical allodynia that could be rescued via administration of Res. Furthermore, 3-MA treatment contributed to TREM2-mediated mechanical allodynia. Conclusions Taken together, these data reveal that resveratrol relieves neuropathic pain through suppressing microglia-mediated neuroinflammation via regulating the TREM2-autophagy axis in SNI rats.

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Section: Discussionsupporting

confidence: 68%

Resveratrol Mediates Mechanical Allodynia Through Modulating Inflammatory Response via the TREM2-autophagy Axis in SNI Rat Model

Wang

Shi

Huang

et al. 2020

Preprint

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“…Furthermore, minocycline administration reduces central levels of pro-inflammatory cytokines and microglial activation, attenuating depressive-like behavior in tumor-bearing mice ( 55 ). Similarly, minocycline administration or functional blockade of a receptor expressed on myeloid cells attenuates cisplatin-induced CIPN ( 227 ) by suppressing the microglial pro-inflammatory response.…”

Section: Anti-inflammatory Interventions (Pharmacological and Non-phamentioning

confidence: 99%

Neuroimmunology of Behavioral Comorbidities Associated With Cancer and Cancer Treatments

Santos

Pyter

2018

Front. Immunol.

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Behavioral comorbidities (depression, anxiety, fatigue, cognitive disturbances, and neuropathic pain) are prevalent in cancer patients and survivors. These mental and neurological health issues reduce quality-of-life, which is a significant societal concern given the increasing rates of long-term survival after various cancers. Hypothesized causes of behavioral comorbidities with cancer include tumor biology, stress associated with the cancer experience, and cancer treatments. A relatively recent leading mechanism by which these causes contribute to changes in neurobiology that underlie behavior is inflammation. Indeed, both basic and clinical research indicates that peripheral inflammation leads to central inflammation and behavioral changes in other illness contexts. Given the limitations of assessing neuroimmunology in clinical populations, this review primarily synthesizes evidence of neuroimmune and neuroinflammatory changes due to two components of cancer (tumor biology and cancer treatments) that are associated with altered affective-like or cognitive behaviors in rodents. Specifically, alterations in microglia, neuroinflammation, and immune trafficking to the brain are compiled in models of tumors, chemotherapy, and/or radiation. Evidence-based neuronal mechanisms by which these neuroimmune changes may lead to changes in behavior are proposed. Finally, converging evidence in clinical cancer populations is discussed.

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“…Antineoplastic treatments have been shown to be cytotoxic to Schwann cells through the formation of inclusion bodies and vacuoles, whereas proliferation of Langerhans cells in the skin is a by-product of inflammation and leads to the loss of intraepidermal nerve fibers. Similarly, inflammatory mechanisms can induce the accumulation of macrophages in dorsal root ganglia (DRG), leading to injury and peripheral neuropathy (7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

SIRT2 protects peripheral neurons from cisplatin-induced injury by enhancing nucleotide excision repair

Zhang¹,

Du²,

Acklin³

et al. 2020

Journal of Clinical Investigation

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Triggering receptor expressed on myeloid cells 2 (TREM2) dependent microglial activation promotes cisplatin-induced peripheral neuropathy in mice

Cited by 69 publications

References 61 publications

Resveratrol Mediates Mechanical Allodynia Through Modulating Inflammatory Response via the TREM2-autophagy Axis in SNI Rat Model

Resveratrol Mediates Mechanical Allodynia Through Modulating Inflammatory Response via the TREM2-autophagy Axis in SNI Rat Model

Neuroimmunology of Behavioral Comorbidities Associated With Cancer and Cancer Treatments

SIRT2 protects peripheral neurons from cisplatin-induced injury by enhancing nucleotide excision repair

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