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Le, Yue; Chen, Xin; Wang, Long; He, Wan-you; He, Jian; Xiong, Qing-ming; Wang, Yun-hua; Zhang, Lei; Zheng, Xue-qin; Wang, Han-bing
Brain research bulletin, October 2021, 2021-10-00, 20211001, Letnik: 175Journal Article
•IGF-1 decreases in the spinal cord after chemotherapy.•IGF-1 is mainly expressed in astrocytes while IGF-1R exclusively on neurons in the spinal cord.•Chemotherapy up-regulates neuroinflammation (IL-17A & TNF-α) and nociceptive neuropeptides.•Treatment with rIGF-1 rescues CIPN and attenuates the spinal inflammatory response. Chemotherapy-induced peripheral neuropathy (CIPN) is a common and intractable complication in chemotherapy-receiving patients. Insulin-like growth factor-1 (IGF-1) is a popular neurotrophin with various functions, such as maintaining neuronal survival and synaptic functioning in the central nervous system. Therefore, we hypothesized that the IGF-1 signaling pathway could be a candidate target for treating CIPN. We established the CIPN model by injecting mice intraperitoneally with oxaliplatin and assessed IGF-1 protein expression, its receptor IGF1R, phospho-IGF1R (p-IGF1R), interleukin-17A (IL-17A), tumor necrosis factor-α (TNF-α), and calcitonin gene-related peptide (CGRP) in the lumbar spinal cord with Western blot and immunofluorescence. To examine the effect of IGF-1 signaling on CIPN, we injected mice intrathecally or intraperitoneally with mouse recombinant IGF-1 (rIGF-1). IGF-1 protein expression decreased significantly in the spinal cord on D3 and D10 (the 3rd and 10th days after beginning oxaliplatin chemotherapy) and was co-localized with astrocytes primarily in the lumbar spinal cord, whereas IGF1R was predominantly expressed on neurons. Both intrathecally- and intraperitoneally-administered rIGF-1 relieved the chemotherapy-induced pain-like behavior and reduced IL-17A, TNF-α, and CGRP protein expressions in the spinal cord. Our results indicate a vital role for IGF-1 signaling in CIPN. Targeting IGF-1 signaling could be a potent therapeutic strategy for treating CIPN in clinical settings.
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Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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