| Reduced expression of APLP2 in spinal GABAergic inhibitory neurons contributed to nerve injury-induced microglial activation and pain sensitization | |
| Li, Yu-Zhe1; Zhu, Yue-Bin1; Ge, An-Na1; Gao, Min1; Wang, Kang-Li1; Zeng, Xiang-Ru1; Li, Jing1; Li, Yuan1; Xu, Jia-Yu1; Bai, Hu -Hu2,3; Wu, Shu-Jin1,4 | |
| 2023-02-15 | |
| Source Publication | NEUROPHARMACOLOGY
 |
| ISSN | 0028-3908 |
| Volume | 224 |
| Abstract | The amyloid precursor protein (APP) is critical for the pathogenesis of Alzheimer's disease (AD). The AD patients usually have lower pain sensitivity in addition to cognitive impairments. However, considerably less is known as yet about the role of APP and its two mammalian homologues, amyloid precursor-like protein 1 and 2 (APLP1, APLP2), in spinal processing of nociceptive information. Here we found that all APP family members were present in spinal cord dorsal horn of adult male C57BL/6J mice. Peripheral nerve injury specifically reduced the expression of spinal APLP2 that correlated with neuropathic mechanical allodynia. The loss of APLP2 was confined to inhibitory GABAergic interneurons. Targeted knockdown of APLP2 in GABAergic interneurons of GAD2-Cre mice evoked pain hypersensitivity by means of microglia activation. Our data showed that GABAergic terminals expressed APLP2, a putative cell adhesion protein that interacted with microglia-specific integrin molecule CD11b. Knocking down APLP2 in GAD2-positive neurons to disrupt the trans-cellular interaction led to microglia-dependent pain sensitization. Our data thus revealed an important role of APLP2 for GABAergic in-terneurons to control microglial activity and pain sensitivity. |
| Keyword | Amyloid precursor-like protein 2 Peripheral nerve injury Allodynia Hyperalgesia Microglia |
| Publisher | PERGAMON-ELSEVIER SCIENCE LTD |
| DOI | 10.1016/j.neuropharm.2022.109334 |
| Indexed By | SCIE |
| Language | 英语 |
| WOS Research Area | Neurosciences & Neurology ; Pharmacology & Pharmacy |
| WOS Subject | Neurosciences ; Pharmacology & Pharmacy |
| WOS ID | WOS:000895790100001 |
| Original Document Type | Article |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | https://ir.lzu.edu.cn/handle/262010/492414 |
| Collection | 兰州大学 |
| Affiliation | 1.Lanzhou Univ, Sch Pharm, Dept Mol Pharmacol, Lanzhou 730000, Gansu, Peoples R China; 2.Lanzhou Univ, Sch Life Sci, Lanzhou 730000, Gansu, Peoples R China; 3.Lanzhou Univ, Sch Life Sci, 222 South Tianshui Rd, Lanzhou 730000, Gansu, Peoples R China; 4.Lanzhou Univ, Sch Pharm, Dept Mol Pharmacol, 222 South Tianshui Rd, Lanzhou 730000, Gansu, Peoples R China |
| First Author Affilication | School of Pharmacy |
| Recommended Citation GB/T 7714 | Li, Yu-Zhe,Zhu, Yue-Bin,Ge, An-Na,et al. Reduced expression of APLP2 in spinal GABAergic inhibitory neurons contributed to nerve injury-induced microglial activation and pain sensitization[J]. NEUROPHARMACOLOGY,2023,224. |
| APA | Li, Yu-Zhe.,Zhu, Yue-Bin.,Ge, An-Na.,Gao, Min.,Wang, Kang-Li.,...&Wu, Shu-Jin.(2023).Reduced expression of APLP2 in spinal GABAergic inhibitory neurons contributed to nerve injury-induced microglial activation and pain sensitization.NEUROPHARMACOLOGY,224. |
| MLA | Li, Yu-Zhe,et al."Reduced expression of APLP2 in spinal GABAergic inhibitory neurons contributed to nerve injury-induced microglial activation and pain sensitization".NEUROPHARMACOLOGY 224(2023). |
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