Astrocytic NDRG2 is involved in glucocorticoid-mediated diabetic mechanical allodynia
Zhong-Fu Zuo1, Yong-Hui Liao2, Tan Ding2
1Department of Anatomy, Histology and Embryology & K.K. Leung Brain Research Centre, Preclinical School of Medicine, The Fourth Military Medical University, Xi'an 710032, PR China; Department of Anatomy, Histology and Embryology, Liaoning Medical University, No. 3-40 Songpo Road, Jinzhou, Liaoning 121000, PR China.
Aims:
The present study aims to test whether astrocytes contribute to glucocorticoid-mediated diabetic mechanical allodynia.
Methods:
Streptozotocin (STZ)-induced diabetic rats were used in our study. The intrathecal operation was performed 21 days after the onset of diabetes. Diabetic mechanical allodynia was present 28 d after the onset of diabetes, and the mechanical threshold was tested using von Frey filaments. Immunohistochemistry, including immunofluorescent histochemical staining, was performed to observe the morphology of the spinal dorsal horn (SDH). Western blot analysis was employed as a semi-quantitative assay of the expression levels of GFAP and NDRG2 associated with diabetic mechanical allodynia.
Results:
Diabetic rats displayed mechanical allodynia and activated astrocytes in the SDH 28 days after the onset of diabetes. This allodynia was attenuated by intrathecal administration of the astrocyte-specific inhibitor l-α-aminoadipate. In parallel, intrathecal injection of RU486, a glucocorticoid receptor antagonist, inhibited the activation of astrocytes in the SDH, alleviating the diabetes-induced mechanical allodynia. Furthermore, we found that dorsal horn astrocytes express abundant N-myc downstream-regulated gene 2 (NDRG2), which contributes to astrocyte reactivity. NDRG2 was over-expressed in activated astrocytes in diabetic rats with mechanical allodynia. Intrathecal injection of RU486 prevented the over-expression of NDRG2, which reversed the astrocyte reactivity and diabetic tactile allodynia.
Conclusions:
These results suggest that glucocorticoid-mediated over-expression of NDRG2 may contribute to the activation of dorsal horn astrocytes, which play a crucial role in diabetic mechanical allodynia. Thus, inhibiting glucocorticoid receptors and/or astrocyte reactivity in the SDH may be a therapeutic strategy for treating diabetic tactile allodynia.
