Role of Glu-mGluR2/3-ERK signaling pathway in apoptosis of neurons in the prefrontal cortex of diabetic rats with depression
(2.Central Laboratory, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan Province, China 410007)
【Abstract】Aim To investigate the key role of Glu-mGluR2/3-ERK signaling pathway in the apoptosis of prefrontal cortex neurons in diabetic rats with depression (DD). Methods Animal experiments were divided into two parts. The first part was divided into four groups: control, diabetes, depression and DD group. The second part was divided into three groups: control, DD, mGluR2/3 blocker + DD group (LY341495 group). Hormonal and Morris water maze tests were used to evaluate the depression-like behavior of rats. HE staining was used to observe the pathological damage in the prefrontal cortex. HPLC was applied to determine glutamate (Glu) content, and immunohistochemistry was employed to assess the positive expression of mGluR2/3, ERK, and caspase-3. Results Compared with control group, the depression-like behavior of the rats in DD model group was obvious. The prefrontal cortex neurons had pathological lesions such as swelling of the cell body, nuclear condensation, disordered arrangement, and reduced number, and the positive expression of caspase-3 was increased significantly. Meanwhile, Glu content was increased abnormally, its receptor mGluR2/3 expression was increased, and the downstream molecules ERK expression was decreased, indicating that neuronal apoptosis might be related to Glu-mGluR2/3-ERK pathway. Further study revealed that after the administration of mGluR2/3 blocker LY341495, the expression levels of mGluR2/3, ERK and caspase-3 in the prefrontal cortex of rats in DD group were reversed, and the pathological damage was alleviated to some extent. Conclusion The Glu-mGluR2/3-ERK signaling pathway is involved in the apoptosis of prefrontal cortex neurons in DD rats.
【Keywords】 diabetic depression; prefrontal cortex; glutamate; neuronal apoptosis; mGluR2/3; ERK;
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