Protective effects of dihydromyricetin on primary hippocampal astrocytes from cytotoxicity induced by comorbid diabetic
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ORIGINAL ARTICLE
Protective effects of dihydromyricetin on primary hippocampal astrocytes from cytotoxicity induced by comorbid diabetic neuropathic pain and depression Huixiang Ge 1 & Mengyun Sun 1 & Xingyu Wei 2 & Mingming Zhang 1 & Hongcheng Tu 3 & Yuanzhen Hao 4 & Ruxin Chen 2 & Miao Ye 2 & Yun Gao 1,5 Received: 18 August 2020 / Accepted: 26 October 2020 # Springer Nature B.V. 2020
Abstract Activated astrocytes play a key role in diabetic neuropathic pain and depression. We aimed to assess the protective effects of dihydromyricetin (DHM) on primary hippocampal astrocytes cultured with high glucose (HG), substance P (SP), and corticosterone (CORT). Culturing with HG + SP + CORT resulted in damage to primary hippocampal astrocytes, which simulates the clinical damage caused by comorbidity of diabetic neuropathic pain and depression. Western blot, qPCR, and immunofluorescence analyses revealed that HG + SP + CORT increased P2X7 receptor expression in primary hippocampal astrocytes, which was reversed by DHM treatment. Further, HG + SP + CORT elevated TNF-α, IL-1β, free Ca2+, and ERK1/2 phosphorylation levels, which was inhibited by DHM or P2X7 shRNA treatment. Moreover, DHM significantly reduced the P2X7 agonistactivated currents in HEK293 cells transfected with the P2X7 receptor. These findings suggest that DHM can protect primary hippocampal astrocytes cultured with HG + SP + CORT from P2X7 receptor-mediated damage. Culturing cells with HG + SP + CORT might be a viable cell model for cellular injury exploration of diabetic comorbid pain and depression. Keywords Dihydromyricetin . Diabetic neuropathic pain . Depression . Hippocampal astrocyte . P2X7 receptor
Introduction Diabetes is the most common chronic disease and is characterized by intractable hyperglycemia. In the twenty-first century, it has been reported to present a heavy public health and economic burden worldwide [1]. Diabetic neuropathic pain (DNP) is a
Huixiang Ge, Mengyun Sun, and Xingyu Wei Joint first authors * Yun Gao [email protected] 1
Department of Physiology, Basic Medical College of Nanchang University, 461 Bayi Road, Nanchang, Jiangxi, China
2
Medical College of Grade 2017, Nanchang University, Nanchang, Jiangxi, People’s Republic of China
3
Medical College of Grade 2018, Nanchang University, Nanchang, Jiangxi, People’s Republic of China
4
Queen Mary College of Grade 2016, Nanchang University, Nanchang, Jiangxi, People’s Republic of China
5
Jiangxi Provincial Key Laboratory of Autonomic Nervous Function and Disease, Nanchang, Jiangxi, People’s Republic of China
disabling complication in patients with diabetes that is extremely difficult to treat [2]. The main clinical manifestations of DNP are spontaneous pain, allodynia, and hyperalgesia [3]. Depression (DP) is one of the most common diseases in the world and has gradually become a major public health issue in China; it poses a heavy financial burden on patients [4]. Previous studies have reported a bidirectional causality between diabetes and depression [5, 6]. Patients wit
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