Xiaolong Wang1, Biwen Peng2, Chang Xu1, Zhengyan Gao1, Yuanfei Cao1, Zhao Liu1, Tongzu Liu3,4. 1. Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan University, 169 Donghu Rd, Wuhan, 430071, China. 2. Department of Physiology, School of Basic Medical Sciences, Wuhan University, 185 Donghu Rd, Wuhan, 430071, China. 3. Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan University, 169 Donghu Rd, Wuhan, 430071, China. wangxl890204@163.com. 4. Department of Physiology, School of Basic Medical Sciences, Wuhan University, 185 Donghu Rd, Wuhan, 430071, China. wangxl890204@163.com.
Abstract
OBJECTIVES: Long-term ketamine abuse can affect the urinary system, resulting in lower urinary tract symptoms (LUTS), but the pathogenesis of this is still unknown. Previous studies have demonstrated that ketamine can change the expression of the brain-derived neurotrophic factor (BDNF) in the serum of ketamine abuse patients. The aim of the present study is to explore the mechanism of the ketamine-mediated BDNF signaling pathway in the bladder of rats on chronic ketamine treatment. METHODS: Rats were randomly assigned to a control (normal saline) or ketamine (30 mg/kg) group, with five rats in each group. The experimental group was given ketamine via intraperitoneal injection daily, while the control group was treated with saline. After 12 weeks of treatment, bladders were excised and samples from the control and ketamine group were examined with transmission electron microscopy (TEM). Phosphoprotein and non-phosphoprotein purification, histopathology, immunohistochemistry, and western blot were carried out in all groups. RESULTS: Histological study showed hyperplastic epithelium and inflammatory cell infiltration in ketamine-treated rat bladders. TEM showed that chronic ketamine treatment results in structural damage to organelles. Immunohistochemical staining and western blot showed that the expression of BDNF was significantly lower in the ketamine group. However, the expression of phosphorylated extracellular signal-regulated kinases ½ (ERK1/2) in the ketamine group was higher, whereas the total ERK1/2 was similar to the control group. CONCLUSIONS: Long-term ketamine abuse reduces expression of BDNF, while inducing phosphorylation of ERK1/2 in the bladder wall. This may play an important role in the pathogenesis of ketamine-associated LUTS.
OBJECTIVES: Long-term ketamine abuse can affect the urinary system, resulting in lower urinary tract symptoms (LUTS), but the pathogenesis of this is still unknown. Previous studies have demonstrated that ketamine can change the expression of the brain-derived neurotrophic factor (BDNF) in the serum of ketamine abuse patients. The aim of the present study is to explore the mechanism of the ketamine-mediated BDNF signaling pathway in the bladder of rats on chronic ketamine treatment. METHODS:Rats were randomly assigned to a control (normal saline) or ketamine (30 mg/kg) group, with five rats in each group. The experimental group was given ketamine via intraperitoneal injection daily, while the control group was treated with saline. After 12 weeks of treatment, bladders were excised and samples from the control and ketamine group were examined with transmission electron microscopy (TEM). Phosphoprotein and non-phosphoprotein purification, histopathology, immunohistochemistry, and western blot were carried out in all groups. RESULTS: Histological study showed hyperplastic epithelium and inflammatory cell infiltration in ketamine-treated rat bladders. TEM showed that chronic ketamine treatment results in structural damage to organelles. Immunohistochemical staining and western blot showed that the expression of BDNF was significantly lower in the ketamine group. However, the expression of phosphorylated extracellular signal-regulated kinases ½ (ERK1/2) in the ketamine group was higher, whereas the total ERK1/2 was similar to the control group. CONCLUSIONS: Long-term ketamine abuse reduces expression of BDNF, while inducing phosphorylation of ERK1/2 in the bladder wall. This may play an important role in the pathogenesis of ketamine-associated LUTS.