Enriched environment alleviates stress-induced dry-eye through the BDNF axis
Enriched environment alleviates stress-induced dry-eye through the BDNF axis
复制标题
DOI：
10.1038/s41598-019-39467-w
复制
发表时间：
2019-03-04
影响因子：
4.6
通讯作者：
Tsubota, Kazuo
中科院分区：
文献类型：
--
作者：
Sano, Kokoro;Kawashima, Motoko;Tsubota, Kazuo
干眼病（DED）患者数量不断增加，已成为一个紧迫的公共卫生问题。在DED患者中有精神障碍的合并症的报道。我们假设生理和心理压力源损害泪液分泌。为了研究应激负荷与泪液分泌减少之间的关系，我们建立了应激诱导的DED小鼠模型，这使我们能够解决其发病机制和恢复能力的潜在机制。强化环境（EE）是预防和缓解应激性泪液分泌减少的有效干预措施。由于应激负荷导致脑源性神经营养因子（BDNF）表达减少，而EE导致表达增加，因此我们重点研究了BDNF在泪液分泌中的作用。使用两只不同的Bdnf基因敲除小鼠，我们评估了Bdnf是否在健康和应激条件下调节泪液分泌的决定性因素。Bdnf敲除小鼠显示基底泪液分泌减少，EE对泪液分泌的应激耐受性下降。这些结果表明BDNF的表达与泪液分泌和DED的病理有关。
The number of patients with dry eye disease (DED) is increasing, and DED has become an urgent public health problem. A comorbidity of mental disorders has been reported in DED patients. We hypothesized that physical and psychological stressors impair tear secretion. To examine the relationship between stress loading and decreased tear secretion, we established a stress-induced DED mouse model, which permitted us to address the underlying mechanism of pathogenesis and resilience. Enriched environment (EE) was an effective intervention to prevent and alleviate stress-induced decreased tear secretion. Because stress loading resulted in decreased brain-derived neurotrophic factor (BDNF) expression while EE resulted in increased expression, we focused on the role of BDNF in tear secretion. Using two distinct Bdnf gene knockdown mice, we evaluated whether BDNF was a deterministic factor in regulating tear secretion in healthy and stressed conditions. Bdnf knockdown mice showed decreased basal tear secretion and loss of stress tolerance by EE for tear secretion. These results suggest that BDNF expression is related to tear secretion and to the pathology of DED.