Department of Molecular Medicine, USF Health Byrd Institute, University of South Florida, Tampa, FL 33613, USA.
Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, FL 33620, USA.
Cells. 2020 Jan 14;9(1):210. doi: 10.3390/cells9010210.
Tau dysfunction is common in several neurodegenerative diseases including Alzheimer's disease (AD) and frontotemporal dementia (FTD). Affective symptoms have often been associated with aberrant tau pathology and are commonly comorbid in patients with tauopathies, indicating a connection between tau functioning and mechanisms of depression. The current study investigated depression-like behavior in mice, which contain a targeted deletion of the gene coding for tau. We show that 6-month mice are resistant to depressive behaviors, as evidenced by decreased immobility time in the forced swim and tail suspension tests, as well as increased escape behavior in a learned helplessness task. Since depression has also been linked to deficient adult neurogenesis, we measured neurogenesis in the hippocampal dentate gyrus and subventricular zone using 5-bromo-2-deoxyuridine (BrdU) labeling. We found that neurogenesis is increased in the dentate gyrus of 14-month-old brains compared to wild type, providing a potential mechanism for their behavioral phenotypes. In addition to the hippocampus, an upregulation of proteins involved in neurogenesis was observed in the frontal cortex and amygdala of the mice using proteomic mass spectrometry. All together, these findings suggest that tau may have a role in the depressive symptoms observed in many neurodegenerative diseases and identify tau as a potential molecular target for treating depression.
tau 功能障碍在包括阿尔茨海默病（AD）和额颞叶痴呆（FTD）在内的几种神经退行性疾病中很常见。情感症状通常与异常 tau 病理学有关，并且在 tau 病患者中经常合并存在，这表明 tau 功能与抑郁机制之间存在联系。本研究在携带 tau 基因靶向缺失的小鼠中研究了类似抑郁的行为。我们表明，6 个月大的 小鼠对抑郁行为具有抗性，这表现在强迫游泳和悬尾试验中不动时间减少，以及在习得性无助任务中逃避行为增加。由于抑郁也与成人神经发生不足有关，我们使用 5-溴-2-脱氧尿苷（BrdU）标记测量海马齿状回和侧脑室下区的神经发生。我们发现，与野生型相比，14 月龄 大脑的齿状回中的神经发生增加，为其行为表型提供了潜在的机制。除了海马体外，使用蛋白质组学质谱法还观察到 小鼠的前额叶皮层和杏仁核中参与神经发生的蛋白质上调。综上所述，这些发现表明 tau 可能在许多神经退行性疾病中观察到的抑郁症状中起作用，并将 tau 确定为治疗抑郁的潜在分子靶标。
