Department of Psychology, University of Calgary, 2500 University Drive NW, Calgary, Alberta T2N 1N4, Canada; Hotchkiss Brain Institute, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta T2N 4N1, Canada.
Department of Psychology, University of Calgary, 2500 University Drive NW, Calgary, Alberta T2N 1N4, Canada; Hotchkiss Brain Institute, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta T2N 4N1, Canada; Alberta Children's Hospital Research Institute, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta T2N 4N1, Canada.
Neuroscience. 2020 Jan 15;425:90-100. doi: 10.1016/j.neuroscience.2019.11.009. Epub 2019 Nov 27.
In certain neurons, zinc ions are stored in synaptic vesicles by zinc transporter 3 (ZnT3). Vesicular zinc can then be released synaptically to modulate myriad targets. In vitro evidence indicates that these targets may include brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin receptor kinase B (TrkB). But the effects of vesicular zinc on BDNF and TrkB in the intact brain are unclear. Studies of mice that lack ZnT3 - and, as a result, vesicular zinc - have shown abnormalities in BDNF and TrkB levels, but results have been mixed and are therefore difficult to interpret. This might be caused by differences in the age or sex of mice tested. In the present study, we measured BDNF and TrkB levels in the hippocampus and neocortex, comparing wild type and ZnT3 knockout mice of both sexes at two ages (5 and 12 weeks). We also examined BDNF mRNA expression and protein levels at an intermediate age (8-10 weeks). We found that, regardless of age or sex, BDNF and TrkB protein levels did not differ between wild type and ZnT3 knockout mice. There were sex-specific differences in BDNF protein and mRNA expression, however. BDNF protein levels increased with age in female mice but not in males. And in females, but not males, ZnT3 KO mice exhibited great hippocampal BDNF mRNA expression than wild type mice. We conclude that, at least in naïve mice housed under standard laboratory conditions, elimination of vesicular zinc does not affect BDNF or TrkB protein levels.
在某些神经元中，锌离子通过锌转运蛋白 3（ZnT3）储存在突触小泡中。然后，囊泡中的锌可以被释放到突触中，以调节众多靶点。体外证据表明，这些靶点可能包括脑源性神经营养因子（BDNF）及其受体，原肌球蛋白受体激酶 B（TrkB）。但是，完整大脑中囊泡锌对 BDNF 和 TrkB 的影响尚不清楚。缺乏 ZnT3（因此缺乏囊泡锌）的小鼠研究表明 BDNF 和 TrkB 水平异常，但结果喜忧参半，因此难以解释。这可能是由于测试的小鼠在年龄或性别上存在差异。在本研究中，我们比较了不同年龄（5 周和 12 周）的雄性和雌性野生型和 ZnT3 敲除小鼠的海马体和新皮层中的 BDNF 和 TrkB 水平，并检查了中间年龄（8-10 周）的 BDNF mRNA 表达和蛋白水平。我们发现，无论年龄或性别如何，野生型和 ZnT3 敲除小鼠的 BDNF 和 TrkB 蛋白水平均无差异。然而，BDNF 蛋白和 mRNA 表达存在性别特异性差异。BDNF 蛋白水平在雌性小鼠中随年龄增长而增加，但在雄性小鼠中则不然。而且，在雌性小鼠中，但不在雄性小鼠中，ZnT3 KO 小鼠的海马体 BDNF mRNA 表达水平高于野生型小鼠。我们得出结论，至少在标准实验室条件下饲养的未成熟小鼠中，消除囊泡锌不会影响 BDNF 或 TrkB 蛋白水平。
