Department of Anesthesiology, Jing'an District Central Hospital of Shanghai, Shanghai, China.
Department of Anesthesiology, Shanghai Public Health Clinical Center, Shanghai, China.
CNS Neurosci Ther. 2022 May;28(5):761-774. doi: 10.1111/cns.13809. Epub 2022 Feb 3.
Hypoxia and inflammation may lead to BDNF/TrkB dysregulation and neurological disorders. Propofol is an anesthetic with neuroprotective properties. We wondered whether and how propofol affected BDNF/TrkB pathway in hippocampal neurons and astrocytes.
Primary rat hippocampal neurons and astrocytes were cultured and exposed to propofol followed by hypoxia or TNF-α treatment. The expression of BDNF and the expression/truncation/phosphorylation of TrkB were measured. The underlying mechanisms were investigated.
Hypoxia and TNF-α reduced the expression of BDNF, which was reversed by pretreatment of 25 μM propofol in hippocampal neurons. Furthermore, hypoxia and TNF-α increased the phosphorylation of ERK and phosphorylation of CREB at Ser142, while reduced the phosphorylation of CREB at Ser133, which were all reversed by 25 μM propofol and 10 μM ERK inhibitor. In addition, hypoxia or TNF-α did not affect TrkB expression, truncation, or phosphorylation in hippocampal neurons and astrocytes. However, in hippocampal neurons, 50 μM propofol induced TrkB phosphorylation, which may be mediated by p35 expression and Cdk5 activation, as suggested by the data showing that blockade of p35 or Cdk5 expression mitigated propofol-induced TrkB phosphorylation.
Propofol modulated BDNF/TrkB pathway in hippocampal neurons via ERK/CREB and p35/Cdk5 under the condition of hypoxia or TNF-α exposure.
缺氧和炎症可能导致 BDNF/TrkB 失调和神经紊乱。异丙酚是一种具有神经保护作用的麻醉剂。我们想知道异丙酚是否以及如何影响海马神经元和星形胶质细胞中的 BDNF/TrkB 通路。
原代培养大鼠海马神经元和星形胶质细胞，并用异丙酚预处理，然后进行缺氧或 TNF-α 处理。测量 BDNF 的表达以及 TrkB 的表达/截断/磷酸化。研究了潜在的机制。
缺氧和 TNF-α 降低了 BDNF 的表达，而 25μM 异丙酚预处理可逆转这一现象。此外，缺氧和 TNF-α 增加了 ERK 的磷酸化和 CREB 在 Ser142 的磷酸化，而降低了 CREB 在 Ser133 的磷酸化，这些都被 25μM 异丙酚和 10μM ERK 抑制剂逆转。此外，缺氧或 TNF-α 不影响海马神经元和星形胶质细胞中 TrkB 的表达、截断或磷酸化。然而，在海马神经元中，50μM 异丙酚诱导了 TrkB 的磷酸化，这可能是由 p35 表达和 Cdk5 激活介导的，因为数据表明，阻断 p35 或 Cdk5 的表达减轻了异丙酚诱导的 TrkB 磷酸化。
在缺氧或 TNF-α 暴露的情况下，异丙酚通过 ERK/CREB 和 p35/Cdk5 调节海马神经元中的 BDNF/TrkB 通路。
