Brain-derived neurotrophic factor, phosphorylated cyclic AMP response element binding protein and neuropeptide Y decline as early as middle age in the dentate gyrus and CA1 and CA3 subfields of the hippocampus
Brain-derived neurotrophic factor, phosphorylated cyclic AMP response element binding protein and neuropeptide Y decline as early as middle age in the dentate gyrus and CA1 and CA3 subfields of the hippocampus
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DOI：
10.1016/j.expneurol.2005.05.014
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发表时间：
2005-10-01
影响因子：
5.3
通讯作者：
Shetty, AK
中科院分区：
文献类型：
--
作者：
Hattiangady, B;Rao, MS;Shetty, AK
海马体很容易老化。中年时齿状核神经发生的严重减少是衰老海马中最明显的早期变化之一，这可能与影响神经发生的神经营养因子和信号蛋白浓度的早期下降有关。我们分析了三种蛋白质，众所周知，以促进齿状回和海马CA 1和CA 3亚区的年轻，中年和老年F344大鼠的齿状回神经发生和学习记忆功能。这些包括脑源性神经营养因子（BDNF），转录因子磷酸化环AMP反应元件结合蛋白（p-CREB）和神经肽神经肽Y（NPY）。通过ELISA和BDNF免疫组织化学分析BDNF，通过p-CREB免疫阳性细胞的光密度分析p-CREB，通过NPY免疫阳性中间神经元的体视学计数分析NPY。我们提供了新的证据，BDNF浓度，p-CREB免疫反应性和NPY免疫阳性interneurons的数量下降相当大的中年在齿状回和海马CA 1和CA 3亚区。然而，BDNF浓度和NPY免疫阳性中间神经元数量在中年和老年之间没有显着减少。相反，在此期间，p-CREB免疫反应性进一步减少，这也与齿状回颗粒细胞和海马锥体神经元的索马内BDNF免疫反应减少有关。总的来说，这些结果表明，在中年时观察到的严重抑制的齿状神经发生至少部分与BDNF、p-CREB和NPY浓度降低有关，因为这些蛋白质中的每一种都是齿状神经发生的正调节剂。老年时CREB磷酸化的显著减少（以及BDNF和NPY水平的持续降低）可能是衰老期间观察到的学习和记忆障碍的基础。(c)2005年爱思唯尔公司All rights reserved.
The hippocampus is very susceptible to aging. Severely diminished dentate neurogenesis at middle age is one of the most conspicuous early changes in the aging hippocampus, which is likely linked to an early decline in the concentration of neurotrophic factors and signaling proteins that influence neurogenesis. We analyzed three proteins that are well-known to promote dentate neurogenesis and learning and memory function in the dentate gyrus and the hippocampal CA1 and CA3 subfields of young, middle-aged and aged F344 rats. These include the brain-derived neurotrophic factor (BDNF), the transcription factor phosphorylated cyclic AMP response element binding protein (p-CREB) and the neuropeptide neuropeptide Y (NPY). The BDNF was analyzed via ELISA and BDNF immunohistochemistry, the p-CREB through densitometric analysis of p-CREB immunopositive cells, and the NPY via stereological counting of NPY-immunopositive interneurons. We provide new evidence that the BDNF concentration, the p-CREB immunoreactivity and the number of NPY immunopositive interneurons decline considerably by middle age in both dentate gyrus and CA1 and CA3 subfields of the hippocampus. However, both BDNF concentration and NPY immunopositive interneuron numbers exhibit no significant decrease between middle age and old age. In contrast, the p-CREB immunoreactivity diminishes further during this period, which is also associated with reduced BDNF immunoreaction within the soma of dentate granule cells and hippocampal pyramidal neurons. Collectively, these results suggest that severely dampened dentate neurogenesis observed at middle age is linked at least partially to reduced concentrations of BDNF, p-CREB and NPY, as each of these proteins is a positive regulator of dentate neurogenesis. Dramatically diminished CREB phosphorylation (and persistently reduced levels of BDNF and NPY) at old age may underlie the learning and memory impairments observed during senescence. (c) 2005 Elsevier Inc. All rights reserved.