Instituto Cajal, CSIC, Madrid, Spain.
Laboratorio Cajal de Circuitos Corticales, Centro de Tecnología Biomédica (CTB), Universidad Politécnica de Madrid, Pozuelo de Alarcón, 28223, Madrid, Spain.
Brain Struct Funct. 2018 Dec;223(9):4307-4321. doi: 10.1007/s00429-018-1753-7. Epub 2018 Sep 15.
Mammalian hibernation is a natural process in which the brain undergoes profound adaptive changes that appear to protect the brain from extreme hypoxia and hypothermia. In addition to a virtual cessation of neural and metabolic activity, these changes include a decrease in adult neurogenesis; the retraction of neuronal dendritic trees; changes in dendritic spines and synaptic connections; fragmentation of the Golgi apparatus; and the phosphorylation of the microtubule-associated protein tau. Furthermore, alterations of microglial cells also occur in torpor. Importantly, all of these changes are rapidly and fully reversed when the animals arouse from torpor state, with no apparent brain damage occurring. Thus, hibernating animals are excellent natural models to study different aspects of brain plasticity. The axon initial segment (AIS) is critical for the initiation of action potentials in neurons and is an efficient site for the regulation of neural activity. This specialized structure-characterized by the expression of different types of ion channels and adhesion, scaffolding and cytoskeleton proteins-is subjected to morpho-functional plastic changes upon variations in neural activity or in pathological conditions. Here, we used immunocytochemistry and 3D confocal microscopy reconstruction techniques to measure the possible morphological differences in the AIS of neocortical (layers II-III and V) and hippocampal (CA1) neurons during the hibernation of the Syrian hamster. Our results indicate that the general integrity of the AIS is resistant to the ischemia/hypoxia conditions that are characteristic of the torpor phase of hibernation. In addition, the length of the AIS significantly increased in all the regions studied-by about 16-20% in torpor animals compared to controls, suggesting the existence of compensatory mechanisms in response to a decrease in neuronal activity during the torpor phase of hibernation. Furthermore, in double-labeling experiment, we found that the AIS in layer V of torpid animals was longer in neurons expressing phospho-tau than in those not labeled for phospho-tau. This suggests that AIS plastic changes were more marked in phospho-tau accumulating neurons. Overall, the results further emphasize that mammalian hibernation is a good physiological model to study AIS plasticity mechanisms in non-pathological conditions.
哺乳动物冬眠是一种自然过程，在此过程中，大脑会发生深刻的适应性变化，似乎能保护大脑免受极端缺氧和低温的影响。除了神经和代谢活动几乎停止外，这些变化还包括成年神经发生减少；神经元树突回缩；树突棘和突触连接变化；高尔基器碎片化；微管相关蛋白 tau 的磷酸化。此外，在蛰伏中也会发生小胶质细胞的改变。重要的是，当动物从蛰伏状态中醒来时，所有这些变化都会迅速而完全逆转，而且没有明显的脑损伤发生。因此，冬眠动物是研究大脑可塑性不同方面的极好的天然模型。轴突起始段（AIS）对于神经元动作电位的起始至关重要，并且是神经活动调节的有效部位。这个特殊的结构-其特征是表达不同类型的离子通道以及黏附、支架和细胞骨架蛋白-在神经活动变化或病理条件下会发生形态和功能上的可塑性变化。在这里，我们使用免疫细胞化学和 3D 共聚焦显微镜重建技术来测量叙利亚仓鼠冬眠期间新皮层（II-III 层和 V 层）和海马（CA1）神经元 AIS 可能存在的形态差异。我们的结果表明，AIS 的整体完整性能够抵抗冬眠蛰伏期特有的缺血/缺氧条件。此外，AIS 的长度在所有研究区域都显著增加-在蛰伏动物中比对照动物增加约 16-20%，这表明在冬眠蛰伏期神经活动减少时存在补偿机制。此外，在双标记实验中，我们发现蛰伏动物 V 层中表达磷酸化 tau 的神经元的 AIS 比未标记磷酸化 tau 的神经元更长。这表明 AIS 可塑性变化在磷酸化 tau 积累神经元中更为明显。总的来说，这些结果进一步强调了哺乳动物冬眠是研究非病理性条件下 AIS 可塑性机制的良好生理模型。
