Department of Mechanical Engineering, University College London, London, UK.
School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton, UK.
Eur J Neurosci. 2021 Jun;53(12):3851-3878. doi: 10.1111/ejn.14766. Epub 2020 May 18.
Just as the epigenome, the proteome and the electrophysiological properties of a cell influence its function, so too do its intrinsic mechanical properties and its extrinsic mechanical environment. This is especially true for neurons of the central nervous system (CNS) as long-term maintenance of synaptic connections relies on efficient axonal transport machinery and structural stability of the cytoskeleton. Recent reports suggest that profound physical changes occur in the CNS microenvironment with advancing age which, in turn, will impact highly mechanoresponsive neurons and glial cells. Here, we discuss the complex and inhomogeneous mechanical structure of CNS tissue, as revealed by recent mechanical measurements on the brain and spinal cord, using techniques such as magnetic resonance elastography and atomic force microscopy. Moreover, ageing, traumatic brain injury, demyelination and neurodegeneration can perturb the mechanical properties of brain tissue and trigger mechanobiological signalling pathways in neurons, glia and cerebral vasculature. It is, therefore, very likely that significant changes in cell and tissue mechanics contribute to age-related cognitive decline and deficits in memory formation which are accelerated and magnified in neurodegenerative states, such as Alzheimer's disease. Importantly, we are now beginning to understand how neuronal and glial cell mechanics and brain tissue mechanobiology are intimately linked with neurophysiology and cognition.
正如细胞的表观基因组、蛋白质组和电生理特性影响其功能一样，细胞的固有机械特性及其外在的机械环境也是如此。中枢神经系统 (CNS) 的神经元尤其如此，因为突触连接的长期维持依赖于有效的轴突运输机制和细胞骨架的结构稳定性。最近的报告表明，随着年龄的增长，CNS 微环境会发生深刻的物理变化，这反过来又会影响高度机械敏感的神经元和神经胶质细胞。在这里，我们讨论了最近在大脑和脊髓上使用磁共振弹性成像和原子力显微镜等技术进行的机械测量所揭示的 CNS 组织的复杂和不均匀的机械结构。此外，衰老、创伤性脑损伤、脱髓鞘和神经退行性变会破坏脑组织的机械性能，并在神经元、神经胶质和脑血管中引发机械生物学信号通路。因此，细胞和组织力学的显著变化极有可能导致与年龄相关的认知能力下降和记忆形成缺陷，而在神经退行性疾病状态下，如阿尔茨海默病，这些缺陷会加速和放大。重要的是，我们现在开始了解神经元和神经胶质细胞力学以及脑组织的机械生物学如何与神经生理学和认知密切相关。
