Abstract:The lineage commitment of many cultured stem cells, including adult neural stem cells (NSCs), is strongly sensitive to the stiffness of the underlying extracellular matrix. However, it remains unclear how well the stiffness ranges explored in culture align with the microscale stiffness values stem cells actually encounter within their endogenous tissue niches. To address this question in the context of hippocampal NSCs, we used atomic force microscopy to spatially map the microscale elastic modulus (E) of spec… Show more
“…However, our findings are in contrast with previous studies, which found a positive correlation between stiffness and cell nucleus area on the spinal cord of the adult mouse, retina of the ruminant and embryonic brain of Xenopus [3,30,32]. Furthermore, granular cell layer in coronal hippocampal slices of the juvenile rats was also shown to be stiffer than hilus [21]. While different CNS tissue composition might be the reason for the discrepancy between our results and those reported in the literature, it is worth stressing that our indentation protocol significantly differs with respect to that used in previous studies.…”
Section: Discussioncontrasting
confidence: 99%
“…It is therefore commonly agreed that a deep knowledge of the correlation between brain composition and mechanical properties of the tissue would enable neuroscientists to shed light on how mechanotransduction phenomena contribute to the functioning of the brain. Furthermore, a quantitative assessment of the viscoelasticity characteristics of the different regions of the brain could pave the way for the improvement of computational brain injury models [15], the engineering of brain phantoms for surgical practise [16,17], the design of mechanically matched brain implants [18], and the production of soft substrates that could mimic different mechanical environments for investigations of stiffness-dependent neural stem cell differentiation [19][20][21] and neuronal and glial cell morphology [22]. Yet, at present, the relation between mechanical properties and cytoarchitecture is still largely unknown.…”
The mechanical properties of brain tissue play a pivotal role in neurodevelopment and neurological disorders. Yet, at present, there is no consensus on how the different structural parts of the tissue contribute to its stiffness variations. Here, we have gathered depth-controlled indentation viscoelasticity maps of the hippocampus of acute horizontal live mouse brain slices. Our results confirm the highly viscoelestic nature of brain tissue. We further show that the mechanical properties are non-uniform and at least related to differences in morphological composition. Interestingly, areas with higher nuclear density appear to be softer than areas with lower nuclear density.
“…However, our findings are in contrast with previous studies, which found a positive correlation between stiffness and cell nucleus area on the spinal cord of the adult mouse, retina of the ruminant and embryonic brain of Xenopus [3,30,32]. Furthermore, granular cell layer in coronal hippocampal slices of the juvenile rats was also shown to be stiffer than hilus [21]. While different CNS tissue composition might be the reason for the discrepancy between our results and those reported in the literature, it is worth stressing that our indentation protocol significantly differs with respect to that used in previous studies.…”
Section: Discussioncontrasting
confidence: 99%
“…It is therefore commonly agreed that a deep knowledge of the correlation between brain composition and mechanical properties of the tissue would enable neuroscientists to shed light on how mechanotransduction phenomena contribute to the functioning of the brain. Furthermore, a quantitative assessment of the viscoelasticity characteristics of the different regions of the brain could pave the way for the improvement of computational brain injury models [15], the engineering of brain phantoms for surgical practise [16,17], the design of mechanically matched brain implants [18], and the production of soft substrates that could mimic different mechanical environments for investigations of stiffness-dependent neural stem cell differentiation [19][20][21] and neuronal and glial cell morphology [22]. Yet, at present, the relation between mechanical properties and cytoarchitecture is still largely unknown.…”
The mechanical properties of brain tissue play a pivotal role in neurodevelopment and neurological disorders. Yet, at present, there is no consensus on how the different structural parts of the tissue contribute to its stiffness variations. Here, we have gathered depth-controlled indentation viscoelasticity maps of the hippocampus of acute horizontal live mouse brain slices. Our results confirm the highly viscoelestic nature of brain tissue. We further show that the mechanical properties are non-uniform and at least related to differences in morphological composition. Interestingly, areas with higher nuclear density appear to be softer than areas with lower nuclear density.
“…For example, some of the studies used tips with the radius of 250 µm resulting in contact area much larger than individual anatomical regions of hippocampus and thus measuring averaged mechanical properties over multiple layers [16,17,18,19,25,26,27,22,44]. Other studies used smaller tips and indentation depths (R < 20 µm, h < 4 µm [28,45,46]), where reported relative differences between regions do not agree with our findings.…”
Section: Viscoelastic Mapping Of Hippocampus and Cerebellumcontrasting
There is growing evidence that mechanical factors affect brain functioning. However, brain components responsible for regulating the physiological mechanical environment and causing mechanical alterations during maturation are not completely understood. To determine the relationship between structure and stiffness of the brain tissue, we performed high resolution viscoelastic mapping by dynamic indentation of hippocampus and cerebellum of juvenile brain, and quantified relative area covered by immunohistochemical staining of NeuN (neurons), GFAP (astrocytes), Hoechst (nuclei), MBP (myelin), NN18 (axons) of juvenile and adult mouse brain slices. When compared the mechanical properties of juvenile mouse brain slices with previously obtained data on adult slices, the latter was ∼ 20-150% stiffer, which correlates with an increase in the relative area covered by astrocytes. Heterogeneity within the slice, in terms of storage modulus, correlates negatively with the relative area of nuclei and neurons, as well as myelin and axons, while the relative area of astrocytes correlates positively. Several linear regression models are suggested to predict the mechanical properties of the brain tissue based on immunohistochemical stainings.
“…To examine the impact of stiffness on NSC behavior, the Schaffer and Healy laboratories developed synthetic hydrogel culture systems with variable elastic moduli and found that modulus strongly influences neuronal vs. astrocytic differentiation of adult hippocampal NSCs, with softer gels favoring neurons and harder gels promoting astrocytes (Saha et al 2008). In addition, the hippocampal NSC niche has local stiffness gradients (Luque et al 2016). Though changes in brain stiffness have been attributed to pathology associated with neurodegeneration, cancer, and acute injuries that cause glial scarring, the reported research on brain stiffness parameters in elderly individuals is more limited, with most age-related studies focusing on early development versus young adult brains.…”
The genesis of new neurons from neural stem cells in the adult brain offers the hope that this mechanism of plasticity can be harnessed for the treatment of brain injuries and diseases. However, neurogenesis becomes impaired during the normal course of aging; this is also the primary risk factor for most neurodegenerative diseases. The local microenvironment that regulates the function of resident neural stem cells (the "neurogenic niche") is a particularly complex network of various signaling mechanisms, rendering it especially challenging for the dissection of the control of these cells but offering the potential for the advancement of our understanding of the regulation/misregulation of neurogenesis. In this review, we examine the factors that control neurogenesis in an age-dependent manner, and we define these signals by the extrinsic mechanism through which they are presented to the neural stem cells. Secreted signals, cell-contact-dependent signals, and extracellular matrix cues all contribute to the regulation of the aging neurogenic niche and offer points of therapeutic intervention.
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