Changes in the Extracellular Matrix with Aging: A Larger Role in Alzheimer's Disease DOI Creative Commons
Kathryn R. Jacobson,

Hailong Song

Journal of Neuroscience, Год журнала: 2024, Номер 44(22), С. e0081242024 - e0081242024

Опубликована: Май 29, 2024

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia (2023). Aging leading risk factor for sporadic onset AD. During normal aging, regulatory signaling pathways that are critical cellular health gradually become less effective, to impairment physiological functions across all tissue systems (Zia et al., 2021). For example, in healthy brain, production clearance amyloid-β (Aβ) peptides balanced maintain appropriate levels Aβ cells, vasculature, extracellular space. However, with body loses ability this process, an increase misfolded generation plaques (Hampel These one characteristic pathological features Insulin/insulin growth factor-1 (IGF-1) signaling, major pathway implicated regulation may also play pivotal role pathogenesis (Sano 2023). Insulin begins when insulin secreted by pancreas binds IGF-1 receptor, phosphorylation receptor substrate proteins, IRS1-4 modified substrates independently control distinct intracellular cascades. Genetic deletion these substrates, Irs2 , mice causes severe type 2 diabetes mellitus, associated behavioral changes, impairments … Correspondence should be addressed Kathryn R. Jacobson at kathryn.jacobson{at}pennmedicine.upenn.edu or Hailong Song hailong.song{at}pennmedicine.upenn.edu.

Язык: Английский

Mechanical and Functional Responses in Astrocytes under Alternating Deformation Modes Using Magneto‐Active Substrates DOI Creative Commons
Clara Gomez‐Cruz, Miguel Fernández-de la Torre, Dariusz Lachowski

и другие.

Advanced Materials, Год журнала: 2024, Номер 36(26)

Опубликована: Апрель 13, 2024

This work introduces NeoMag, a system designed to enhance cell mechanics assays in substrate deformation studies. NeoMag uses multidomain magneto-active materials mechanically actuate the substrate, transmitting reversible mechanical cues cells. The boasts full flexibility alternating loading modes, seamlessly adapting both upright and inverted microscopes. substrates facilitate mechanobiology on 2D 3D cultures. integration of with nanoindenters allows for precise evaluation cellular properties under varying modes. is used study impact astrocytes, simulating conditions akin traumatic brain injury ischemic stroke. results reveal local heterogeneous changes astrocyte stiffness, influenced by orientation subcellular regions relative strain. These stiffness variations, exceeding 50% stiffening softening, deformations significantly alter calcium dynamics. Furthermore, sustained induce actin network reorganization activate Piezo1 channels, leading an initial increase followed long-term inhibition events. Conversely, fast dynamic transiently channels disrupt network, causing softening. findings unveil functional alterations astrocytes during deformation, illustrating multiple opportunities this technology offers.

Язык: Английский

Процитировано

21
Stress landscape of folding brain serves as a map for axonal pathfinding DOI Creative Commons

Akbar Solhtalab,

Ali H. Foroughi,

Lana Pierotich

и другие.

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 30, 2025

Abstract Understanding the mechanics linking cortical folding and brain connectivity is crucial for both healthy abnormal development. Despite importance of this relationship, existing models fail to explain how growing axon bundles navigate stress field within a or bidirectional dynamic interaction shapes resulting surface morphologies patterns. Here, we propose concept “axon reorientation” formulate mechanical model uncover multiscale linkages between Simulations incorporating bundle reorientation stress-induced growth reveal potential mechanisms that lead higher density in gyri (ridges) compared sulci (valleys). In particular, patterning from exhibits strong dependence on rate properties navigating bundles. Model predictions are supported by vivo diffusion tensor imaging human brain.

Язык: Английский

Процитировано

3
Investigation of PLA/ZnO Nanofibers for Piezoelectric and Nerve Regeneration Applications DOI
Meysam Moezzi, Meghdad Kamali Moghaddam,

Jafar Rahimzadeh

и другие.

Sensors and Actuators A Physical, Год журнала: 2025, Номер unknown, С. 116340 - 116340

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

1
The Role of Mechanotransduction in Contact Inhibition of Locomotion and Proliferation DOI Open Access
Fumihiko Nakamura

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(4), С. 2135 - 2135

Опубликована: Фев. 10, 2024

Contact inhibition (CI) represents a crucial tumor-suppressive mechanism responsible for controlling the unbridled growth of cells, thus preventing formation cancerous tissues. CI can be further categorized into two distinct yet interrelated components: locomotion (CIL) and proliferation (CIP). These components have historically been viewed as separate processes, but emerging research suggests that they may regulated by both shared pathways. Specifically, recent studies indicated CIP CIL utilize mechanotransduction pathways, process involves cells sensing responding to mechanical forces. This review article describes role in CI, shedding light on how forces regulate CIP. Emphasis is placed filamin A (FLNA)-mediated mechanotransduction, elucidating FLNA senses translates them biochemical signals cell proliferation. In addition FLNA, trans-acting factors (TAFs), which are proteins or regulatory RNAs capable directly indirectly binding specific DNA sequences distant genes gene expression, emerge sensitive players signaling pathways CI. presents methods identifying these TAF profiling associated changes chromatin structure, offering valuable insights other biological functions mediated mechanotransduction. Finally, it addresses unanswered questions fields delineates their possible future directions.

Язык: Английский

Процитировано

8
The Networking Brain: How Extracellular Matrix, Cellular Networks, and Vasculature Shape the In Vivo Mechanical Properties of the Brain DOI Creative Commons
Judith Bergs, Anna S. Morr, Rafaela V. Silva

и другие.

Advanced Science, Год журнала: 2024, Номер 11(31)

Опубликована: Июнь 14, 2024

Abstract Mechanically, the brain is characterized by both solid and fluid properties. The resulting unique material behavior fosters proliferation, differentiation, repair of cellular vascular networks, optimally protects them from damaging shear forces. Magnetic resonance elastography (MRE) a noninvasive imaging technique that maps mechanical properties in vivo. MRE studies have shown abnormal processes such as neuronal degeneration, demyelination, inflammation, leakage lead to tissue softening. In contrast, network formation, higher pressure result stiffening. addition, viscosity has been reported change with normal blood perfusion variability maturation well disease conditions tumor invasion. this article, contributions neuronal, glial, extracellular, networks are discussed coarse‐grained parameters determined MRE. This reductionist multi‐network model mechanics helps explain many observations terms microanatomical changes suggests cerebral viscoelasticity suitable marker for disease.

Язык: Английский

Процитировано

6
Cytoskeleton-modulating nanomaterials and their therapeutic potentials DOI
Jin-Won Park,

Yina Wu,

Jung Suk Kim

и другие.

Advanced Drug Delivery Reviews, Год журнала: 2024, Номер 211, С. 115362 - 115362

Опубликована: Июнь 19, 2024

Язык: Английский

Процитировано

4
Naturally occurring, rostrally conjoining chicken twins attempt to make a forebrain DOI Creative Commons
F. Schubert, Susanne Dietrich

Developmental Biology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0
Intellectual Property Rights in Neuroprotective Biomaterials DOI
Chandrabhan Prajapati, Prabhash Nath Tripathi,

Saloni Sood

и другие.

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0
3D In Vitro Glioma‐Neuron‐Astrocyte Biomimetic Composites Recapitulate Key Molecular Mechanisms Linked to Glioblastoma Multiforme Pathophysiology DOI Creative Commons

Mateo S. Andrade Mier,

Esra Türker, Jessica Faber

и другие.

Advanced Functional Materials, Год журнала: 2025, Номер unknown

Опубликована: Янв. 23, 2025

Abstract Glioblastoma multiforme is the most devastating brain tumor without cure. Although in vitro and vivo research on glioblastoma have demonstrated its complexity, including interactions with cells microenvironment, 3D models resembling those key features allowing to study therapeutic interventions of this aggressive are scarce. Here, a model developed that establishes microenvironment hyaluronic acid‐based hydrogel cross‐linked laminin, both which components brain's extracellular matrix. This mimics mechanical properties matrix at macroscopic mesoscopic levels, as evaluated by stiffness, viscosity using rheological nanoindentation measurements. The ultra‐soft storage modulus 100 Pa reinforced printed microfiber scaffolds allow setup multicellular primary cortical neurons astrocytes cells. Tumor characterized through confocal shadow imaging disease entities functional surrounding tumor's hijacking capability neuronal signaling promote own proliferation.

Язык: Английский

Процитировано

0
Measurement force, speed and post-mortem time affect the ratio of CNS grey to white matter elasticity DOI Creative Commons
Julia Becker, Alexander Winkel, Eva Kreysing

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 30, 2025

Abstract For several decades, many attempts have been made to characterise the mechanical properties of grey and white matter, which constitute two main compartments central nervous system (CNS), with various methods contradictory results. In particular, ratio grey-to-white-matter elasticity is sometimes larger than 1 smaller; reason for this apparent discrepancy currently unknown. Here, we exploited atomic force microscopy (AFM)-based indentation measurements systematically investigate how measurement force, speed, post-mortem interval temperature affect measured spinal cord tissue, in particular ( K g /K w ). Within explored parameter space, increasing speed increased both matter. However, declined from values as high ∼5 at low forces speeds ∼1 speeds. also strongly depended on anatomical plane were conducted was considerably higher transverse sections compared longitudinal sections. Furthermore, impacted absolute tissue . Grey matter started decreasing ∼3 hours until reaching a plateau after ∼6 hours. contrast, declining beginning post-mortem, when it levelled off. As result, before stabilising. Between 20°C 38°C, decreased similar rate, without affecting We thus identified differences response varying strains strain rates, interval, excluded factor These differential responses likely contribute results obtained different working regimes. Statement significance here showed that CNS an applied differentially depends parameters such magnitude forces, well axis along are conducted. broaden our understanding mechanics pave way better more targeted experimental design future experiments. Ultimately, they may help reconcile seemingly literature concerning elasticity.

Язык: Английский

Процитировано

0