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The sphingosine 1‐phosphate analogue, FTY720, modulates the lipidomic signature of the mouse hippocampus (2024)
Journal Article
Magalhães, D. M., Stewart, N. A., Mampay, M., Rolle, S. O., Hall, C. M., Moeendarbary, E., …Sheridan, G. K. (in press). The sphingosine 1‐phosphate analogue, FTY720, modulates the lipidomic signature of the mouse hippocampus. Journal of Neurochemistry, https://doi.org/10.1111/jnc.16073

The small‐molecule drug, FTY720 (fingolimod), is a synthetic sphingosine 1‐phosphate (S1P) analogue currently used to treat relapsing–remitting multiple sclerosis in both adults and children. FTY720 can cross the blood–brain barrier (BBB) and, over t... Read More about The sphingosine 1‐phosphate analogue, FTY720, modulates the lipidomic signature of the mouse hippocampus.

Age-related impact of social isolation in mice: Young vs middle-aged (2024)
Journal Article
Magalhães, D. M., Mampay, M., Sebastião, A. M., Sheridan, G. K., & Valente, C. A. (2024). Age-related impact of social isolation in mice: Young vs middle-aged. Neurochemistry International, 174, Article 105678. https://doi.org/10.1016/j.neuint.2024.105678

Social isolation is a chronic mild stressor and a significant risk factor for mental health disorders. Herein we explored the impact of social isolation on depression- and anxiety-like behaviours, as well as spatial memory impairments, in middle-aged... Read More about Age-related impact of social isolation in mice: Young vs middle-aged.

Emergent mechanical control of vascular morphogenesis (2023)
Journal Article
Whisler, J., Shahreza, S., Schlegelmilch, K., Ege, N., Javanmardi, Y., Malandrino, A., …Moeendarbary, E. (2023). Emergent mechanical control of vascular morphogenesis. Science Advances, 9(32), Article eadg9781. https://doi.org/10.1126/sciadv.adg9781

Vascularization is driven by morphogen signals and mechanical cues that coordinately regulate cellular force generation, migration, and shape change to sculpt the developing vascular network. However, it remains unclear whether developing vasculature... Read More about Emergent mechanical control of vascular morphogenesis.

Hippocampus of the APP NL–G–F mouse model of Alzheimer’s disease exhibits region-specific tissue softening concomitant with elevated astrogliosis (2023)
Journal Article
Hall, C. M., Lasli, S., Serwinski, B., Djordjevic, B., Sheridan, G. K., & Moeendarbary, E. (2023). Hippocampus of the APP NL–G–F mouse model of Alzheimer’s disease exhibits region-specific tissue softening concomitant with elevated astrogliosis. Frontiers in Aging Neuroscience, 15, Article 1212212. https://doi.org/10.3389/fnagi.2023.1212212

Widespread neurodegeneration, enlargement of cerebral ventricles, and atrophy of cortical and hippocampal brain structures are classic hallmarks of Alzheimer’s disease (AD). Prominent macroscopic disturbances to the cytoarchitecture of the AD brain o... Read More about Hippocampus of the APP NL–G–F mouse model of Alzheimer’s disease exhibits region-specific tissue softening concomitant with elevated astrogliosis.

Endothelium and Subendothelial Matrix Mechanics Modulate Cancer Cell Transendothelial Migration (2023)
Journal Article
Javanmardi, Y., Agrawal, A., Malandrino, A., Lasli, S., Chen, M., Shahreza, S., …Kamm, R. (2023). Endothelium and Subendothelial Matrix Mechanics Modulate Cancer Cell Transendothelial Migration. Advanced Science, 10(16), Article 2206554. https://doi.org/10.1002/advs.202206554

Cancer cell extravasation, a key step in the metastatic cascade, involves cancer cell arrest on the endothelium, transendothelial migration (TEM), followed by the invasion into the subendothelial extracellular matrix (ECM) of distant tissues. While c... Read More about Endothelium and Subendothelial Matrix Mechanics Modulate Cancer Cell Transendothelial Migration.

Poroelastic osmoregulation of living cell volume (2021)
Journal Article
Esteki, M. H., Malandrino, A., Alemrajabi, A. A., Sheridan, G. K., Charras, G., & Moeendarbary, E. (2021). Poroelastic osmoregulation of living cell volume. iScience, 24(12), Article 103482. https://doi.org/10.1016/j.isci.2021.103482

Cells maintain their volume through fine intracellular osmolarity regulation. Osmotic challenges drive fluid into or out of cells causing swelling or shrinkage, respectively. The dynamics of cell volume changes depending on the rheology of the cellul... Read More about Poroelastic osmoregulation of living cell volume.

Tumour brain: pre‐treatment cognitive and affective disorders caused by peripheral cancers (2021)
Journal Article
Mampay, M., Flint, M. S., & Sheridan, G. K. (2021). Tumour brain: pre‐treatment cognitive and affective disorders caused by peripheral cancers. British Journal of Pharmacology, 178(19), 3977-3996. https://doi.org/10.1111/bph.15571

People that develop extracranial cancers often display co-morbid neurological disorders, such as anxiety, depression and cognitive impairment, even before commencement of chemotherapy. This suggests bidirectional crosstalk between non-CNS tumours and... Read More about Tumour brain: pre‐treatment cognitive and affective disorders caused by peripheral cancers.

Extracellular Vesicles and Intercellular Communication in the Central Nervous System (2021)
Journal Article
Lizarraga‐Valderrama, L. R., & Sheridan, G. K. (2021). Extracellular Vesicles and Intercellular Communication in the Central Nervous System. FEBS Letters, 595(10), 1391-1410. https://doi.org/10.1002/1873-3468.14074

Neurons and glial cells of the central nervous system (CNS) release extracellular vesicles (EVs) to the interstitial fluid of the brain and spinal cord parenchyma. EVs contain proteins, nucleic acids and lipids that can be taken up by, and modulate t... Read More about Extracellular Vesicles and Intercellular Communication in the Central Nervous System.

Spatiotemporal immunolocalisation of REST in the brain of healthy ageing and Alzheimer’s disease rats (2020)
Journal Article
Mampay, M., Velasco‐Estevez, M., Rolle, S. O., Chaney, A. M., Boutin, H., Dev, K. K., …Sheridan, G. K. (2021). Spatiotemporal immunolocalisation of REST in the brain of healthy ageing and Alzheimer’s disease rats. FEBS Open Bio, 11(1), 146-163. https://doi.org/10.1002/2211-5463.13036

In the brain, REST (Repressor Element‐1 Silencing Transcription factor) is a key regulator of neuron cell‐specific gene expression. Nuclear translocation of neuronal REST has been shown to be neuroprotective in a healthy ageing context. In contrast,... Read More about Spatiotemporal immunolocalisation of REST in the brain of healthy ageing and Alzheimer’s disease rats.

Mechanobiology of the brain in ageing and Alzheimer's disease (2020)
Journal Article
Hall, C. M., Moeendarbary, E., & Sheridan, G. K. (2021). Mechanobiology of the brain in ageing and Alzheimer's disease. European Journal of Neuroscience, 53(12), 3851-3878. https://doi.org/10.1111/ejn.14766

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 n... Read More about Mechanobiology of the brain in ageing and Alzheimer's disease.

A new framework for characterization of poroelastic materials using indentation (2019)
Journal Article
Esteki, M. H., Alemrajabi, A. A., Hall, C., Sheridan, G. K., Azadi, M., & Moeendarbary, E. (2020). A new framework for characterization of poroelastic materials using indentation. Acta Biomaterialia, 102, 138-148. https://doi.org/10.1016/j.actbio.2019.11.010

To characterize a poroelastic material, typically an indenter is pressed onto the surface of the material with a ramp of a finite approach velocity followed by a hold where the indenter displacement is kept constant. This leads to deformation of the... Read More about A new framework for characterization of poroelastic materials using indentation.

Inhibition of Piezo1 attenuates demyelination in the central nervous system (2019)
Journal Article
Velasco‐Estevez, M., Gadalla, K. K. E., Liñan‐Barba, N., Cobb, S., Dev, K. K., & Sheridan, G. K. (2020). Inhibition of Piezo1 attenuates demyelination in the central nervous system. Glia, 68(2), 356-375. https://doi.org/10.1002/glia.23722

Piezo1 is a mechanosensitive ion channel that facilitates the translation of extracellular mechanical cues to intracellular molecular signaling cascades through a process termed, mechanotransduction. In the central nervous system (CNS), mechanically... Read More about Inhibition of Piezo1 attenuates demyelination in the central nervous system.

Piezo1 regulates calcium oscillations and cytokine release from astrocytes (2019)
Journal Article
Sheridan, G. K., Velasco‐Estevez, M., Dev, K. K., Rolle, S. O., & Mampay, M. (2020). Piezo1 regulates calcium oscillations and cytokine release from astrocytes. Glia, 68(1), 145-160. https://doi.org/10.1002/glia.23709

Astrocytes are important for information processing in the brain and they achieve this by fine‐tuning neuronal communication via continuous uptake and release of biochemical modulators of neurotransmission and synaptic plasticity. Often overlooked ar... Read More about Piezo1 regulates calcium oscillations and cytokine release from astrocytes.

Spatiotemporally Super-Resolved Volumetric Traction Force Microscopy (2019)
Journal Article
Colin-York, H., Javanmardi, Y., Barbieri, L., Li, D., Korobchevskaya, K., Guo, Y., …Fritzsche, M. (2019). Spatiotemporally Super-Resolved Volumetric Traction Force Microscopy. Nano Letters, 19(7), 4427-4434. https://doi.org/10.1021/acs.nanolett.9b01196

Quantification of mechanical forces is a major challenge across biomedical sciences. Yet such measurements are essential to understanding the role of biomechanics in cell regulation and function. Traction force microscopy remains the most broadly app... Read More about Spatiotemporally Super-Resolved Volumetric Traction Force Microscopy.

REST: An epigenetic regulator of neuronal stress responses in the young and ageing brain (2019)
Journal Article
Mampay, M., & Sheridan, G. K. (2019). REST: An epigenetic regulator of neuronal stress responses in the young and ageing brain. Frontiers in Neuroendocrinology, 53, Article 100744. https://doi.org/10.1016/j.yfrne.2019.04.001

The transcriptional repressor REST (Repressor Element-1 Silencing Transcription factor)is a key modulator of the neuronal epigenome and targets genes involved in neuronal differentiation, axonal growth, vesicular transport, ion channel conductance an... Read More about REST: An epigenetic regulator of neuronal stress responses in the young and ageing brain.

Infection Augments Expression of Mechanosensing Piezo1 Channels in Amyloid Plaque-Reactive Astrocytes (2018)
Journal Article
Velasco-Estevez, M., Mampay, M., Boutin, H., Chaney, A., Warn, P., Sharp, A., …Sheridan, G. K. (2018). Infection Augments Expression of Mechanosensing Piezo1 Channels in Amyloid Plaque-Reactive Astrocytes. Frontiers in Aging Neuroscience, 10, Article 332. https://doi.org/10.3389/fnagi.2018.00332

© 2018 Velasco-Estevez, Mampay, Boutin, Chaney, Warn, Sharp, Burgess, Moeendarbary, Dev and Sheridan. A defining pathophysiological hallmark of Alzheimer's disease (AD) is the amyloid plaque; an extracellular deposit of aggregated fibrillar Aβ142 pep... Read More about Infection Augments Expression of Mechanosensing Piezo1 Channels in Amyloid Plaque-Reactive Astrocytes.

Sphingosine 1-phosphate receptors regulate TLR4-induced CXCL5 release from astrocytes and microglia (2018)
Journal Article
O'Sullivan, S. A., O'Sullivan, C., Healy, L. M., Dev, K. K., & Sheridan, G. K. (2018). Sphingosine 1-phosphate receptors regulate TLR4-induced CXCL5 release from astrocytes and microglia. Journal of Neurochemistry, 144(6), 736-747. https://doi.org/10.1111/jnc.14313

© 2018 International Society for Neurochemistry. Sphingosine 1-phosphate receptors (S1PR) are G protein-coupled and compose a family with five subtypes, S1P1R–S1P5R. The drug Gilenya ® (Novartis, Basel, Switzerland) (Fingolimod; FTY720) targets S1PRs... Read More about Sphingosine 1-phosphate receptors regulate TLR4-induced CXCL5 release from astrocytes and microglia.

The soft mechanical signature of glial scars in the central nervous system (2017)
Journal Article
Sheridan, G. K., Moeendarbary, E., Weber, I. P., Koser, D. E., Soleman, S., Haenzi, B., …Franze, K. (2017). The soft mechanical signature of glial scars in the central nervous system. Nature Communications, 8(1), Article 14787. https://doi.org/10.1038/ncomms14787

© The Author(s) 2017. Injury to the central nervous system (CNS) alters the molecular and cellular composition of neural tissue and leads to glial scarring, which inhibits the regrowth of damaged axons. Mammalian glial scars supposedly form a chemica... Read More about The soft mechanical signature of glial scars in the central nervous system.

Mechanosensing is critical for axon growth in the developing brain (2016)
Journal Article
Koser, D. E., Thompson, A. J., Foster, S. K., Dwivedy, A., Pillai, E. K., Sheridan, G. K., …Franze, K. (2016). Mechanosensing is critical for axon growth in the developing brain. Nature Neuroscience, 19(12), 1592-1598. https://doi.org/10.1038/nn.4394

© 2016 Nature America, Inc., part of Springer Nature. All rights reserved. During nervous system development, neurons extend axons along well-defined pathways. The current understanding of axon pathfinding is based mainly on chemical signaling. Howev... Read More about Mechanosensing is critical for axon growth in the developing brain.

Lysophosphatidic acid receptors (LPARs): Potential targets for the treatment of neuropathic pain (2016)
Journal Article
Velasco, M., O'Sullivan, C., & Sheridan, G. K. (2017). Lysophosphatidic acid receptors (LPARs): Potential targets for the treatment of neuropathic pain. Neuropharmacology, 113, 608-617. https://doi.org/10.1016/j.neuropharm.2016.04.002

Neuropathic pain can arise from lesions to peripheral or central nerve fibres leading to spontaneous action potential generation and a lowering of the nociceptive threshold. Clinically, neuropathic pain can manifest in many chronic disease states suc... Read More about Lysophosphatidic acid receptors (LPARs): Potential targets for the treatment of neuropathic pain.