Nonyloxytryptamine mimics polysialic acid and modulates neuronal and glial functions in cell culture

Gabriele Loers, Vedangana Saini, Bibhudatta Mishra, Florentia Papastefanaki, David Lutz, Sidhartha Chaudhury, Daniel R. Ripoll, Anders Wallqvist, Sheraz Gul, Melitta Camartin, Gurcharan Kaur

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Polysialic acid (PSA) is a major regulator of cell-cell interactions in the developing nervous system and in neural plasticity in the adult. As a polyanionic molecule with high water-binding capacity, PSA increases the intercellular space generating permissive conditions for cell motility. PSA enhances stem cell migration and axon path finding and promotes repair in the lesioned peripheral and central nervous systems, thus contributing to regeneration. As a next step in developing an improved PSA-based approach to treat nervous system injuries, we searched for small organic compounds that mimic PSA and identified as a PSA mimetic 5-nonyloxytryptamine oxalate, described as a selective 5-hydroxytryptamine receptor 1B (5-HT1B) agonist. Similar to PSA, 5-nonyloxytryptamine binds to the PSA-specific monoclonal antibody 735, enhances neurite outgrowth of cultured primary neurons and process formation of Schwann cells, protects neurons from oxidative stress, reduces migration of astrocytes and enhances myelination in vitro. Furthermore, nonyloxytryptamine treatment enhances expression of the neural cell adhesion molecule (NCAM) and its polysialylated form PSA-NCAM and reduces expression of the microtubule-associated protein MAP2 in cultured neuroblastoma cells. These results demonstrate that 5-nonyloxytryptamine mimics PSA and triggers PSA-mediated functions, thus contributing to the repertoire of molecules with the potential to improve recovery in acute and chronic injuries of the mammalian peripheral and central nervous systems. Polysialic acid (PSA) plays important roles in nervous system development, as well as synaptic plasticity and regeneration in the adult. 5-Nonyloxytryptamine oxalate (5-NOT) mimics PSA and triggers PSA-mediated functions in neurons and glial cells. 5-NOT stimulates neuritogenesis, myelination and Schwann cell migration. This study sets the basis to develop a PSA-mediated therapy of acute and chronic nervous system diseases. Polysialic acid (PSA) plays important roles in nervous system development, as well as synaptic plasticity and regeneration in the adult. 5-Nonyloxytryptamine oxalate (5-NOT) mimics PSA and triggers PSA-mediated functions in neurons and glial cells. 5-NOT stimulates neuritogenesis, myelination and Schwann cell migration. This study sets the basis to develop a PSA-mediated therapy of acute and chronic nervous system diseases.

Original languageEnglish (US)
Pages (from-to)88-100
Number of pages13
JournalJournal of neurochemistry
Volume128
Issue number1
DOIs
StatePublished - Jan 1 2014

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Cell culture
Neuroglia
Cell Culture Techniques
Neurology
Oxalates
Neurons
Neuronal Plasticity
Cell Movement
Schwann Cells
Nervous System
polysialic acid
Plasticity
Regeneration
Neural Cell Adhesion Molecules
Cells
Peripheral Nervous System
Nervous System Diseases
Central Nervous System
Receptor, Serotonin, 5-HT1B
Nervous System Trauma

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

Keywords

  • 5-nonyloxytryptamine oxalate
  • migration
  • neural cell adhesion molecule
  • neurite outgrowth
  • polysialic acid
  • scratch injury

Cite this

Loers, G., Saini, V., Mishra, B., Papastefanaki, F., Lutz, D., Chaudhury, S., ... Kaur, G. (2014). Nonyloxytryptamine mimics polysialic acid and modulates neuronal and glial functions in cell culture. Journal of neurochemistry, 128(1), 88-100. https://doi.org/10.1111/jnc.12408
Loers, Gabriele ; Saini, Vedangana ; Mishra, Bibhudatta ; Papastefanaki, Florentia ; Lutz, David ; Chaudhury, Sidhartha ; Ripoll, Daniel R. ; Wallqvist, Anders ; Gul, Sheraz ; Camartin, Melitta ; Kaur, Gurcharan. / Nonyloxytryptamine mimics polysialic acid and modulates neuronal and glial functions in cell culture. In: Journal of neurochemistry. 2014 ; Vol. 128, No. 1. pp. 88-100.
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Loers, G, Saini, V, Mishra, B, Papastefanaki, F, Lutz, D, Chaudhury, S, Ripoll, DR, Wallqvist, A, Gul, S, Camartin, M & Kaur, G 2014, 'Nonyloxytryptamine mimics polysialic acid and modulates neuronal and glial functions in cell culture', Journal of neurochemistry, vol. 128, no. 1, pp. 88-100. https://doi.org/10.1111/jnc.12408

Nonyloxytryptamine mimics polysialic acid and modulates neuronal and glial functions in cell culture. / Loers, Gabriele; Saini, Vedangana; Mishra, Bibhudatta; Papastefanaki, Florentia; Lutz, David; Chaudhury, Sidhartha; Ripoll, Daniel R.; Wallqvist, Anders; Gul, Sheraz; Camartin, Melitta; Kaur, Gurcharan.

In: Journal of neurochemistry, Vol. 128, No. 1, 01.01.2014, p. 88-100.

Research output: Contribution to journalArticle

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T1 - Nonyloxytryptamine mimics polysialic acid and modulates neuronal and glial functions in cell culture

AU - Loers, Gabriele

AU - Saini, Vedangana

AU - Mishra, Bibhudatta

AU - Papastefanaki, Florentia

AU - Lutz, David

AU - Chaudhury, Sidhartha

AU - Ripoll, Daniel R.

AU - Wallqvist, Anders

AU - Gul, Sheraz

AU - Camartin, Melitta

AU - Kaur, Gurcharan

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N2 - Polysialic acid (PSA) is a major regulator of cell-cell interactions in the developing nervous system and in neural plasticity in the adult. As a polyanionic molecule with high water-binding capacity, PSA increases the intercellular space generating permissive conditions for cell motility. PSA enhances stem cell migration and axon path finding and promotes repair in the lesioned peripheral and central nervous systems, thus contributing to regeneration. As a next step in developing an improved PSA-based approach to treat nervous system injuries, we searched for small organic compounds that mimic PSA and identified as a PSA mimetic 5-nonyloxytryptamine oxalate, described as a selective 5-hydroxytryptamine receptor 1B (5-HT1B) agonist. Similar to PSA, 5-nonyloxytryptamine binds to the PSA-specific monoclonal antibody 735, enhances neurite outgrowth of cultured primary neurons and process formation of Schwann cells, protects neurons from oxidative stress, reduces migration of astrocytes and enhances myelination in vitro. Furthermore, nonyloxytryptamine treatment enhances expression of the neural cell adhesion molecule (NCAM) and its polysialylated form PSA-NCAM and reduces expression of the microtubule-associated protein MAP2 in cultured neuroblastoma cells. These results demonstrate that 5-nonyloxytryptamine mimics PSA and triggers PSA-mediated functions, thus contributing to the repertoire of molecules with the potential to improve recovery in acute and chronic injuries of the mammalian peripheral and central nervous systems. Polysialic acid (PSA) plays important roles in nervous system development, as well as synaptic plasticity and regeneration in the adult. 5-Nonyloxytryptamine oxalate (5-NOT) mimics PSA and triggers PSA-mediated functions in neurons and glial cells. 5-NOT stimulates neuritogenesis, myelination and Schwann cell migration. This study sets the basis to develop a PSA-mediated therapy of acute and chronic nervous system diseases. Polysialic acid (PSA) plays important roles in nervous system development, as well as synaptic plasticity and regeneration in the adult. 5-Nonyloxytryptamine oxalate (5-NOT) mimics PSA and triggers PSA-mediated functions in neurons and glial cells. 5-NOT stimulates neuritogenesis, myelination and Schwann cell migration. This study sets the basis to develop a PSA-mediated therapy of acute and chronic nervous system diseases.

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KW - 5-nonyloxytryptamine oxalate

KW - migration

KW - neural cell adhesion molecule

KW - neurite outgrowth

KW - polysialic acid

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