Endothelin-1 modulates anterograde fast axonal transport in the central nervous system

Martha E. Stokely, Thomas Yorio, Michael A. King

Research output: Contribution to journalArticleResearchpeer-review

28 Citations (Scopus)

Abstract

Anterograde fast axonal transport (FAxT) maintains synaptic function and provides materials necessary for neuronal survival. Localized changes in FAxT are associated with a variety of central nervous system (CNS) neuropathies, where they may contribute to inappropriate remodeling, a process more appropriately involved in synaptic plasticity and development. In some cases, developmental remodeling is regulated by localized secretion of endothelins (ETs), neuroinflammatory peptides that are also pathologically elevated in cases of neurologic disease, CNS injury, or ischemia. To investigate the potential role of ETs in these processes, we decided to test whether locally elevated endothelin-1 (ET-1) modulates FAxT in adult CNS tissues. We used the established in vivo rat optic nerve model and a novel ex vivo rat hippocampal slice model to test this hypothesis. In vivo, exogenously elevated vitreal ET-1 significantly affected protein composition of FAxT-cargos as well as the abundance and peak delivery times for metabolically-labeled proteins that were transported into the optic nerve. Proteins with molecular weights of 139, 118, 89, 80, 64, 59, 51, 45, 42, 37, and 25 kDa were evaluated at injection-sacrifice intervals (ISIs) of 24, 28, 32, and 36 hr. In acute hippocampal slices maintained on nonvascular supplies of glucose and oxygen, ET-1 significantly decreased the distance traveled along the Schaffer collateral tract by nonmetabolically-labeled lipid rafts at 5 and 10 min after pulse-labeling. In both models, ET-1 significantly affected transport or targeted delivery of FaxT-cargos, suggesting that ET-1 has the potential to modulate FAxT in adult CNS tissues.

Original languageEnglish
Pages (from-to)598-607
Number of pages10
JournalJournal of Neuroscience Research
Volume79
Issue number5
DOIs
StatePublished - 1 Mar 2005

Fingerprint

Axonal Transport
Endothelin-1
Central Nervous System
Nerve Tissue
Endothelins
Optic Nerve
Nervous System Trauma
Proteins
Neuronal Plasticity
Nervous System Diseases
Hippocampus
Ischemia
Molecular Weight
Oxygen
Lipids
Glucose
Peptides
Injections

Keywords

  • Endothelin
  • Fast axonal transport
  • Hippocampus
  • Lipid rafts
  • Optic nerve

Cite this

@article{44b83b0627fa4f07960715ffc7f38cac,
title = "Endothelin-1 modulates anterograde fast axonal transport in the central nervous system",
abstract = "Anterograde fast axonal transport (FAxT) maintains synaptic function and provides materials necessary for neuronal survival. Localized changes in FAxT are associated with a variety of central nervous system (CNS) neuropathies, where they may contribute to inappropriate remodeling, a process more appropriately involved in synaptic plasticity and development. In some cases, developmental remodeling is regulated by localized secretion of endothelins (ETs), neuroinflammatory peptides that are also pathologically elevated in cases of neurologic disease, CNS injury, or ischemia. To investigate the potential role of ETs in these processes, we decided to test whether locally elevated endothelin-1 (ET-1) modulates FAxT in adult CNS tissues. We used the established in vivo rat optic nerve model and a novel ex vivo rat hippocampal slice model to test this hypothesis. In vivo, exogenously elevated vitreal ET-1 significantly affected protein composition of FAxT-cargos as well as the abundance and peak delivery times for metabolically-labeled proteins that were transported into the optic nerve. Proteins with molecular weights of 139, 118, 89, 80, 64, 59, 51, 45, 42, 37, and 25 kDa were evaluated at injection-sacrifice intervals (ISIs) of 24, 28, 32, and 36 hr. In acute hippocampal slices maintained on nonvascular supplies of glucose and oxygen, ET-1 significantly decreased the distance traveled along the Schaffer collateral tract by nonmetabolically-labeled lipid rafts at 5 and 10 min after pulse-labeling. In both models, ET-1 significantly affected transport or targeted delivery of FaxT-cargos, suggesting that ET-1 has the potential to modulate FAxT in adult CNS tissues.",
keywords = "Endothelin, Fast axonal transport, Hippocampus, Lipid rafts, Optic nerve",
author = "Stokely, {Martha E.} and Thomas Yorio and King, {Michael A.}",
year = "2005",
month = "3",
day = "1",
doi = "10.1002/jnr.20383",
language = "English",
volume = "79",
pages = "598--607",
journal = "Journal of Neuroscience Research",
issn = "0360-4012",
publisher = "Wiley-Liss Inc.",
number = "5",

}

Endothelin-1 modulates anterograde fast axonal transport in the central nervous system. / Stokely, Martha E.; Yorio, Thomas; King, Michael A.

In: Journal of Neuroscience Research, Vol. 79, No. 5, 01.03.2005, p. 598-607.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Endothelin-1 modulates anterograde fast axonal transport in the central nervous system

AU - Stokely, Martha E.

AU - Yorio, Thomas

AU - King, Michael A.

PY - 2005/3/1

Y1 - 2005/3/1

N2 - Anterograde fast axonal transport (FAxT) maintains synaptic function and provides materials necessary for neuronal survival. Localized changes in FAxT are associated with a variety of central nervous system (CNS) neuropathies, where they may contribute to inappropriate remodeling, a process more appropriately involved in synaptic plasticity and development. In some cases, developmental remodeling is regulated by localized secretion of endothelins (ETs), neuroinflammatory peptides that are also pathologically elevated in cases of neurologic disease, CNS injury, or ischemia. To investigate the potential role of ETs in these processes, we decided to test whether locally elevated endothelin-1 (ET-1) modulates FAxT in adult CNS tissues. We used the established in vivo rat optic nerve model and a novel ex vivo rat hippocampal slice model to test this hypothesis. In vivo, exogenously elevated vitreal ET-1 significantly affected protein composition of FAxT-cargos as well as the abundance and peak delivery times for metabolically-labeled proteins that were transported into the optic nerve. Proteins with molecular weights of 139, 118, 89, 80, 64, 59, 51, 45, 42, 37, and 25 kDa were evaluated at injection-sacrifice intervals (ISIs) of 24, 28, 32, and 36 hr. In acute hippocampal slices maintained on nonvascular supplies of glucose and oxygen, ET-1 significantly decreased the distance traveled along the Schaffer collateral tract by nonmetabolically-labeled lipid rafts at 5 and 10 min after pulse-labeling. In both models, ET-1 significantly affected transport or targeted delivery of FaxT-cargos, suggesting that ET-1 has the potential to modulate FAxT in adult CNS tissues.

AB - Anterograde fast axonal transport (FAxT) maintains synaptic function and provides materials necessary for neuronal survival. Localized changes in FAxT are associated with a variety of central nervous system (CNS) neuropathies, where they may contribute to inappropriate remodeling, a process more appropriately involved in synaptic plasticity and development. In some cases, developmental remodeling is regulated by localized secretion of endothelins (ETs), neuroinflammatory peptides that are also pathologically elevated in cases of neurologic disease, CNS injury, or ischemia. To investigate the potential role of ETs in these processes, we decided to test whether locally elevated endothelin-1 (ET-1) modulates FAxT in adult CNS tissues. We used the established in vivo rat optic nerve model and a novel ex vivo rat hippocampal slice model to test this hypothesis. In vivo, exogenously elevated vitreal ET-1 significantly affected protein composition of FAxT-cargos as well as the abundance and peak delivery times for metabolically-labeled proteins that were transported into the optic nerve. Proteins with molecular weights of 139, 118, 89, 80, 64, 59, 51, 45, 42, 37, and 25 kDa were evaluated at injection-sacrifice intervals (ISIs) of 24, 28, 32, and 36 hr. In acute hippocampal slices maintained on nonvascular supplies of glucose and oxygen, ET-1 significantly decreased the distance traveled along the Schaffer collateral tract by nonmetabolically-labeled lipid rafts at 5 and 10 min after pulse-labeling. In both models, ET-1 significantly affected transport or targeted delivery of FaxT-cargos, suggesting that ET-1 has the potential to modulate FAxT in adult CNS tissues.

KW - Endothelin

KW - Fast axonal transport

KW - Hippocampus

KW - Lipid rafts

KW - Optic nerve

UR - http://www.scopus.com/inward/record.url?scp=16444367915&partnerID=8YFLogxK

U2 - 10.1002/jnr.20383

DO - 10.1002/jnr.20383

M3 - Article

VL - 79

SP - 598

EP - 607

JO - Journal of Neuroscience Research

JF - Journal of Neuroscience Research

SN - 0360-4012

IS - 5

ER -