Neurite formation by neurons derived from adult rat hippocampal progenitor cells is susceptible to myelin inhibition

Carla B Mellough, Seongeun Cho, Andrew Wood, Stefan Przyborski

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Myelin-associated inhibitors expressed following injury to the adult central nervous system (CNS) induce growth cone collapse and retraction of the axonal cytoskeleton. Myelin-associated glycoprotein (MAG) is a bi-functional molecule that promotes neuritogenesis in some immature neurons during development then becomes inhibitory to neurite outgrowth as neurons mature. Progress is being made towards the elucidation of the downstream events that regulate myelin inhibition of regeneration in neuronal populations. However it is not known how adult-derived neural stem cells or progenitors respond to myelin during neuronal differentiation and neuritogenesis. Here we examine the effect of MAG on neurons derived from an adult rat hippocampal progenitor cell line (AHPCs). We show that, unlike their developmental counterparts, AHPC-derived neurons are susceptible to MAG inhibition of neuritogenesis during differentiation and display a 57% reduction in neurite outgrowth when compared with controls. We demonstrate that this effect can be overcome (by up to 69%) by activation of the neurotrophin, cyclic AMP and protein kinase A pathways or by Rho-kinase suppression. We also demonstrate that combination of these factors enhanced neurite outgrowth from differentiating neurons in the presence of MAG. This work provides important information for the successful generation of new neurons from adult neural stem cell populations within compromised adult circuitry and is thus directly relevant to endogenous repair and regeneration of the adult CNS.

Original languageEnglish
Pages (from-to)333-340
Number of pages8
JournalNeurochemistry International
Volume59
Issue number3
DOIs
Publication statusPublished - Sep 2011
Externally publishedYes

Fingerprint

Neurites
Myelin Sheath
Myelin-Associated Glycoprotein
Stem Cells
Neurons
Neural Stem Cells
Nerve Growth Factors
Regeneration
Central Nervous System
Adenylate Kinase
rho-Associated Kinases
Growth Cones
Adult Stem Cells
Cyclic AMP-Dependent Protein Kinases
Cytoskeleton
Cyclic AMP
Population
Cell Line
Wounds and Injuries

Cite this

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title = "Neurite formation by neurons derived from adult rat hippocampal progenitor cells is susceptible to myelin inhibition",
abstract = "Myelin-associated inhibitors expressed following injury to the adult central nervous system (CNS) induce growth cone collapse and retraction of the axonal cytoskeleton. Myelin-associated glycoprotein (MAG) is a bi-functional molecule that promotes neuritogenesis in some immature neurons during development then becomes inhibitory to neurite outgrowth as neurons mature. Progress is being made towards the elucidation of the downstream events that regulate myelin inhibition of regeneration in neuronal populations. However it is not known how adult-derived neural stem cells or progenitors respond to myelin during neuronal differentiation and neuritogenesis. Here we examine the effect of MAG on neurons derived from an adult rat hippocampal progenitor cell line (AHPCs). We show that, unlike their developmental counterparts, AHPC-derived neurons are susceptible to MAG inhibition of neuritogenesis during differentiation and display a 57{\%} reduction in neurite outgrowth when compared with controls. We demonstrate that this effect can be overcome (by up to 69{\%}) by activation of the neurotrophin, cyclic AMP and protein kinase A pathways or by Rho-kinase suppression. We also demonstrate that combination of these factors enhanced neurite outgrowth from differentiating neurons in the presence of MAG. This work provides important information for the successful generation of new neurons from adult neural stem cell populations within compromised adult circuitry and is thus directly relevant to endogenous repair and regeneration of the adult CNS.",
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Neurite formation by neurons derived from adult rat hippocampal progenitor cells is susceptible to myelin inhibition. / Mellough, Carla B; Cho, Seongeun; Wood, Andrew; Przyborski, Stefan.

In: Neurochemistry International, Vol. 59, No. 3, 09.2011, p. 333-340.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Neurite formation by neurons derived from adult rat hippocampal progenitor cells is susceptible to myelin inhibition

AU - Mellough, Carla B

AU - Cho, Seongeun

AU - Wood, Andrew

AU - Przyborski, Stefan

N1 - Copyright © 2011 Elsevier Ltd. All rights reserved.

PY - 2011/9

Y1 - 2011/9

N2 - Myelin-associated inhibitors expressed following injury to the adult central nervous system (CNS) induce growth cone collapse and retraction of the axonal cytoskeleton. Myelin-associated glycoprotein (MAG) is a bi-functional molecule that promotes neuritogenesis in some immature neurons during development then becomes inhibitory to neurite outgrowth as neurons mature. Progress is being made towards the elucidation of the downstream events that regulate myelin inhibition of regeneration in neuronal populations. However it is not known how adult-derived neural stem cells or progenitors respond to myelin during neuronal differentiation and neuritogenesis. Here we examine the effect of MAG on neurons derived from an adult rat hippocampal progenitor cell line (AHPCs). We show that, unlike their developmental counterparts, AHPC-derived neurons are susceptible to MAG inhibition of neuritogenesis during differentiation and display a 57% reduction in neurite outgrowth when compared with controls. We demonstrate that this effect can be overcome (by up to 69%) by activation of the neurotrophin, cyclic AMP and protein kinase A pathways or by Rho-kinase suppression. We also demonstrate that combination of these factors enhanced neurite outgrowth from differentiating neurons in the presence of MAG. This work provides important information for the successful generation of new neurons from adult neural stem cell populations within compromised adult circuitry and is thus directly relevant to endogenous repair and regeneration of the adult CNS.

AB - Myelin-associated inhibitors expressed following injury to the adult central nervous system (CNS) induce growth cone collapse and retraction of the axonal cytoskeleton. Myelin-associated glycoprotein (MAG) is a bi-functional molecule that promotes neuritogenesis in some immature neurons during development then becomes inhibitory to neurite outgrowth as neurons mature. Progress is being made towards the elucidation of the downstream events that regulate myelin inhibition of regeneration in neuronal populations. However it is not known how adult-derived neural stem cells or progenitors respond to myelin during neuronal differentiation and neuritogenesis. Here we examine the effect of MAG on neurons derived from an adult rat hippocampal progenitor cell line (AHPCs). We show that, unlike their developmental counterparts, AHPC-derived neurons are susceptible to MAG inhibition of neuritogenesis during differentiation and display a 57% reduction in neurite outgrowth when compared with controls. We demonstrate that this effect can be overcome (by up to 69%) by activation of the neurotrophin, cyclic AMP and protein kinase A pathways or by Rho-kinase suppression. We also demonstrate that combination of these factors enhanced neurite outgrowth from differentiating neurons in the presence of MAG. This work provides important information for the successful generation of new neurons from adult neural stem cell populations within compromised adult circuitry and is thus directly relevant to endogenous repair and regeneration of the adult CNS.

KW - Animals

KW - Cell Proliferation

KW - Cells, Cultured

KW - Hippocampus

KW - Myelin Sheath

KW - Neurites

KW - Rats

KW - Stem Cells

KW - Journal Article

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