Reassembly of the axon initial segment and nodes of Ranvier in regenerated axons of the central nervous system

The axon initial segment (AIS), the domain responsible for action potential initiation and maintenance of neuronal polarity, is targeted for disruption in a variety of central nervous system pathological insults. Previous work in our laboratory implicates oxidative stress as a potential mediator of structural AIS alterations in two separate mouse models of central nervous system inflammation, as these effects were attenuated following reactive oxygen species scavenging and NADPH oxidase-2 ablation. While these studies suggest a role for oxidative stress in modulation of the AIS, the direct effects of reactive oxygen and nitrogen species (ROS/RNS) on the stability of this domain remain unclear. Here, we demonstrate that oxidative stress, as induced through treatment with 3-morpholinosydnonimine (SIN-1), a spontaneous ROS/RNS generator, drives a reversible loss of AIS protein clustering in primary cortical neurons in vitro. Pharmacological inhibition of both voltage-dependent and intracellular calcium (Ca2+) channels suggests that this mechanism of AIS disruption involves Ca2+ entry specifically through L-type voltage-dependent Ca2+ channels and its release from IP3-gated intracellular stores. Furthermore, ROS/RNS-induced AIS disruption is dependent upon activation of calpain, a Ca2+-activated protease previously shown to drive AIS modulation. Overall, we demonstrate for the first time that oxidative stress, as induced through exogenously applied ROS/RNS, is capable of driving structural alterations in the AIS complex.

Download Full-text

The Structure and Conduction Velocity of the Medullated Nerve Fibres of Prawns

Journal of Experimental Biology ◽

10.1242/jeb.18.1.50 ◽

1941 ◽

Vol 18 (1) ◽

pp. 50-54 ◽

Cited By ~ 1

Author(s):

W. HOLMES ◽

R. J. PUMPHREY ◽

J. Z. YOUNG

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Conduction Velocity ◽

Myelin Sheath ◽

Axon Diameter ◽

Relative Thickness ◽

Nodes Of Ranvier ◽

Nerve Fibres ◽

The Central Nervous System ◽

Myelinated Fibres

1. The structure of the myelinated fibres of prawns is described, and the homologies of the nucleated sheath which lies between the axon and the fatty layer discussed. 2. The relative thickness of the myelin sheath increases with decrease in total diameter of the fibre along a curve similar in shape to that found in vertebrates and earthworms. 3. Nodes of Ranvier are found in the sheaths of most fibres of a diameter greater than about 13µ 4. The nodes are similar to those in vertebrate nerves in that the myelin sheath is interrupted at the node. 5. The conduction velocity of fibres in the central nervous system of axon diameter 26µ and total diameter 35µ is between 18 and 23 m. per sec., a rate faster than is found in the "unmyelinated" fibres of similar size in other crustacea.

Download Full-text

Nodes of ranvier in the central nervous system

The Journal of Comparative Neurology ◽

10.1002/cne.901030103 ◽

1955 ◽

Vol 103 (1) ◽

pp. 11-15 ◽

Cited By ~ 11

Author(s):

Daniel C. Pease

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Nodes Of Ranvier ◽

The Central Nervous System

Download Full-text

Glial and neuronal isoforms of Neurofascin have distinct roles in the assembly of nodes of Ranvier in the central nervous system

The Journal of Cell Biology ◽

10.1083/jcb.200712154 ◽

2008 ◽

Vol 181 (7) ◽

pp. 1169-1177 ◽

Cited By ~ 120

Author(s):

Barbara Zonta ◽

Steven Tait ◽

Shona Melrose ◽

Heather Anderson ◽

Sheila Harroch ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Sodium Channels ◽

Molecular Mechanisms ◽

Nerve Impulse ◽

Node Of Ranvier ◽

Nodes Of Ranvier ◽

Additional Function ◽

The Central Nervous System ◽

Adhesion Complex

Rapid nerve impulse conduction in myelinated axons requires the concentration of voltage-gated sodium channels at nodes of Ranvier. Myelin-forming oligodendrocytes in the central nervous system (CNS) induce the clustering of sodium channels into nodal complexes flanked by paranodal axoglial junctions. However, the molecular mechanisms for nodal complex assembly in the CNS are unknown. Two isoforms of Neurofascin, neuronal Nfasc186 and glial Nfasc155, are components of the nodal and paranodal complexes, respectively. Neurofascin-null mice have disrupted nodal and paranodal complexes. We show that transgenic Nfasc186 can rescue the nodal complex when expressed in Nfasc−/− mice in the absence of the Nfasc155–Caspr–Contactin adhesion complex. Reconstitution of the axoglial adhesion complex by expressing transgenic Nfasc155 in oligodendrocytes also rescues the nodal complex independently of Nfasc186. Furthermore, the Nfasc155 adhesion complex has an additional function in promoting the migration of myelinating processes along CNS axons. We propose that glial and neuronal Neurofascins have distinct functions in the assembly of the CNS node of Ranvier.

Download Full-text

Multiple myelinated branches from nodes of Ranvier in the central nervous system

Brain Research ◽

10.1016/0006-8993(72)90329-0 ◽

1972 ◽

Vol 44 (2) ◽

pp. 652-655 ◽

Cited By ~ 13

Author(s):

A.R. Lieberman ◽

K.E. Webster ◽

J. S˛pac˛ek

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Nodes Of Ranvier ◽

The Central Nervous System

Download Full-text

The Axonal Cytoskeleton and the Assembly of Nodes of Ranvier

The Neuroscientist ◽

10.1177/1073858417710897 ◽

2017 ◽

Vol 24 (2) ◽

pp. 104-110 ◽

Cited By ~ 13

Author(s):

Aniket Ghosh ◽

Diane L. Sherman ◽

Peter J. Brophy

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Protein Complexes ◽

Nerve Impulse ◽

Nodes Of Ranvier ◽

Axonal Membrane ◽

Voltage Gated Sodium Channels ◽

The Central Nervous System ◽

High Concentrations ◽

Surface Domains

Vertebrate nervous systems rely on rapid nerve impulse transmission to support their complex functions. Fast conduction depends on ensheathment of nerve axons by myelin-forming glia and the clustering of high concentrations of voltage-gated sodium channels (Nav) in the axonal gaps between myelinated segments. These gaps are the nodes of Ranvier. Depolarization of the axonal membrane initiates the action potential responsible for impulse transmission, and the Nav help ensure that this is restricted to nodes. In the central nervous system, the formation of nodes and the clustering of Nav in nodal complexes is achieved when oligodendrocytes extend their processes and ultimately ensheath axons with myelin. However, the mechanistic relationship between myelination and the formation of nodal complexes is unclear. Here we review recent work in the central nervous system that shows that axons, by assembling distinct cytoskeletal interfaces, are not only active participants in oligodendrocyte process migration but are also significant contributors to the mechanisms by which myelination causes Nav clustering. We also discuss how the segregation of membrane protein complexes through their interaction with distinct cytoskeletal complexes may play a wider role in establishing surface domains in axons.

Download Full-text