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Axon diameter and axonal transport: In vivo and in vitro effects of androgens

Published on Jul 1, 2015in NeuroImage5.81
· DOI :10.1016/j.neuroimage.2015.04.048
M. Pesaresi2
Estimated H-index: 2
(U of T: University of Toronto),
R. Soon-Shiong1
Estimated H-index: 1
(U of T: University of Toronto)
+ 3 AuthorsTomáš Paus82
Estimated H-index: 82
(U of T: University of Toronto)
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Abstract
Abstract Testosterone is a sex hormone involved in brain maturation via multiple molecular mechanisms. Previous human studies described age-related changes in the overall volume and structural properties of white matter during male puberty. Based on this work, we have proposed that testosterone may induce a radial growth of the axon and, possibly, modulate axonal transport. In order to determine whether this is the case we have used two different experimental approaches. With electron microscopy, we have evaluated sex differences in the structural properties of axons in the corpus callosum (splenium) of young rats, and tested consequences of castration carried out after weaning. Then we examined in vitro the effect of the non-aromatizable androgen Mibolerone on the structure and bidirectional transport of wheat-germ agglutinin vesicles in the axons of cultured sympathetic neurons. With electron microscopy, we found robust sex differences in axonal diameter (males > females) and g ratio (males > females). Removal of endogenous testosterone by castration was associated with lower axon diameter and lower g ratio in castrated (vs. intact) males. In vitro , Mibolerone influenced the axonal transport in a time- and dose-dependent manner, and increased the axon caliber as compared with vehicle-treated neurons. These findings are consistent with the role of testosterone in shaping the axon by regulating its radial growth, as predicted by the initial human studies.
  • References (99)
  • Citations (24)
Cite
References99
Newest
Published on Sep 1, 2014in Neuroscience3.24
Tomáš Paus82
Estimated H-index: 82
(U of T: University of Toronto),
M. Pesaresi2
Estimated H-index: 2
(U of T: University of Toronto),
Leon French14
Estimated H-index: 14
(U of T: University of Toronto)
Abstract There are two ways to picture white matter: as a grid of electrical wires or a network of roads. The first metaphor captures the classical function of an axon as conductor of action potentials (and information) from one brain region to another. The second one points to the important role of axons in a bi-directional transport of biological molecules and organelles between the cell body and synapse. Given the wide variety of such cargoes, a well-functioning axonal transport is critical f...
Published on Sep 4, 2013in The Journal of Neuroscience6.07
Roberto Caminiti38
Estimated H-index: 38
,
Filippo Carducci36
Estimated H-index: 36
+ 5 AuthorsGiorgio M. Innocenti42
Estimated H-index: 42
(KI: Karolinska Institutet)
Three macaque monkeys and 13 healthy human volunteers underwent diffusion tensor MRI with a 3 Tesla scanner for diffusion tract tracing (DTT) reconstruction of callosal bundles from different areas. In six macaque monkeys and three human subjects, the length of fiber tracts was obtained from histological data and combined with information on the distribution of axon diameter, so as to estimate callosal conduction delays from different areas. The results showed that in monkeys, the spectrum of tr...
Published on Jan 28, 2013in PLOS ONE2.78
S. Pajevic21
Estimated H-index: 21
(CIT: Center for Information Technology),
Peter J. Basser58
Estimated H-index: 58
(NIH: National Institutes of Health)
Many important functional properties affecting nerve conduction are influenced by axon diameter. It is also known that the axon diameter distribution (ADD) in normal nerve fascicles is heterogeneous and skewed. A recent attempt to model and explain the parametric form of these distributions was based on biomechanical principles. Here we explore a neurophysiologically-based hypothesis that the observed ADD can be obtained by optimizing the information flow through a fascicle subject to reasonable...
Published on Jan 1, 2013in Brain11.81
Rashad Hussain4
Estimated H-index: 4
(UDS: University of Strasbourg),
Abdel M. Ghoumari15
Estimated H-index: 15
(University of Paris-Sud)
+ 11 AuthorsSakina Mhaouty-Kodja10
Estimated H-index: 10
(UPMC: Pierre-and-Marie-Curie University)
Myelin regeneration is a major therapeutic goal in demyelinating diseases, and the failure to remyelinate rapidly has profound consequences for the health of axons and for brain function. However, there is no efficient treatment for stimulating myelin repair, and current therapies are limited to anti-inflammatory agents. Males are less likely to develop multiple sclerosis than females, but often have a more severe disease course and reach disability milestones at an earlier age than females, and...
Published on Nov 2, 2012in Science41.04
Nathan D. Derr4
Estimated H-index: 4
(Harvard University),
Brian S. Goodman5
Estimated H-index: 5
(Harvard University)
+ 3 AuthorsSamara L. Reck-Peterson25
Estimated H-index: 25
(Harvard University)
In eukaryotic cells, nearly all long-distance transport of cargos is carried out by the microtubule-based motors kinesin and dynein. These opposite-polarity motors move cargos bidirectionally so that they reach their cellular destinations with spatial and temporal specificity. To understand transport by motor ensembles, Derr et al. (p. [662][1], published online 11 October; see the Persective by [Diehl][2] ) used a DNA scaffold for building an artificial cargo that could be programmed to bind di...
Published on Sep 1, 2012in Cerebral Cortex5.44
Megan M. Herting19
Estimated H-index: 19
(OHSU: Oregon Health & Science University),
Emily C. Maxwell2
Estimated H-index: 2
(OHSU: Oregon Health & Science University)
+ 1 AuthorsBonnie J. Nagel33
Estimated H-index: 33
(OHSU: Oregon Health & Science University)
Background: During adolescence, numerous factors influence the organization of the brain. It is unclear what influence sex and puberty have on white matter microstructure, as well as the role that rapidly increasing sex steroids play. Methods: White matter microstructure was examined in 77 adolescents (ages 10–16) using diffusion tensor imaging. Multiple regression analyses were performed to examine the relationships between fractional anisotropy (FA) and mean diffusivity (MD) and sex, puberty, ...
Published on Jul 15, 2012in Journal of Cell Science4.52
Aidong Yuan15
Estimated H-index: 15
(NYU: New York University),
Mala V. Rao18
Estimated H-index: 18
(NYU: New York University)
+ 1 AuthorsRalph A. Nixon72
Estimated H-index: 72
(NYU: New York University)
Neurofilaments (NFs) are intermediate filaments with a diameter of 10 nm, similar to that of neurons. Although they are present in perikarya and dendrites, neurofilaments are particularly abundant in axons, where they are essential for the radial growth of axons during development, the maintenance
Published on Jun 1, 2012in Cerebral Cortex5.44
Simone Tomasi11
Estimated H-index: 11
(UNITO: University of Turin),
Roberto Caminiti38
Estimated H-index: 38
(Sapienza University of Rome),
Giorgio M. Innocenti42
Estimated H-index: 42
(KI: Karolinska Institutet)
Cortical areas differ in the size and distribution of neuronal cellbodies, density, and distribution of myelinated axons, connections,andfunctional properties.Wefindthattheyalsodiffer inthediameterof long corticofugal axons, with the thickest axons originating fromprimary motor, somatosensory, and visual areas and the thinnestones from prefrontal and temporal areas. Since diameter isproportional to axonal conduction velocity, it can be inferred thataction potentials issued from the different area...
Published on May 1, 2012in Molecular Biology of the Cell3.90
Gerald F. Reis2
Estimated H-index: 2
(UCSD: University of California, San Diego),
Ge Yang21
Estimated H-index: 21
(CMU: Carnegie Mellon University)
+ 6 AuthorsLawrence S.B. Goldstein66
Estimated H-index: 66
(UCSD: University of California, San Diego)
Bidirectional axonal transport driven by kinesin and dynein along microtubules is critical to neuronal viability and function. To evaluate axonal transport mechanisms, we developed a high-resolution imaging system to track the movement of amyloid precursor protein (APP) vesicles in Drosophila segmental nerve axons. Computational analyses of a large number of moving vesicles in defined genetic backgrounds with partial reduction or overexpression of motor proteins enabled us to test with high prec...
Published on Jan 11, 2012in The Journal of Neuroscience6.07
János A. Perge10
Estimated H-index: 10
,
Jeremy E. Niven22
Estimated H-index: 22
+ 2 AuthorsPeter Sterling64
Estimated H-index: 64
CNS axons differ in diameter (d) by nearly 100-fold (∼0.1-10 μm); therefore, they differ in cross-sectional area (d(2)) and volume by nearly 10,000-fold. If, as found for optic nerve, mitochondrial volume fraction is constant with axon diameter, energy capacity would rise with axon volume, also as d(2). We asked, given constraints on space and energy, what functional requirements set an axon's diameter? Surveying 16 fiber groups spanning nearly the full range of diameters in five species (guinea...
Cited By24
Newest
Published on Sep 1, 2019in Seminars in Cell & Developmental Biology5.46
Wenting Guo5
Estimated H-index: 5
(Katholieke Universiteit Leuven),
Katarina Stoklund Dittlau (Katholieke Universiteit Leuven), Ludo Van Den Bosch43
Estimated H-index: 43
(Katholieke Universiteit Leuven)
Abstract Because of the extremely polarized morphology, the proper functioning of neurons largely relies on the efficient cargo transport along the axon. Axonal transport defects have been reported in multiple neurodegenerative diseases as an early pathological feature. The discovery of mutations in human genes involved in the transport machinery provide a direct causative relationship between axonal transport defects and neurodegeneration. Here, we summarize the current genetic findings related...
Published on Jul 1, 2019in NeuroImage5.81
Shai Berman2
Estimated H-index: 2
(HUJI: Hebrew University of Jerusalem),
S. Filo (HUJI: Hebrew University of Jerusalem), Aviv Mezer15
Estimated H-index: 15
(HUJI: Hebrew University of Jerusalem)
Abstract Conduction of action potentials along myelinated axons is affected by their structural features, such as the axonal g-ratio, the ratio between the inner and outer diameters of the myelin sheath surrounding the axon. The effect of g-ratio variance on conduction properties has been quantitatively evaluated using single-axon models. It has recently become possible to estimate a g-ratio weighted measurement in vivo using quantitative MRI. Nevertheless, it is still unclear whether the varian...
Published on Mar 1, 2019in Journal of Research on Adolescence2.07
Anne-Lise Goddings9
Estimated H-index: 9
(UCL: University College London),
Anne Lise Goddings (UCL: University College London)+ 2 AuthorsBarbara R. Braams12
Estimated H-index: 12
(Harvard University)
Over the past two decades, there has been a tremendous increase in our understanding of structural and functional brain development in adolescence. However, understanding the role of puberty in this process has received much less attention. This review examines this relationship by summarizing recent research studies where the role of puberty was investigated in relation to brain structure, connectivity, and task-related functional magnetic resonance imaging (fMRI). The studies together suggest ...
Published on Jan 24, 2019in International Journal of Impotence Research1.25
Gwang-Won Kim7
Estimated H-index: 7
(Chonnam National University),
Yun-Hyeon Kim11
Estimated H-index: 11
(Chonnam National University)
+ 1 AuthorsGwang-Woo Jeong11
Estimated H-index: 11
(Chonnam National University)
Cross-sex hormones in female-to-male (FtM) transsexuals play a crucial role in brain plasticity. Morphological study associated with white matter (WM) volume in postoperative FtM transsexuals receiving cross-sex hormones has not been published yet. This study was performed to discriminate the regional WM volume differences between postoperative FtM transsexuals and female controls using voxel-based morphometry (VBM) and further to assess the correlations between regional volume variations and cr...
Published on Dec 11, 2018in bioRxiv
Tong Wang8
Estimated H-index: 8
(UQ: University of Queensland),
Wei Li (UQ: University of Queensland)+ 8 AuthorsVictor Anggono18
Estimated H-index: 18
(UQ: University of Queensland)
Most mammalian neurons have a narrow axon, which constrains the passage of large cargoes such as autophagosome as they can be larger than the axon diameter. Variations in tension must therefore occur radially to facilitate changes in axonal diameter and ensure efficient axoplasmic trafficking. Here, we reveal that the transit of diverse large membrane-bound cargoes causes an acute, albeit transient, radial expansion of the axonal diameter, which is immediately restored by constricting forces. We...
Published on Feb 1, 2018in Experimental Neurology4.56
Jean-Pierre Dollé1
Estimated H-index: 1
(UPenn: University of Pennsylvania),
Andrew Jaye1
Estimated H-index: 1
(UPenn: University of Pennsylvania)
+ 3 AuthorsDouglas H. Smith72
Estimated H-index: 72
(UPenn: University of Pennsylvania)
Abstract Since traumatic axonal injury (TAI) is implicated as a prominent pathology of concussion, we examined potential sex differences in axon structure and responses to TAI. Rat and human neurons were used to develop micropatterned axon tracts in vitro that were genetically either male or female. Ultrastructural analysis revealed for the first time that female axons were consistently smaller with fewer microtubules than male axons. Computational modeling of TAI showed that these structural di...
Published on Nov 14, 2017in Frontiers in Human Neuroscience2.87
Maiko Abel Schneider3
Estimated H-index: 3
(UFRGS: Universidade Federal do Rio Grande do Sul),
Poli Mara Spritzer29
Estimated H-index: 29
(UFRGS: Universidade Federal do Rio Grande do Sul)
+ 9 AuthorsMauricio Anés7
Estimated H-index: 7
Introduction: Gender dysphoria (GD) (DMS-5) is a condition marked by increasing psychological suffering that accompanies the incongruence between one's experienced or expressed gender and one's assigned gender. Manifestation of GD can be seen early on during childhood and adolescence. During this period, the development of undesirable sexual characteristics marks an acute suffering of being opposite to the sex of birth. Pubertal suppression with gonadotropin releasing hormone analogs (GnRHa) has...
Published on Aug 1, 2017in NeuroImage5.81
Jennifer S. W. Campbell13
Estimated H-index: 13
(École Polytechnique de Montréal),
Ilana R. Leppert11
Estimated H-index: 11
(Montreal Neurological Institute and Hospital)
+ 5 AuthorsNikola Stikov13
Estimated H-index: 13
(École Polytechnique de Montréal)
Abstract The fiber g-ratio is the ratio of the inner to the outer diameter of the myelin sheath of a myelinated axon. It has a limited dynamic range in healthy white matter, as it is optimized for speed of signal conduction, cellular energetics, and spatial constraints. In vivo imaging of the g-ratio in health and disease would greatly increase our knowledge of the nervous system and our ability to diagnose, monitor, and treat disease. MRI based g-ratio imaging was first conceived in 2011, and e...
Published on Jun 1, 2017in NeuroImage5.81
Shai Berman2
Estimated H-index: 2
(HUJI: Hebrew University of Jerusalem),
Kathryn L. West6
Estimated H-index: 6
(Vandy: Vanderbilt University)
+ 2 AuthorsAviv Mezer15
Estimated H-index: 15
(HUJI: Hebrew University of Jerusalem)
Abstract Recent years have seen a growing interest in relating MRI measurements to the structural-biophysical properties of white matter fibers. The fiber g-ratio, defined as the ratio between the inner and outer radii of the axon myelin sheath, is an important structural property of white matter, affecting signal conduction. Recently proposed modeling methods that use a combination of quantitative-MRI signals, enable a measurement of the fiber g-ratio in vivo. Here we use an MRI-based g-ratio e...
View next paperIn vivo histology of the myelin g-ratio with magnetic resonance imaging