title: Axon diameter and axonal transport: In vivo and in vitro effects of androgens.
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.
authors.affiliation: Rotman Research Institute, University of Toronto, 3560 Bathurst Street, Toronto, Ontario M6A 2E1, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Pesaresi
authors.affiliation: Rotman Research Institute, University of Toronto, 3560 Bathurst Street, Toronto, Ontario M6A 2E1, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Soon-Shiong
authors.affiliation: Rotman Research Institute, University of Toronto, 3560 Bathurst Street, Toronto, Ontario M6A 2E1, Canada.
authors.forename: L
authors.initials: L
authors.lastname: French
authors.affiliation: Program in Neuroscience and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: D R
authors.initials: DR
authors.lastname: Kaplan
authors.affiliation: Program in Neuroscience and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: F D
authors.initials: FD
authors.lastname: Miller
authors.affiliation: Rotman Research Institute, University of Toronto, 3560 Bathurst Street, Toronto, Ontario M6A 2E1, Canada. Electronic address: tpaus@research.baycrest.org.
authors.forename: T
authors.initials: T
authors.lastname: Paus
mesh_terms: D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D001370:Axonal Transport / Q000187:drug effects* / Q000502:physiology*; D001369:Axons / Q000187:drug effects* / Q000648:ultrastructure*; D003337:Corpus Callosum / Q000187:drug effects / Q000648:ultrastructure; D004305:Dose-Response Relationship, Drug; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D009277:Nandrolone / Q000031:analogs & derivatives / Q000494:pharmacology; D009919:Orchiectomy; D010052:Ovariectomy; D061251:Primary Cell Culture; D051381:Rats; D017208:Rats, Wistar; D012727:Sex Characteristics; D013739:Testosterone / Q000494:pharmacology; D066127:White Matter / Q000033:anatomy & histology / Q000187:drug effects
chemical_list: D000728:Androgens; D013739:Testosterone; D009277:Nandrolone; C100075:mibolerone
keywords: Axon; Axon transport; Myelin; Testosterone; White matter