title: The effect of adolescent testosterone on hippocampal BDNF and TrkB mRNA expression: relationship with cell proliferation.
abstract: BACKGROUND
  Testosterone attenuates postnatal hippocampal neurogenesis in adolescent male rhesus macaques through altering neuronal survival. While brain-derived neurotropic factor (BDNF)/ tyrosine kinase receptor B (TrkB) are critical in regulating neuronal survival, it is not known if the molecular mechanism underlying testosterone's action on postnatal neurogenesis involves changes in BDNF/TrkB levels. First, (1) we sought to localize the site of synthesis of the full length and truncated TrkB receptor in the neurogenic regions of the adolescent rhesus macaque hippocampus. Next, (2) we asked if gonadectomy or sex hormone replacement altered hippocampal BDNF and TrkB expression level in mammalian hippocampus (rhesus macaque and Sprague Dawley rat), and (3) if the relationship between BDNF/TrkB expression was altered depending on the sex steroid environment.
  
  
  RESULTS
  We find that truncated TrkB mRNA+ cells are highly abundant in the proliferative subgranular zone (SGZ) of the primate hippocampus; in addition, there are scant and scattered full length TrkB mRNA+ cells in this region. Gonadectomy or sex steroid replacement did not alter BDNF or TrkB mRNA levels in young adult male rat or rhesus macaque hippocampus. In the monkey and rat, we find a positive correlation with cell proliferation and TrkB-TK+ mRNA expression, and this positive relationship was found only when sex steroids were present.
  
  
  CONCLUSIONS
  We suggest that testosterone does not down-regulate neurogenesis at adolescence via overall changes in BDNF or TrkB expression. However, BDNF/TrkB mRNA appears to have a greater link to cell proliferation in the presence of circulating testosterone.
authors.affiliation: Schizophrenia Research Institute, Sydney, Australia. k.allen@neura.edu.au.|Schizophrenia Research Laboratory, Neuroscience Research Australia, Barker Street, Randwick, NSW, 2031, Australia. k.allen@neura.edu.au.|School of Psychiatry, University of New South Wales, Sydney, Australia. k.allen@neura.edu.au.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Allen
authors.affiliation: Schizophrenia Research Institute, Sydney, Australia. t.purves-tyson@neura.edu.au.|Schizophrenia Research Laboratory, Neuroscience Research Australia, Barker Street, Randwick, NSW, 2031, Australia. t.purves-tyson@neura.edu.au.|School of Medical Sciences, University of New South Wales, Sydney, Australia. t.purves-tyson@neura.edu.au.
authors.forename: Tertia D
authors.initials: TD
authors.lastname: Purves-Tyson
authors.affiliation: Schizophrenia Research Institute, Sydney, Australia. s.fung@neura.edu.au.|Schizophrenia Research Laboratory, Neuroscience Research Australia, Barker Street, Randwick, NSW, 2031, Australia. s.fung@neura.edu.au.|School of Psychiatry, University of New South Wales, Sydney, Australia. s.fung@neura.edu.au.
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Fung
authors.affiliation: Schizophrenia Research Institute, Sydney, Australia. cyndi@neura.edu.au.|Schizophrenia Research Laboratory, Neuroscience Research Australia, Barker Street, Randwick, NSW, 2031, Australia. cyndi@neura.edu.au.|School of Psychiatry, University of New South Wales, Sydney, Australia. cyndi@neura.edu.au.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Shannon Weickert
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D001973:Bromodeoxyuridine; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism*; D020249:Hormone Replacement Therapy; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D019394:Ki-67 Antigen / Q000378:metabolism; D008253:Macaca mulatta; D008297:Male; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology; D009919:Orchiectomy; D012333:RNA, Messenger / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020813:Receptor, trkB / Q000378:metabolism*; D013045:Species Specificity; D055153:Stem Cell Niche / Q000187:drug effects / Q000502:physiology; D013739:Testosterone / Q000008:administration & dosage / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D019394:Ki-67 Antigen; D012333:RNA, Messenger; D013739:Testosterone; D020813:Receptor, trkB; D001973:Bromodeoxyuridine