title: Adolescent testosterone influences BDNF and TrkB mRNA and neurotrophin-interneuron marker relationships in mammalian frontal cortex.
abstract: Late adolescence in males is a period of increased susceptibility for the onset of schizophrenia, coinciding with increased circulating testosterone. The cognitive deficits prevalent in schizophrenia may be related to unhealthy cortical interneurons, which are trophically dependent on brain derived neurotrophic factor. We investigated, under conditions of depleted (monkey and rat) and replaced (rat) testosterone over adolescence, changes in gene expression of cortical BDNF and TrkB transcripts and interneuron markers and the relationships between these mRNAs and circulating testosterone. Testosterone removal by gonadectomy reduced gene expression of some BDNF transcripts in monkey and rat frontal cortices and the BDNF mRNA reduction was prevented by testosterone replacement. In rat, testosterone replacement increased the potential for classical TrkB signalling by increasing the full length to truncated TrkB mRNA ratio, whereas in the monkey cortex, circulating testosterone was negatively correlated with the TrkB full length/truncated mRNA ratio. We did not identify changes in interneuron gene expression in monkey frontal cortex in response to gonadectomy, and in rat, we showed that only somatostatin mRNA was decreased by gonadectomy but not restored by testosterone replacement. We identified complex and possibly species-specific, relationships between BDNF/TrkB gene expression and interneuron marker gene expression that appear to be dependent on the presence of testosterone at adolescence in rat and monkey frontal cortices. Taken together, our findings suggest there are dynamic relationships between BDNF/TrkB and interneuron markers that are dependent on the presence of testosterone but that this may not be a straightforward increase in testosterone leading to changes in BDNF/TrkB that contributes to interneuron health.
authors.affiliation: Schizophrenia Research Institute, Sydney 2021, Australia; Neuroscience Research Australia, Sydney 2031, Australia; School of Medical Sciences, University of New South Wales, Sydney 2031, Australia.
authors.forename: Tertia D
authors.initials: TD
authors.lastname: Purves-Tyson
authors.affiliation: Schizophrenia Research Institute, Sydney 2021, Australia; Neuroscience Research Australia, Sydney 2031, Australia; School of Psychiatry, University of New South Wales, Sydney 2031, Australia.
authors.forename: Katherine
authors.initials: K
authors.lastname: Allen
authors.affiliation: Schizophrenia Research Institute, Sydney 2021, Australia; Neuroscience Research Australia, Sydney 2031, Australia; School of Psychiatry, University of New South Wales, Sydney 2031, Australia.
authors.forename: Samantha
authors.initials: S
authors.lastname: Fung
authors.affiliation: Schizophrenia Research Institute, Sydney 2021, Australia; Neuroscience Research Australia, Sydney 2031, Australia.
authors.forename: Debora
authors.initials: D
authors.lastname: Rothmond
authors.affiliation: NIMH IRP Non-Human Primate Core, MD, USA.
authors.forename: Pam L
authors.initials: PL
authors.lastname: Noble
authors.affiliation: ANZAC Research Institute, Concord 2139, Australia.
authors.forename: David J
authors.initials: DJ
authors.lastname: Handelsman
authors.affiliation: Schizophrenia Research Institute, Sydney 2021, Australia; Neuroscience Research Australia, Sydney 2031, Australia; School of Psychiatry, University of New South Wales, Sydney 2031, Australia.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Shannon Weickert
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D005625:Frontal Lobe / Q000254:growth & development* / Q000378:metabolism*; D006728:Hormones / Q000008:administration & dosage; D007395:Interneurons / Q000378:metabolism*; D008253:Macaca mulatta; D008297:Male; D009414:Nerve Growth Factors / Q000378:metabolism; D009919:Orchiectomy; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020813:Receptor, trkB / Q000378:metabolism*; D013004:Somatostatin / Q000378:metabolism; D013045:Species Specificity; D013739:Testosterone / Q000008:administration & dosage / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D006728:Hormones; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D013739:Testosterone; D013004:Somatostatin; D020813:Receptor, trkB
keywords: Adolescence; Brain derived neurotrophic factor; Cortical interneurons; Rat; Rhesus macaque; Testosterone