Poster Presentation The International Congress of Neuroendocrinology 2014

Adolescent testosterone and postnatal Hippocampal Neurogenesis in male rats (#190)

Katie M Allen 1 2 3 , Tertia D Purves-Tyson 2 3 4 , Danny Boerrigter 2 3 , Cyndi Shannon Weickert 1 2 3
  1. Department of Psychiatry, UNSW, Sydney, NSW, Australia
  2. Neuroscience Research Australia, Randwick, NSW, Australia
  3. Schizophrenia Research Institute, Sydney, NSW, Australia
  4. Department of Medical Sciences, University of New South Wales, Sydney, NSW, Australia

Background: Schizophrenia has its peak diagnosis in young adult males, suggesting that changes in testosterone may trigger neurobiological changes associated with schizophrenia, such as decreased neurogenesis. The influence of sex steroids on post-natal neurogenesis depends on the timing and duration of hormone exposure. We have previously shown in monkeys that adolescent testosterone decreases hippocampal cell survival and markers of immature neurons, without influencing proliferation. In this study, we sought to determine the effect of adolescent gonadectomy and sex steroid replacement on postnatal cell proliferation, survival and differentiation in male rats.  

Methods: Male Sprague Dawley rats (45 days old, n~15/group) were gonadectomised (Gdx), sham operated (Intact), gonadectomised and given testosterone implant (Gdx + T), dihydrotestosterone implant (Gdx + DHT), or estradiol implant (Gdx + E) and sacrificed at 60 days old. The hippocampus was removed, total RNA isolated and cDNA synthesised. The mRNA expression of proliferative (Ki67) and neuronal markers [Tuc4 and Doublecortin (Dcx)] was quantified by RT-PCR (qPCR).

Results: Two weeks of gonadectomy did not alter Ki67, Dcx or Tuc4 mRNA expression in comparison to intact rats. However there was a strong trend for testosterone replacement to decrease Ki67 expression compared to non-replaced gdx rats (t(25)=2.01, p=0.055). DHT or estradiol did not alter expression of any marker compared to intact rats.

Conclusions: We suggest that short-term testosterone replacement downregulates cell proliferation (Ki67 mRNA expression) in adolescent male rats. In contrast to monkeys, we did not detect a change in markers of immature neurons, which may be due to differences in the timing or neurogenesis across species. Future studies will investigate if longer-term gonadectomy (six weeks) and testosterone replacement impacts cell proliferation (Ki67), cell survival [Bromodeoxyuridine(BrdU)] and/or markers of immature neurons (Dcx and BrdU/Prox1) in young adult male rats.