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Effects of testosterone and social interactions on adult neurogenesis in male rats .

Effects of testosterone and social interactions on adult neurogenesis in male rats . Vermont Genetics Network Annual Retreat, August 7 2013 Mark D. Spritzer Department of Biology, Middlebury College. Hormones. Social interactions. Spatial cognition. Adult neurogenesis.

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Effects of testosterone and social interactions on adult neurogenesis in male rats .

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  1. Effects of testosterone and social interactions on adult neurogenesis in male rats. Vermont Genetics Network Annual Retreat, August 7 2013 Mark D. Spritzer Department of Biology, Middlebury College

  2. Hormones Social interactions Spatial cognition Adult neurogenesis

  3. Adult Neurogenesis Aimone et al. 2006 • Proliferation, survival, and differentiation of new neurons from stem cells in adult brain. • Occurs mainly in dentate gyrus and sub-ventricular zone. • Measured using thymidine analogs (BrdU) or endogenous markers.

  4. Hippocampus CA1 Dentate Gyrus CA2 CA3 Granule cell layer Hilus The rat hippocampus

  5. Cell proliferation gcl hilus 10 m hilus GCL hilus gcl 100 m Cell survival

  6. Neurogenesis is necessary for forming spatial memories • Environmental enrichment improves spatial learning and memory and increases neuron survival (Kempermann et al. 1997; van Praag et al. 1999). • Chronic stress impairs adult neurogenesis and spatial learning and memory (Mirescu & Gould 2006; Stranahan et al. 2006). • Rats given spatial learning task have increased neuron survival (Epp et al. 2008; Gould et al. 1999). • Blocking neurogenesis impairs spatial memory • Irradiation of hippocampus(Raber et al. 2004; Snyder et al. 2005). • Transgenic mice(Dupret et al. 2008; Jessberger et al. 2009).

  7. Reduced neurogenesis is symptomatic of disease • Age-related dementia • Aging impairs spatial memory and reduces neurogenesis (Drapeau et al. 2003). • Hippocampus is key site of neurodegeneration in Alzheimer’s disease (Steiner et al. 2006). • Neurogenesis dysregulated in AD patients (Arendt 2000; Li et al. 2007). • Chronic depression • Chronic stress reduces neurogenesis and is correlated with increase risk of depression (Diamond et al. 1996; Pham et al. 2003 ). • Antidepressants enhance neurogenesis (Duman & Monteggia 2006).

  8. Testosterone and hippocampal neurogenesis • Testosterone has no effect on cell proliferation (Spritzer & Galea 2007; Carrier & Kabbaj2012; Ho et al. 2012). • Castration reduces adult neurogenesis in male rats via decreased cell survival (Spritzer & Galea 2007; Wainwright et al. 2011). • 30 days of testosterone injections enhanced neurogenesis in castrated male rats via an androgen- dependent pathway (Spritzer & Galea 2007). • Effects of castration only observed in socially isolated rats (Spritzer et al. 2011). • Rats lacking androgen receptors show no change in neurogenesis in response to testosterone implants (Hamson et al. 2013). How does testosterone influence different stages of neural development?

  9. Methods • 9 groups of adult male rats(N = 8/group) • 3 injection doses: Oil, 0.250 mg, 0.500 mg • 3 time periods: cell proliferation • axon extension • neuron maturation • All groups injected with 200 mg/kg BrdU on Day 0 • All groups perfused 16 days after BrdU injection

  10. High dose of testosterone increased neurogenesis

  11. Sex andhippocampal neurogenesis • Aggressive interactions cause a decrease in neurogenesis among subordinates (Kozorovitskiy & Gould 2004; Thomas et al. 2007). • Sexual interactions enhance neurogenesis in female mice (Shingo et al. 2003). • Single sexual interaction enhanced cell proliferation and 14 days of sex prior to BrdU injections enhanced neurogenesis in male rats (Leuner et al. 2010; Glasper & Gould 2013). How does sex influence different stages of neural development?

  12. Methods

  13. Methods • 4 groups of adult male rats(N = 10-12/group) • - Control: no sexual interactions • - Experimental: 5 days of 30 min sexual interactions with estrus female on specified days. • All groups injected with 200 mg/kg BrdU on Day 0 • All groups perfused 16 days after BrdU injection

  14. Sexual interactions had no effect on neurogenesis

  15. Testosterone increases only on first day of sexual interactions.

  16. Conclusions • High dose (0.500 mg T) of short duration (5 days) increased adult neurogenesis. • Later stages of neural development may be more strongly impacted by testosterone? • Acute bouts of sexual interactions have no effect on adult neurogenesis. • Testosterone is increased only on first day of a series of sexual interactions.

  17. Thank You! • Middlebury students:Kelsey Calhoun, Shannon Engelman, Zach Schneider-Lynch, Ethan Roy, Leanne Shulman • Collaborators: Liisa Galea, Jennifer Barker • Funding: Middlebury College, Department of Biology, Sigma Xi, Vermont Genetics Network

  18. Effects similar in dorsal and ventral hippocampus Dorsal GCL Ventral GCL

  19. Male sexual behavior cycles!

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