Vermont Genetics Network Annual Retreat August 7 2013 Mark D Spritzer Department of Biology Middlebury College Hormones Adult neurogenesis Spatial cognition Social interactions Adult ID: 182540
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Effects of testosterone and social interactions on adult neurogenesis in male rats. Vermont Genetics Network Annual Retreat, August 7 2013Mark D. SpritzerDepartment of Biology, Middlebury CollegeSlide2
Hormones
Adult neurogenesis
Spatial cognition
Social interactionsSlide3
Adult Neurogenesis
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.
Aimone
et al. 2006Slide4
Hippocampus
The rat hippocampus
Dentate
Gyrus
CA1
CA3
CA2
Granule
cell layer
HilusSlide5
GCL
hilus
Cell proliferation
Cell survival
hilus
gcl
100
m
10
m
hilus
gclSlide6
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).Slide7
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).Slide8
Testosterone and hippocampal neurogenesisTestosterone has no effect on cell proliferation (Spritzer & Galea 2007; Carrier & Kabbaj 2012; 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?Slide9
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 Slide10
High dose of testosterone increased neurogenesisSlide11
Sex and hippocampal neurogenesisAggressive 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?Slide12
MethodsSlide13
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
Slide14
Sexual interactions had no effect on neurogenesisSlide15
Testosterone increases only on first day of sexual interactions.Slide16
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.Slide17
Thank You!Middlebury students: Kelsey Calhoun, Shannon Engelman, Zach Schneider-Lynch, Ethan Roy, Leanne ShulmanCollaborators: Liisa Galea, Jennifer BarkerFunding
:
Middlebury College, Department of Biology, Sigma Xi, Vermont Genetics NetworkSlide18
Effects similar in dorsal and ventral hippocampus
Dorsal GCL
Ventral GCLSlide19
Male sexual behavior cycles!