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R.I.P. Steve Jobs. Hao Li Oct.7 th 2011. Social Defeat Paradigm. Long–Evans rats (325–350 g). Sprague–Dawley rats(250–275 g). V.S. Social Defeat Paradigm. Social Defeat Paradigm. 5 min fighting or until the submission Separated with wire mesh cage for 15 min 4 consecutive encounters
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Hao Li Oct.7th 2011
Social Defeat Paradigm Long–Evans rats (325–350 g) Sprague–Dawley rats(250–275 g) V.S. Social Defeat Paradigm
Social Defeat Paradigm • 5 min fighting or until the submission • Separated with wire mesh cage for 15 min • 4 consecutive encounters • 15 min between each encounters
Depressive-like Behaviors • Sucrose preference test----Anhedonia • Forced swim test----Behavioral Despair • Contextual fear test----Memory • Social approach and avoidance test
Sucrose preference test 2 bottles water for 5 days Increasing concentrations of sucrose (0.25–1%) for 2 days per concentration
Contextual fear test • For the memory of traumatic event • Putting the rats and an aggressor in the same cage for 5 min • Measuring the freezing time
Social approach and avoidance • 3 sections each for 5 min • Section 1- free walks in the open field • Section 2- “no target” • Section 3- “target” • Measuring the locomotion and investigating time
Histone Modification • Histone acetylation makes RNA polymerase and transcription factors easier to access the promoter region.
Histone Modification • Histone H3 • Histone H4
Histone Modification Upregulation of BDNF Transcription Downregulation of c-fos Transcription (Tsankova 2004) • H3 Acetylation Electroconvulsive Seizures • H4 Acetylation
Behavioral Tests Sucrose Preference Test: Both defeated and control rats similarly preferred increasing sucrose concentrations over water.
Behavioral Tests Forced Swim Test:
Behavioral Tests Social approach and avoidance test Section 2 Section 1
Behavioral Tests Section 3
Behavioral Tests Contextual fear test: 4 weeks 6 weeks
Sucrose preference test Forced swim test Contextual fear test Social approach and avoidance test Depressive-like Behaviors
Histone Modification • No significant changes in H3 acetylation in amygdala and dorsal profrontal cortex amygdala dorsal prefrontal cortex the ratio of histone H3 acetylation (H3hyp) to total histone H3 (TH3)
Histone Modification hippocampus
No changes in H4 acetylation and H3 acetylation in the amygdala or dorsal prefrontal cortex ----Highly heterogeneous region ----Lack of antibody specificity
Histone Modification • Two potential pathways in histone acetylation: N-methyl-D-aspartic acid receptor (NMDA-R) glucocorticoid receptor (GR)
MK-801----increasing acetylation • Mifepristone----no significant changes Former study showed both of them blocked the acetylation (Chandramohan Y 2007) Different changes to different stressors