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

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 H3 Acetylation Electroconvulsive Seizures H4 Acetylation Upregulation of BDNF Transcription Downregulation of c-fos Transcription (Tsankova 2004)

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 1 Section 2

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 the ratio of histone H3 acetylation (H3hyp) to total histone H3 (TH3) amygdala dorsal prefrontal cortex

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 increasing acetylation Mifepristone----no significant changes Former study showed both of them blocked the acetylation Different changes to different stressors (Chandramohan Y 2007)

Thanks…