r.i.p. steve jobs

R.I.P. Steve Jobs

Hao LiOct.7th 2011

Social Defeat ParadigmSocial Defeat Paradigm

Long–Evans rats

(325–350 g)

Sprague–Dawley

rats(250–275 g)

V.S.

Social Defeat Paradigm

Social Defeat ParadigmSocial Defeat Paradigm5 min fighting or until the

submissionSeparated with wire mesh cage

for 15 min4 consecutive encounters15 min between each encounters

Depressive-like BehaviorsDepressive-like BehaviorsSucrose preference test----

AnhedoniaForced swim test---- Behavioral

DespairContextual fear test----MemorySocial approach and avoidance

test

Sucrose preference testSucrose preference test2 bottles water for 5 days

Increasing concentrations of sucrose (0.25–1%) for 2 days per concentration

Contextual fear testContextual 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 Social approach and avoidanceavoidance3 sections each for 5 minSection 1- free walks in the open

fieldSection 2- “no target” Section 3- “target”

Measuring the locomotion and investigating time

Histone ModificationHistone ModificationHistone acetylation makes RNA

polymerase and transcription factors easier to access the promoter region.

Histone ModificationHistone ModificationHistone H3Histone H4

Histone ModificationHistone Modification• H3 Acetylation

Electroconvulsive Seizures

• H4 Acetylation

Upregulation of BDNF Transcription

Downregulation of c-fos Transcription

(Tsankova 2004)

Behavioral TestsBehavioral Tests

Sucrose Preference Test: Both defeated and control rats

similarly preferred increasing sucrose concentrations over water.

Behavioral TestsBehavioral Tests

Forced Swim Test:

Behavioral TestsBehavioral Tests

Social approach and avoidance test

Section 1 Section 2

Behavioral TestsBehavioral Tests

Section 3

Behavioral TestsBehavioral Tests

Contextual fear test:

4 weeks 6 weeks

Sucrose preference testForced swim testContextual fear testSocial approach and avoidance test

Depressive-like Behaviors

Histone ModificationHistone ModificationNo 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 ModificationHistone 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 ModificationHistone ModificationTwo potential pathways in histone

acetylation: N-methyl-D-aspartic acid receptor (NMDA-R) glucocorticoid receptor (GR)

MK-801----increasing acetylationMifepristone----no significant

changes Former study

showed both of them

blocked the acetylation

Different changes to different stressors

(Chandramohan Y 2007)

Thanks…