r.i.p. steve jobs

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R.I.P. Steve Jobs

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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 - PowerPoint PPT Presentation

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Page 1: R.I.P. Steve Jobs

R.I.P. Steve Jobs

Page 2: R.I.P. Steve Jobs

Hao LiOct.7th 2011

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Social Defeat ParadigmSocial Defeat Paradigm

Long–Evans rats

(325–350 g)

Sprague–Dawley

rats(250–275 g)

V.S.

Social Defeat Paradigm

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Social Defeat ParadigmSocial Defeat Paradigm5 min fighting or until the

submissionSeparated with wire mesh cage

for 15 min4 consecutive encounters15 min between each encounters

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

AnhedoniaForced swim test---- Behavioral

DespairContextual fear test----MemorySocial approach and avoidance

test

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Sucrose preference testSucrose preference test2 bottles water for 5 days

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

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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

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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

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Histone ModificationHistone ModificationHistone acetylation makes RNA

polymerase and transcription factors easier to access the promoter region.

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Histone ModificationHistone ModificationHistone H3Histone H4

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Histone ModificationHistone Modification• H3 Acetylation

Electroconvulsive Seizures

• H4 Acetylation

Upregulation of BDNF Transcription

Downregulation of c-fos Transcription

(Tsankova 2004)

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Behavioral TestsBehavioral Tests

Sucrose Preference Test: Both defeated and control rats

similarly preferred increasing sucrose concentrations over water.

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Behavioral TestsBehavioral Tests

Forced Swim Test:

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Behavioral TestsBehavioral Tests

Social approach and avoidance test

Section 1 Section 2

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Behavioral TestsBehavioral Tests

Section 3

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Behavioral TestsBehavioral Tests

Contextual fear test:

4 weeks 6 weeks

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Sucrose preference testForced swim testContextual fear testSocial approach and avoidance test

Depressive-like Behaviors

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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

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Histone ModificationHistone Modification

hippocampus

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No changes in H4 acetylation and H3 acetylation in the amygdala or dorsal prefrontal cortex

----Highly heterogeneous region----Lack of antibody specificity

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Histone ModificationHistone ModificationTwo potential pathways in histone

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

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

changes Former study

showed both of them

blocked the acetylation

Different changes to different stressors

(Chandramohan Y 2007)

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Thanks…