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Printable Handouts
Navigable Slide Index
- Introduction
- Acknowledgements
- Disclosures
- Depression is a major public health problem
- Where is the light?
- Current problems and solutions
- Remission is harder to achieve with each treatment failure
- Antidepressant drugs?
- Possible sites of antidepressant action
- Long-term increase in cAMP and P-CREB accompany antidepressant treatment (1)
- Long-term increase in cAMP and P-CREB accompany antidepressant treatment (2)
- G proteins
- G protein signaling
- GPCR schema
- Serotonin receptor GPCR signaling
- Olanzapine, a “5HT2A antagonist” and psychedelic
- Serotonin receptor GPCR signaling
- Lipid rafts compartmentalize neurotransmitter signaling
- Organization of signaling components into lipid rafts and caveolae
- Long-term increase in cAMP and P-CREB accompany antidepressant treatment (3)
- Hypothesis
- Agents that translocate Gsα from lipid rafts and augment Gs/AC coupling
- GFP-Gsα is plasma membrane-delimited and shows a “patchy” distribution
- Internalized Gsα-GFP colocalizes with the lipid raft marker cholera toxin B
- Gsα modulation of microtubule dynamics
- Gsα-GFP in living PC12 cells
- Overexpression of constitutively activated Gsα
- Translocation of Gsα from lipid rafts
- Fluorescence Recovery After Photobleaching (FRAP)
- The mobility of GFP-Gsα in C6 glioma cells
- GFP-Gsα FRAP results for various psychotropic compounds
- Overall cAMP increases but lipid raft cAMP decreases in response to antidepressant
- Acute ketamine treatment induced changes in Gsα lipid raft localization
- NMDAR independence for ketamine translocation of Gsα/AC activation
- Antidepressant treatment moves Gsα out of rafts/caveolae (1)
- Antidepressants sort, slowly, into lipid rafts
- Antidepressant treatment moves Gsα out of rafts/caveolae (2)
- Acylation status of Gsα affects translocation from lipid rafts
- Sustained antidepressant treatment depalmitoylates Gsα
- Antidepressant treatment moves Gsα out of rafts/caveolae (3)
- Tubastatin-A treatment increases tubulin acetylation
- Lipid-raft α-tubulin is less acetylated in a depressed human brain prefrontal cortex
- Gsα-tubulin interface: A model
- A blood biomarker for depression: Potential Dx properties of Gsα/raft localization
- Conclusions
Topics Covered
- Depression
- Antidepressant drug targets
- G protein signaling
- GPCR
- Gsα lipid raft localization and antidepressant treatment
- Gsα Acylation status and lipid raft localization
- Gsα palmitoylation status and lipid raft localization
- Blood biomarkers for depression
Links
Series:
Categories:
Therapeutic Areas:
Talk Citation
Rasenick, M.M. (2021, November 29). G proteins and the biology of depression and antidepressants [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved November 21, 2024, from https://doi.org/10.69645/CITY8034.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Mark M. Rasenick has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Other Talks in the Series: G Protein-Coupled Receptors (GPCRs) Signaling in Health and Disease
Transcript
Please wait while the transcript is being prepared...
0:00
Hi, I'm Mark Rasenick and welcome to
this installment in the series of talks on
G-proteins, GPCRs and G-proteins signaling.
I'm a professor of physiology, biophysics,
and psychiatry at the University of Illinois College of Medicine,
and also a Research Career Scientist at the Jesse Brown VA Medical Center,
which is adjacent to the University of Illinois campus in Chicago.
Today I'll be talking about G-proteins and the biology of
depression and the biology of antidepressant action.
0:37
The picture you see is my own antidepressant.
I'm out on Lake Michigan on a boat that belongs to someone else,
something I do every Wednesday.
While I'm doing that,
the people on the right have contributed to the data that we're going to discuss today.
The people on the left had been collaborators from
other laboratories that have worked with us to make those data possible.
1:01
These are my disclosures.
The one that's most relevant to what we will be discussing today is PAX Neuroscience,
a startup company that was formed to market the notion of biomarkers for
depression and how they would be used both to help
a diagnosis of depression and to facilitate antidepressant therapy.
1:26
Before we talk about the science,
I want to give an overview as to why we're doing this.
These figures in front of you are figures from the United States.
But basically it doesn't change worldwide.
In the US, we have a constant stream of violence that's always talked about in the news,
and it results in about 13,000 homicides per year;
compare that to the 48,000 suicides we have per year.
In other words, more than three times as many.
One attempt a minute.
As I said, I met a VA Medical Center and 21 veterans per day complete suicide.
Right now, depression is the number one cause of disability in the world.
Depression increases mortality and morbidity from somatic disease.
In other words, if you have heart disease, and you're depressed,
you're more likely to be sicker from or
die from it than you would be if you weren't depressed.
Finally, and most soberingly,
one in six of the people listening to this today either have been,
are, or will be depressed, and that's worldwide.
This is a major public health problem.