Rolls, Asya
<p>Mar 07, 2018 03:54 PM</p>
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see her Sept 29 2017 lecture... my notes. Technion asst prof. and HHMI intl scholar.</p>
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Dr. Rolls is an HHMI-Wellcome Trust International Scholar and Assistant Professor at Technion, Israel Institute of Technology.</p>
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Abstract: Thoughts and emotions, can impact physiology. This connection is evident by the emergence of disease following stress, or recovery in response to placebo treatment. Nevertheless, this fundamental aspect of physiology remains largely unexplored. We have recently shown that activity of the brain’s reward system, which is active during positive emotional states and positive expectations, boosts anti-bacterial immunity. In this talk, I will discuss how brain activity can regulate anti-tumor immunity and the potential implications to cancer therapy. Given the crucial role of the reward system in emotional processes, our findings offer a new mechanistic insight to the association between the patient’s psychological state and cancer progression.
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ROLLS, Asya, Immunity and the Brain, Technion, Sept 29, 2017
she is from Russia originally. now in Israel.
Brain and immune system...
my seatmate is Brad Zuchero
postponing sickness eg until April 16th after tax time...
how do placebos work?
(Rolls his her husbands last name)
she shows machine to pull out diseases from patients.
in London in 18th century...
this was first placebo trial.
<b>in 1801 by John Haygarth</b>...
the wonderful and powerful influence of the passions of the mind on physiology...
a quote from Haygarth...
conditioning learning a la Pavlov...
eg give saccharine andthen immunosuppresive drug
expectation is important...
fMRI.... reward system is activated during placebo.
she cites Einstein
"everything should be made as simple as possible, not simpler.
her work is done in mice....
<b>what does activation of the reward system do to the immune system</b>...
DREADDs...
we use AAV and thereby manipulate VTA DA neurons
one group of mice gets DREADD and other not
in cre-dep mice.inject with CNO and can
activate the reward system in mice
prove it by place conditioning (sides of cage)
population of monocytes.
VTA activation...
incubate monocytes with E Coli...
yes...<b> just by activating the monocytes they were more potent in killing bacteria...</b>
<b>stronger phagocytosis in VTA activated monocytes</b>.
but why?
what are natural rewards... feeding and mating...
and both expose you to infection...
do reward system activ in mouse then in 24 hours expose to E coli
and then wait 30 days...
get stronger inflammation in VTA activ mice.
immune system can also affect cancer...
<b>immune system plays central role in fighting cancer</b>...
her Expt:
activ
inject mice with tumor in controls and in mice that got CNO injection
to manip reward system.
but how does this work (obvious decr in size of tumors in VTA activ mice)
<b>
we focus on sympath NS.
</b>
it innervates all immune organs.
and is affected by reward system.
is SNS = sympath NS involved?
we killed sympathetic system with 6 OH DA ablation...
we looked at blood, spleen, marrow and at tumor...
and also at corticosterone and noradren levels.
we found reduced noradren. in bone marrow.
but not in the tumor...
how is marrow relevant?
MDSC myeloid ... stem cells.
they inhibit the anti-tumor immune response with T cells and NK cells
they do have beta receptors... ADRB2
from tumor we extracted the MDSCs and combine with tumor...
yes... sufficient to mediate these effect (but prob many mechs)
what changed in MDSCs?
perhaps an effect on TNF... tumor necrosis factor.
next we incubate MDSC with beta agonist.
yes... there is less TNF alpha in presence of beta agonist.
yes... with VTA inhibition then get bigger tumors.
VTA system can affect the antitumor response.
now on to HIV
strudies CCR5 levels inmice after mating?
CCR5 levels on CD4 T cells incr in the blood of males follwoing mating...
but then Tamara put in females that were not receptive...
no effect if females are not receptive.
but NO foreplay in these species if not receptive.
the presence of the female elevated CCR5 even when
female and male were separate... just be mating foreplay.
then we activ with DREADD and also got elev CCR5.
so what is the mechanism?
is it via opioids?
so, we how does activ of reward system boost antibact immunity, etc.
but the immune system also talks back to the brain...
work of Ben Korin...
which immune cells in the brain?...
we use antibodies coupled to fluorophores...
but now we also couple to metal ions...
we use SPADE and... to determine which populations
of immune cells are in the brain...
but were they in the brain or in the blood.
yes... <b>most of immune cells are actually in the brain </b>and not just
leaking in thru blood contam of the sample.
activ of reward system affects the immune system...
but why connected?
what can brain offer to the immune system...
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the brain can PREDICT</b>!!! (unlike the actual immune system which is simply reactive)
and brain has other info...
eg where the predators....
<b>and social environment is crucial</b>...
if lots of social interactions then need anti viral against infections
shows caduceus... integrated medicine.
but if isolated then perhaps woulds are mos timportant.
synchronization eg with SLEEP/ daylight... circadian rhythms...
shows a statue with the arms lifting the head off......
huge group...
Q from Brad Zuchero... can you do better than the placebo?
she is thinking about biofeedback and TMS
broad funding from HHMI, Wellcome, European Res Council, etc.
Q/comment ... parasymp can also have big effect
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