Transcript Example: Angiostatin

Psychoneuroimmunology
How our brains and bodies are
linked
Psychoneuroimmunology
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Study of the interaction between psychological
processes and the nervous, immune and
endocrine systems of the body
Incorporates psychology, immunology,
physiology, endocrinology, infectious disease,
rheumatology and molecular biology.
Better name: PENI
(psychoendoneuroimmunology
History
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1975, Dr. Robert Adler demonstrated
through classic conditioning experiments:
Rats were conditioned to associated
saccharin-laced water with the drug
Cytoxan which induces nausea and
suppression of the immune system.
After the conditioning, just feeding the rats
the saccharin water led to death of some
by through a compromised IS.
It’s all a circle
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The immune system can be modulated by
endocrine and neural activity
And it can just as easily influence
endocrine and neural activity
The IS and brain talk to each other
through the hypothalamic-pituitary-adrenal
(HPA) axis, other hormonal pathways and
the sympathetic nervous system (SNS)
In other words:
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We think a thought or experience an
emotion, and our body responds either
with health-enhancing or health-inhibiting
actions
Physical behaviors (i.e. exercise, diet, etc.)
can influence our thoughts and emotions
HPA axis
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Responds to physical, mental and
emotional challenges by controlling
hormonal and neurotransmitters
Many diseases are linked to dis-regulation
of this axis
Review of hormonal terms
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HPA axis
CRH
ACTH
Glucocorticoids
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Corticosterone
Cortisol
Catecholamines
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Epinephrine(adrenaline)
Norepinephrine (noradrenalin)
Review of hormonal terms
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Endorphins and enkephalins
Adrenergic and noradrenergic
Acetylcholine: major neuro-transmitter of
PSN
cholinergic
Review of IS terms
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Immune cells:
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Phagocytes: monocytes, macrophages
Mast cells - trigger inflammatory response
Lymphocytes
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B and T lymphocytes
Interferons - anti-virals
NK cells - anti-viral and cancer cells
Antibodies/immunoglobulins
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Cytokines respond to specific antigens
Interleukins are types of cytokines
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These are not separate
systems!
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Immune cells secrete and have receptors
for hormones, neurotransmitters and
neuropeptides
Neurons have receptors for both
hormones and neurotransmitters
Many hormones behave like
neurotransmitters: they are released from
endocrine and nervous tissue
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Called neuropeptides
Not separate systems, cont’d
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Neuropeptides and classic
neurotransmitters can coexist in the same
neuron
Neuropeptides found in the brain include
hormones previously thought to reside
only in the GI tract, anterior and posterior
pituitary
“The implications of the nervous and endocrine
systems sharing transmitters are enormous and
set the stage for significant interactions with the
immune and stress systems. ..The body houses an
efficient organization not only for the nervous
system to communicate with the hormones of the
endocrine system, or vice versa, but also for the
immune and stress systems to influence and be
influenced by the nervous and endocrine
systems.” Wisneski
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Communication between
brain and immune system
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Epinephrine and Nor-ep generally suppress the
immune system, but enhance it in the CNS,
potentiated by immune cells
Neurons fire more frequently during antibody
response to an immunization, and nor-ep
decreased
IS sends humoral and neural messages to the
brain of intruders, which triggers the HPA axis or
peripheral cytokines
More Brain/IS communication
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Activated immune cells are capable of
permeating the blood brain barrier and
secreting cytokines, which can influence
peripheral neuroendo functions
Communication between
neuroendocrine and IS
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Immune cells respond to signals from the CNS,
thru the HPA axis
Pituitary and adrenal endorphins positively affect
the immune system
Cytokines in the brain influence the HPA axis
Cytokines all cause pituitary-like hormones to be
secreted by Immune cells, modulating pituitary
hormone secretions (some regulate and some
inhibit normal growth and promote tumor growth)
More communication!
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Neuroendo hormones have receptors on and
are produced by immune cells.
CRH encourages leukocytes to secrete ACTH
ACTH decreases antibody production, and
suppresses immune function via glucocorticoid
stimulation (why we get sick when stressed)
T lymphocytes have receptors for enkephalins,
increasing NK cell activity
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Thymus Gland
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Master trainer of immune system: secretes
hormones, is influenced by neurotransmitters,
and regulates immune system
GH, prolactin, ACTH, LH are produced within the
thymus as well as pituitary
These hormones regulate immune action and
influence regulation of the HPA axis
Norepinephrine primary thymus hormone: as we
age, it increases, reducing immune function
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Pineal Gland
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Its sensory receptors are capable of
receiving environmental stimuli and
converting them into action potentials
capable of communicating with the brain.
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Transforms light-dark perception and
transforms it into our circadian rhythm thru
production of melatonin
Melatonin regulates myriad endocrine and
immune functions
Melatonin
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Stimulates immune function and reduces
the deleterious effects of stress
Fits into its own receptor but also into the
benzodiazepine receptors
Immune-boosting effects of melatonin
appear to come from it stimulating Tlymphocyte helper cells that have already
been stimulated by an antigen.
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HPA Axis and Immune System
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IS is a sensory receptor organ that sends
info to CNS through cytokines
Activated CNS structures (hippocampus,
hypothalamus)cause neuroendocrine
immune peripheral effects
Immune system stimulates HPA axis, once
a certain threshold is met (controlling overresponsiveness)
HPA Axis and Immune
System, cont’d
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Activation of the stress response during
injury and illness causes immune
suppression , controlling over-expression
If immune mediators were not checked,
glucocorticoid secretions would shut down
immune system
Crucial to body’s self-regulation
Intercellular communication
in the Anterior Pituitary
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Novel pituitary-like hormones subtly adjust
classic pituitary hormones, thus affecting
function and cell growth.
Overall influence is significant to an
integrated hormonal response
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Galanin influences pituitary secretions, which
affect sexual and growth functions, and
modulate stress and immune response
Summary
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Nervous and endocrine systems share
neurotransmitters
Brain receives and responds to chemical
and electrical info from IS
IS is a sensory organ because it can
obtain, process and send info to CNS
Cytokines are principal mediators of
communication between neuroendocrine
and IS
Summary, cont’d
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Lymphocytes have receptors for hormones
Thymic hormones influence reg of HPA
axis
Bi-directional, afferent-efferent pathway
between the IS and neuroendocrine
systems
Examples of Integration: New
Research
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Neglect stunts brain development, reducing
myelin in pre-frontal cortex (Sept. 14 Science)neurobiological cause of behavioral changes
Signs of depression can be turned on and off in
mice with laser light - cells which produce
dopamine in brain were affected by light
Daughters whose mom’s had higher stress in
their early life had more cortisol, and 14 years
later, there is a reduced connection between
amygdala and prefrontal cortex (Science News, 12/15/12,
p.10)
Example: Angiostatin
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Peptide which mediates thirst
Drop of angiostatin in rat’s brain will make rat
drink
Drop in LU or KI will also cause them to
conserve water: less water vapor exhaled, less
water in urine
All mediated by the emotion/drive state of “thirst”
More research:
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Birth weights are affected by economic
uncertainty
Poor sleep might be linked to obesity and
diabetes: lack of sleep hurts the ability of fat
cells to respond to insulin efficiently, spilling
lipids into bloodstream - a state associated with
metabolic syndrome, a precursor to Type 2
diabetes
Losing weight reduces inflammatory cells and
proteins in body, a risk factor for many cancers
Research on Pain
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Chronic pain can cause atrophy in areas
of brain involved with emotion, attention
and perception of danger. Meditation,
thoughts of a loved one, bio-feedback etc
caused less activity in somato-sensory
cortex, which plays role in perceiving pain
(Sean Mackey, pain management, Stanford u)
Exercise improves immune
response
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Helps fight off bacterial and viral infections
Decreases chance of developing heart
disease, osteoporosis and cancer
May help by flushing bacteria out from
lungs, flushing carcinogens out in urine
and sweat
Exercise send antibodies and wbc thru
body at quicker rate
Exercise cont’d
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Temporary rise in body temp may prevent
bacterial growth (similar to fever)
Slows down release of stress-related
hormones
Psycho-neuro-endo love
connection
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Lust: testosterone and estrogen surge
Attraction:
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Dopamine responsible for feelings of euphoria
Noradrenaline causes racy hearts and sweaty palms
Seratonin regulates body temp, mood and pain. Low
levels lead to obsessive thinking
Attachment:
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Oxytocin “love hormone” involved in bonding
Vasopressin encourages bonding
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Latest research
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Three new studies show that lab-produced
antibodies that target specific proteins in
cells can reduce LDL cholesterol at a rate
comparable to statins, without the side
effects
“A major conceptual shift in neuroscience has been
wrought by the realization that brain function is modulated
by numerous chemicals in addition to classic
neurotransmitters. Many of these informational substances
are neuropeptides, originally studied in other contexts as
hormones, gut peptides, or growth factors. …We now
realize that their signal specificity resides in receptors
rather than the close juxtaposition occurring at classical
synapses…. [we see neuropeptide receptors at brain loci,
on mobile cells of the immune system]… Neuropeptides
and their receptors thus join the brain, glands, and immune
system in a network of communication between brain and
body, probably representing the biochemical substrate of
emotion.
Candace Pert
Some additional thoughts
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We have been exploring the biological
basis for emotions/behaviors, but there
are many influencing factors:
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Genetic makeup
Environment (pre and post heaven)
Choices that we make
Important that we not think in small boxes
Speculations
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Could the intricate array of electrical and
chemical routes of communication of the
immune response lead to a memory of
illness within cells/
Is there a potential for memory in every
living cell?
To see a world in a grain of
sand, / And a heaven in a
wild flower, / Hold infinity in
the palm of your hand, / And
eternity in an hour.’
William Blake
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