Test 2 Flashcards
Function of endocrine system
To mediate bodily processes (balance and homeostasis)
Hormone
A chemical released by a cell or gland in response to external or internal signals, which travels to a distal site where it affects other cells.
Endocrine hormone
Hormone released into the bloodstream
Exocrine hormone
Hormone secreted into a duct and then into blood or from cell to cell via diffusion (paracrine signalling)
Autocrine signalling
When hormone stimulates the very cell that released it
Steroid hormones
Includes corticoid and sex hormones
Glucocorticoids
Class of steroid hormones that bind to glucocorticoid receptors
Peptide hormones
Hormones made up of amino acid chains. These include vasopressin, growth hormone, insulin, ghrelin, etc.
How do you assess the relationship between a hormone and behaviour in mice?
Assessed with KO mice/ blocking specific receptor/ surgery to reduce hormone naturally and examine the consequences. You can then give the mouse hormone replacements to see if that reverses the effects
Assessing the relationship between hormones and behaviour in humans
- We can assess individuals with diseases that involve hormone disruption.
- We can assess individual differences of hormone levels
- We can determine whether a variant of a gene is associated with a decrease in levels of hormone/disturbances of a hormone receptor and then relate that to a behaviour.
Describe the HPA axis
1) Stress activates hippocampus or activates the amygdala which in turn activates the hypothalamus
2) Hypothalamus activation results in CRH and AVP release
3) CRH stimulates ACTH release from the anterior part of the pituitary gland. ACTH is then released into the bloodstream
4) ACTH reaches the adrenal glands (located on top of kidneys) and stimulates cortisol release.
5) Cortisol affects its many targets: muscles, adipose tissue, pancreas and regions of the brain (hypothalamus and hippocampus).
6) When cortisol reaches the brain, it regulates the system by inhibiting its release of CRH and effectively stopping the stress response.
Impacts of cortisol
- Increase blood sugar through breakdown of glucose in liver and muscle
- Metabolize fats, carbs and proteins
- Limits overactivation of the immune response
What do mineral corticoids do?
They stimulate active NA+ reabsorption and passive water reabsorption, thus increasing blood volume and blood pressure.
How does the body cope with chronic stress/activation of the HPA axis
Through various adaptations which occur in response to a chronic stressor so that the cortisol response is less pronounced.
Do adaptations occur slow or fast if the chronic stressor is the same on every account?
It occurs fast.
Do adaptations occur slow or fast if the chronic stressor is intermittent/unpredictable?
It occurs slow.
Is adaptation event specific or occurs generally?
Adaptions are seen to be event/cue specific. If a novel stressor is introduced, a normal stress response ensues.
What are some of the downfalls to adaptations in response to chronic stress?
- After stress, vulnerability to common cold in increased.
- Inflammation from down-regulated receptors can contribute to development of diseases such as type 2 diabetes or heart disease.
Prenatal stressor events effect on offspring
Stressing a pregnant rat increases the level of corticosterone in the rat and the fetus. This can result in many biological cascades, like change in strux of stress-sensitive brain regions. This can in-turn lead to various pathologies in the offspring such as attention and learning deficits, increased chance of anxiety depression and schizo.
How do previous stressful experiences effect the HPA axis?
HPA functioning seems to be downregulated in individuals who have encountered previous abuse/trauma. This makes sense because if HPA axis was exaggerated at every aversive stimuli, then the system would encounter allostatic overload.
How is CRH implicated in more than the HPA response
- It could promote 5HT release through the regulation of neurons in the raphe nucleus.
- Could increase forebrain norepinephrine release through infusion in the locus coeruleus.
Fear
A directed emotion that is elicited in response to stimuli that have been paired with an aversive stimuli
Anxiety
Elicited by diffuse stimuli (general environmental context) or it can reflect a free-floating emotion, or one that is felt in anticipation of a threatening event.
What part of the amygdala do systemic stressors influence?
They influence central amygdala activity
What part of the amygdala do psychogenic stressors influence?
They influence medial amygdala activity
What part of the amygdala do fear eliciting stimuli increase CRH?
Increased CRH at various regions INSIDE the amygdala
What part of the amygdala do anxiety eliciting stimuli increase CRH?
Increase CRH in the outer regions of the amygdala specifically the Bed Nucleus of the Stria Terminalis (BNST)
Bed nucleus of stria terminalis
- Output pathway that runs from the amygdala to the hypothalamus
- Neurons in this region are important in governing responses to spatially or temporally distant challenges.
CRH receptor subtypes
CRH1 and CRH2
Leptin
Hormone that reduces food intake.
- It is produced by adipocytes and can influence HPA axis activity.
- Influences the release of some NTs (DA, 5HT) which in turn affects reward seeking behaviours (in terms of food).
Ghrelin
Hormone that increases food intake (as well as neuropeptide Y).
- Levels increase before mealtime
- Stimulates orexin (food craving hormone).
Bombesin (BB)/Neuromedin B(NMB) and gastrin
Release peptide (GRP) act as satiety signals (to reduce food intake)
Insulin
Regulates fat and carb metabolism
- Takes glucose from blood and stores as glycogen inside of tissues.
- Inhibits NPY release which decreases food intake.
Eating hormones implication in stress
- Depressive like behavioural disturbances provoked by chronic stressor could be antagonized by leptin administration
- BB-like peptides can promote anxiety, BB receptor antagonist had the opposite effect.
- Following sufficiently protracted stressor experience, effectiveness of insulin could be decreased.
Sex hormones and stress
- Estradiol (estrogen) can act as a brake on the HPA axis
- Progesterone may result in disturbed negative glucocorticoid feedback.
Effect of chronic cortisol on brain
It can increase signals in the amygdala and decrease function of the hippocampus. The hippocampus is responsible for turning off the HPA axis so this can result in decrease ability to control stressful situations.
As stress increases, hunger ________
decreases.
What is the CRH1 receptor associated with?
The CRH1 receptor is associated with anxiety, primarily affects the psychological aspects of anxiety
What is the CRH2 receptor associated with?
It is also associated with anxiety but tend to be associated with the physiological aspects of anxiety such as increased heart rate, respiration, pupil dilation, etc.
Explain 2 instances where certain characteristics are both advantageous and disadvantageous.
1) Sickle cell anemia is a disease where the blood cells are sickle shape, resulting in decreased oxygen carry. Having this disease/gene for the disease in Western world is a great disadvantage. IN Africa, it is quite advantageous to have a gene for this disease because these individuals are not affected by malaria/do not get malaria.
2) Norepinephrine is a neurotransmitter implicated in the sympathetic nervous system response fight or flight. IF you are in a scenario where you are being chased by a bear, NE pumping through your body is advantageous as it gives you the means to either fight or flight. Lots of NE activation can be disadvantageous because it can cause cardiac problems in the future.
Oxytocin and women
Women have “tend and befriend” characteristics which are attributed to their levels of oxytocin.
Oxytocin and men
They have a tend and defend characteristic. Typically males have parochial altruism (basic altruism) compared to women.
Robyn McQuaid’s data on Oxytocin
Oxytocin seems to change our sensitivity to different stimuli. Levels of oxytocin can be implicated in bonding behaviour, where the bond itself is not increasing but rather the high levels of oxytocin represent a sensitivity to what the other being is feeling. The opposite is true in which if oxytocin is high when encountering a negative stimuli, you will be more sensitive to feel negatively towards that event.
Characteristics of neurotransmission
Neurotransmitters are released into the synaptic cleft. Many of these NTs enter into the post synaptic cell via their receptors. A portion of these NTs that get released do not make it into the post-synaptic cell but rather go back to the pre-synaptic cell to signal a stop on NT synthesis and release. The more time that NTs are in the synaptic cleft the larger chance that most of those NTs will go into post-synaptic cell, this is important when creating treatments for pathologies
Enzymatic degradation
Break down of a NT via enzyme
Reuptake
When NT is brought back to pre-synaptic cell to be degraded and reassembled into a new NT
Serotonin
A monoamine implicated in sleep, immune function, mood regulation.
Where does serotonin mostly reside?
Found mostly in the gut. used to pass messages from the gut to the brain. Serotonin does not enter the brain directly as it is too big but sends messages through other chemical cascades (activation of the vagal nerve).
Dopamine
A monoamine that is implicated in reward, pleasure and motivation. Precursor molecule L-Dopa is used to treat the symptoms of Parkinson’s disease
Agonist
Drug that stimulates a specific receptor directly
Antagonist
Drug that blocks the receptor.
Acetylcholine
Implicated in the parasympathetic portion of the NS.
How is acetylcholine implicated in poisonous gas?
Acetylcholine is normally broken down by acetylcholinesterase. If this enzyme is not functioning, acetylcholine will build up in the body having poisonous effects subsequently killing the individual. In both world wars, this information was used as a method to create poisonous gases.
Exs: Atropine (used at eye doctor as pupil drops), Scopolamine (thought to be a truth serum in WW1 - also can be used as a date rape drug as it gets rid of your inhibitions)
Neurotransmission under normal conditions
NTs are stored in the presynaptic cell - a certain amount is synthesized and utilized, equal to one another.
Neurotransmission under acute mild stress
NT functioning is increased –> synthesizing and utilizing more than normal, still equal to one another
Neurotransmission under acute severe stress
NT is being more utilized that synthesized, therefore balance is not equal. Under this condition, you are more vulnerable to certain behaviours (mood changes,etc) and this is also a sensitizing effect that if you are encountered with a similar stressor in the future your body will react larger and faster.
Neurotransmission under chronic stressor
Synthesis of NT is higher than utilization. This is a safety mechanism because your body is used to using many NTs to get rid of the daily stressors. The auto-receptors on the pre-synaptic cell is blocked, therefore there is no feedback loop to stop synthesis.
Neurotransmission and allostatic overload
Synthesis and utilization are severely increased.
GABA
Most abundant inhibitory NT
GABA receptor
Has 5 components, at the center of the components is a channel. There are three subtypes of components: beta, alpha and gamma. Depending on the combination of these subtypes in the specific receptor will allow different things to act on the receptor.
Glutamate
Most prevalent excitatory NT associated with anxiety, hyperactivity, impulsivity, night waking’s, movement and motor control, release of adrenaline.
Describe how glutamate can have a neurotoxic effect
Following an ischemic stroke, shortly after the patient will seem to be fine. After days, the patient will typically get progressively worse because the CNS immune system is overexaggerated and subsequently killing neurons. You will find a major glutamatergic reaction/release which causes surrounding neurons to die.
The method of NT release in the endocannabinoid system.
Neurotransmitters stimulate the post-synaptic neuron. This results in endocannabinoid release from the post-synaptic cell to activate the pre-synaptic Cb1/Cb2 receptors.
Two types of cannabis receptors
Cb1 - most in the brain.
Cb2 - mostly in the periphery but also in the brain.
BDNF
Growth factor that increases synaptic plasticity and neurogenesis. Certain illnesses are accompanied by decreased amounts of growth factors - therefore synaptic connections are not as made easily.
Basic fibrosis growth factor (FGF-2)
Similar to BDNF, contributes to cell proliferation, differentiation and cell survival (especially in hippocampus).
How does stress impact FGF-2
- Acute stressor = small decrease
- Chronic stressor = huge decrease
- ability to control the stressor seems to be more implicated in shift of FGF levels
- injecting FGF in the brain has shown to alleviate depressive symptoms in mouse models.
How do immune cells communicate and multiply - give an example.
Immune cells communicate via cytokines which activates cascades to initiate proliferation of our adaptive immune cells.
For example: Macrophages and dendritic cells release cytokines which activate Th1. Th1 releases cytokines to activate the Cd8+ cytotoxic t cells/also causing them to multiply. Th1 also releases cytokines to turn on the B cells. T17 cells activate our Treg cells which shuts down the Th1 pathway - reducing cell death and inflammation.
Anti-inflammatory cytokines
IL4, IL10 - produced by Th2 cells
Pro-inflammatory cytokines
IL1, IL6, TNFalpha - produced by macrophages and Th1 cells
What do natural killer cells preferentially attack?
Viruses.
Is T cell method of killing a direct or indirect method?
Direct
Is B cell method of killing a direct or indirect method?
Indirect because it recruits the complement system to kill the pathogen.
Endogenous cortisol sets a ______ on the actions of cytokines
a maximum/a cap
Microbiota
Different parts of our body (skin, gut**, nasal cavity, mouth, private parts) are filled with microbes - some commensal bacteria (good), some bad. They are in a balance with one another.
Dysbiosis
When there is an unbalance between good and bad microbes.
Eubiosis
Harmony between commensal and harmful bacteria.
How is the individual affected when dysbiosis occurs?
The individual becomes more vulnerable to pathologies/illnesses. Viral particles can reach the intestine, then escape and activate inflammation in the brain via the vagal nerve.
C-reactive protein (CRP)
Protein released from the liver whenever there is inflammation in the body that is too high.
Sterile inflammation
When immune system is activated by something other than a pathogen (stress, toxins)
Glymphatic system
Gets rid of garbage.
Immune system
System that protects us from all manner of foreign microscopic invaders.
Innate immune cells
Mainly myeloid cells (cells that come from bone marrow) such as neutrophils, monocytes, macrophages and dendritic cells.
Natural killer cells
They surveil the area and cells in the area. If the surrounding cells have a certain marker, the NK cells will not initiate a response. If the cells DO NOT have a certain marker, the NK cells will initiate an immune response.
Adaptive immunity
Consists of lymphoid cells that respond to a specific single antigen: T and B cells.
B cells
- Neutralize foreign bodies traveling in the individual.
- Termed humoral response bcuz the B cells produce antibodies/immunoglobin molecules which appear within bodily fluids (humorals)
B memory cells
Can survive for years in the body and can recognize an antigen faster and initiate a quicker immune response
B antibody producing cells
Secrete soluble antibodies to get rid of pathogens
T cells
Referred to as cellular immunity because they evolved to attack cells infected by pathogen.
Cytotoxic t cells (CD8+)
Cause apoptosis on pathogen infected cells
T helper cells (CD4+)
Information couriers that direct and stimulate actions of other immune cells.
Immune tolerance
Down regulation of immune cells in order to limit risk of autoimmunity.
T regulatory cells
Part of the inhibitory immune response as they inhibit CD8+ cells from attacking self tissue.
Cytokines
Immune chemical messengers.
Chemokines
Comprise several families of small cytokines that attract immune cells through their chemo attractant capacity to sites of tissue infection and inflammation.
Inflammasomes
Immune sensors involved in the promotion of inflammation in response to infection.
Microglia
Macrophages of CNS, also implicated in synaptic pruning, neurogenesis, and memory formation
Implication of glucocorticoids in the immune response
They can be activated by inflammatory immune stimuli. They act as a immunosuppressant. Except when faced with a chronic stressor, they may be downregulated therefore their immunoresponse may be diminished.
Does stress tend to shift cytokines to mostly anti-inflammatory or pro-inflammatory?
You see an increase of pro-inflammatory cytokines following a stressor.