Lecture 2 -Neuroendocrinology II Flashcards
What is POMC?
Poopiomelanocortin is the pre-pro protein of ACTH and opiod peptides
Where are the adrenal glands located?
Atom the kidney and are based in fatty tissue
Which germ layer did the adrenal cortex stem from?
Mesoderm
Which germ layer did the adrenal medulla stem from?
the neuroderm
What is aldosterone important for?
Iron metabolism and facilitates na reabsorption
Outline the HPA axis
Hypothalamus –> (CRH)–>Adenohypophysis –>(ACTH)–> Adrenal Medulla –> (Corticosterone and Cortisol) –> Blood
There is also nerve innervation to the medulla coming from the sympathetic nervous system –> stress hormone production
How can the stress response be measured?
By measuring blood concentrations of ACTH and corticosterone
What is the stress response dependent upon?
Quality of the stressor
Physiological Adaptations
Pathophysiological response
What are the key behavioural adaptations peripartum?
Maternal behaviour
Child attachment and bonding
Altered emotionality i.e. maternal aggression, increased calmness and reduced anxiety
What are the neuroendocrine adaptions peripartum?
Oestrogen/progesterone fluctuations
reduced resonsiveness of the HPA axis to stress
Increased activity of the oxytocin/prolactin system
What are the mechanisms involved in maternal stress?
- Perception of the stressor - reduced fos expression in limbic brain regions
- Reduction in excitatory inputs to the PVN
- Inhibitory action of the relevant neuropeptides
- Reduction of the CRh system activity
What are the two main functions of maternal stress?
to protect the baby against excessive levels of glucocorticoids
to balance the massive fluctuations in sexual steroids peripartum therefore being essential for maternal mental health
What can severe stress during pregnancy cause?
Prevent adaptations to the CRH system thus creating post-partum depression
What are the groups of post-partum disorders?
Maternity Blues - common
The pure post-partum depression - no history of depression
Women with a preivous history of major/minor depression - post-partum episode =most sever experienced
Post-partum psychosis - agitation, pressured speech, hallucinations, delusions, confusions and sever sleep disturbances
What are the symptoms of non-psychotic post-partum depression?
Irritable, unhappy, anxious agitated, poor sleep and poor appetite
What is CRF?
A neuropeptide in the brain which is synthesised in the PVN, where it’s synthesis is increased after acute stress
What are the criteria for NPs in the brain?
Synthesis ReleaSE Receptors Receptor mediated action Behavioural relevane Pyshiological relevance
What are the pathophysiological adaptations of the CRF system in anxiety and depression?
Increased cortisol concentration in saliva
Increased cortisol
Lower plasma cortisol
Increased CRF in CSF
What does CRF do?
Promotes passive stress coping Reduces food intake increases anxiety increases arousal stimulates sympathoadrrenal output induces sleep disturbances alters immune functions inhibits sexual behaviour and reproductive functions
Describe an animal model for depression/anxiety
Use HAB rats
Test on an elevated plus maze
What happens when you trap mice on the outside arms of the elevated plus maze?
An increase in ACTH
What single nucletotide polymorphism occurs in HAB rats?
In the vasopression gene causing increased vasopressin productionW
What does the Dexamethasone-suppression/CRH challenge show in humans?
Pathological HPA axis hyperactivity
Involvement of endogenous AVp in depressed patients
Indicates pathological hyperactivity of AVP/CRH
What diseases can chronic stress help cause?
Fibromyalgia Chronic pain Cancer Bipolar disorder PtS Anxiety Depression IBD Rheumatoid arthritis Burn out syndrome asthma
Outline a new model for showing stress in animals
the Chronic subordinate colony housing, helps mimic human stress by creating social stress in rodents. They do this by having two male mice in a cage, the macho mouse is 5g heavier therefore always wins. The macho mousse is changed on days 8, 15 and 19 to create constant social defeat.
What are the consequences of chronic social defeat in rodents?
Reduced body weight gain Reduced thymus weight Increased adrenal weight Adrenal hypertrophy yet adrenal insufficiency HPA axis malfunction inflammation cellular immune functions long lasting anxiety increase impaired social behaviour reduced neurogenesis
How can early life stress affect adult stress?
It has an additive effect, so those that have early life stress are more likely to develop chronic social stress in adulthood, this can be pre or post-natal
What type of vasopressin do all mammals have?
Arginine Vasopressin (AVP)
What type of ‘vasopressin’ do all other vertebrates have?
Arginine Vasotocin (AVT)
What type of ‘Oxytocin’ do different animals have?
Mammals - Oxytocin
fish, amphibians, reptiles, birds and marsupials - Mosotocin
Some fish - Isotocin
What are the stimuli for central release of oxytocin?
Birth
Suckling
Stress
Sex
What are the stimuli for peripheral release of oxytocin?
Birth
Sucking
Stress
Sex
What are the stimuli for central release of vasopressin?
Stress
Maternal Behaviour
What are the stimuli for peripheral release of vasopressin?
Osmotic challenge
Blood loss
