HPA-axis Flashcards
The HPA-axis pathway and affects in depression
Hypothalamus releases corticotrophin-releasing hormone (CRH) onto the anterior pituitary, which releases Adrenocorticotropic hormone (ACTH) onto the adrenal cortex, which then releases cortisol. Cortisol can then do negative feedback on the hypothalamus and the anterior pituitary
Increased cortisol in depression, and increased CRH. Growth in size of the pituitary and adrenal glands. Negative feedback of cortisol impaired.
Adrenal glands function, location and activation
Located on the top of the kidneys. Produce glucocorticoids like cortisol, and mineralocorticoids like aldosterone. Also produces catecholamines like NA and adrenal to release into the blood.
Activated by the sympathetic nervous system.
The mediator of what activated the adrenal gland determines what will be released, e.g., ACTH releasing cortisol, SNS releasing adrenaline.
Cortisol will increase metabolism, lipolysis, protein breakdown, glycogenesis, and will be immunosuppressant.
Circadian and ultradian rhythm and the adrenal glands.
The suprachiasmatic nucleus (SCN) is the pacemaker of the circadian rhythm, affected by light changes. Innervates the adrenal glands, to rhythmically produce glucocorticoids.
Will cause cortisol to peak in the morning for the metabolic demand of the day.
Circadian mutations will consequently delay cortisol rise (will be reactionary as opposed to anticipating).
Episodic increases of cortisol will occur several times throughout the day. known as the ultradian rhythm. mainly due to hormones. facilitates the regulation of glutamate transmission and hippocampal LTP.
Acute stress from cortisol and problems from chronic activation
Beneficial in short term for survival and increased attention. increases cortisol and ACTH
E.g., flight or fight response.
Increases to anxiogenic (anxiety) behaviours, arousal (insomnia), scanning attention, and memory. Sees decreases in glutamate function, immune function, and reproductive function.
In chronic activation causes anxiety, insomnia, attention disruption, memory loss, increased risk of cardiovascular disease, increased infection risk, sexual disorders, GI problems, etc…
Mechanism of glucocorticoids and mineralocorticoids
Act at GR and MR respectively.
MR is occupied at low (basal)[cortisol] due to high affinity, while GR is occupied at high (stress situations) [cortisol] due to lower affinity.
Neurobiology of cortisol activation in AD
Locus coeruleus found to degenerate in AD. It is the primary source of NA.
Acute stress in mice models was found to increase locus coeruleus activity and induces anxiety-like behaviours.
Chronic activation was found to alter gene expression, increasing the production and secretion of amyloid-B proteins. This mechanism occurs by the internalisation of amyloid precursor protein (APP), which will be cleaved by B- and Y- secretaries in the IC endosomes.
The heightened activation of B2-ARs can lead to stimulation of y-secretase, increasing B-amyloid plaque formation.
effects and characteristics of Desensitisation of NA-mediated astoglia functions
Following chronic hyperactivity of the locus coeruleus, desensitisation of the NA mediated astroglia functions can occur. Under normal conditions they are antiinflammatory, clear amyloid-Beta, and aid in metabolism. Desensitisation can lead to accumulation of amyloid-B - increases AD risk.
Also leads to chronic neuroinflammation - associated with a wide range of disease pathologies.
The neuroinflammation and reduction of antioxidant abilities associated with this desensitisation can also present itself in Parkinsonism.
