Stress and the Brain: Part 1 of 3: The Stress Response

When the brain detects any kind of threat or stress, it sets a coordinated system into motion to counter the stress.  This is the stress response, and it involves autonomic, neuroendocrine, metabolic and immune components.  One of the most studied stress systems is the HPA (hypothalamic-pituitary-adrenal) axis.  To start off this component of the stress response, neurons in the hypothalamus release CRH (corticotrophin releasing hormone).  This then causes the pituitary gland to release ACTH (adrenocorticotropic hormone) into the circulatory system.  ACTH travels in the blood to the adrenal glands, which sit just above the kidneys, causing them to release glucocorticoids such as cortisol into the circulatory system. 

                Back in the brain, in an area called the hippocampus, there are receptors for these glucocorticoids, unsurprisingly called glucocorticoid receptors (GRs).  Once the stress has disappeared, glucocorticoids are supposed to bind to these receptors, which then function to shut down the hypothalamus, pituitary gland and ultimately the adrenal glands, putting an end to the stress response and returning the body to homeostasis.  Unfortunately, this system can go awry with chronic or particularly severe stress. 

Prenatal/Infant Stress and the Brain (check out my next 2 posts for Adolescent Stress and the Brain, as well as Stress and the Aging Brain)

            When pregnant moms-to-be are stressed, some of their glucocorticoids pass through the placental barrier and reach the fetus.  A certain level of glucocorticoids is required for proper nervous system development since they remodel the axons and dendrites of neurons and affect cell survival.  However, high levels of glucocorticoids have negative effects on brain development and later functioning.  Rats exposed to prenatal glucocorticoids have fewer receptors in the hippocampus later in life.  As I said before, these GRs function to shut down the stress response.  So if there are fewer GRs present in the hippocampus, the stress response is not shut down as effectively, leading to higher than normal levels of glucocorticoid activity later on (more on why this is important in the section on Stress and the Aging Brain). 

Higher prenatal glucocorticoid levels have three main effects on adult behaviour: learning impairments, greater sensitivity to drugs of abuse and increased anxiety and depression.  The learning impairments in particular are thought to be caused by the changes in the hippocampus, while drug sensitivity and anxiety/depression are thought to be caused by changes in the amygdala. 

In infancy and early childhood, the brain is surprisingly hyposensitive to stress.  Certain things can still affect brain development, however.  Good parenting actually results in a small decrease in the stress response to everyday occurrences (which is a good thing).  However, in cases of extreme deprivation, the HPA axis becomes seriously underactive, possibly due to a downregulation in the pituitary.  Basically, the hypothalamus releases so much CRH that the pituitary can't handle it anymore and gives up trying.  Remember that a certain level of HPA activity is needed in order for neurons to develop properly.  Luckily, this severe reduction in HPA activity can be fixed after a mere 10 weeks of proper care.   

Stay tuned for Parts 2 & 3!

Cristina McHenry

Concordia University

Adapted from "Effects of Stress Throughout the Lifespan on the Brain, Behaviour and Cognition" by Sonia Lupien et al. and inspired by Wayne Brake's Neuropharmacology course at Concordia University.