Stress and the HPA Axis
What does chronic stress have to do with the hippocampus and memory? Quite a lot, it turns out. Let’s start with a look at why a healthy bodily response to stress is necessary for survival in all animals, including humans. Responding to stress allows us to adapt and change with our environment. Our bodies cannot stay in a relaxed state during stressful events, so upon encountering a stressor the brain sends signals to the rest of the body to get ready to fight or flee. The hypothalamus-pituitary-adrenal (HPA) axis is the brain’s control center for this reaction to stress. Norepinephrine, epinephrine, and cortisol are some of the main signals the body uses to initiate the fight-or-flight response. They redirect metabolism to the limbs, slow digestion, increase blood sugar and blood pressure, and provide energy for conquering or running from the stressful situation. Animals need this physiological change to happen in their bodies, as usually the stressor is a predator that would require huge amounts of energy to run from or fight. Humans, while eliciting a parallel physiological response to stress as other animals, do not usually need to actually run from or fight off a stressor. Our stressors are arguments, embarrassing social situations, deadlines at work, college course loads, and other situational factors we deal with daily. Although these stressors shouldn’t require us to prepare to sprint, our bodies still respond with a fight-or-flight activation of the HPA axis. Stress can cause a cascade of problems in humans due to this unnecessary redirection of metabolism and excitation. Cortisol is the most notorious of the stress hormones and over-secretion of it can cause problems throughout the entire body.
The HPA axis works in conjunction with many other areas of the brain and glands throughout the body. The hippocampus, located in the medial temporal lobe of the brain, is necessary for cognitive functions such as learning, memory, and regulation of behavior. It plays a key role in gathering and encoding information and then later retrieving that information. During times of stress, your brain needs to focus on sensory stimuli and quick problem-solving, so hippocampus function is altered. This is part of why upon unexpectedly seeing a romantic interest or giving a public speech we forget simple things like our address or what we had for breakfast. The hippocampus is less functional during times of both acute and chronic stress. There are corticosteroid (cortisol) receptors all over the hippocampus, which is why stress can so readily impede this part of the brain. The two important receptors to know are called MRs (mineralocorticoid receptors) and GRs (glucocorticoid receptors). MRs have a high affinity for cortisol and are bound to cortisol even when a stress response isn’t occurring, which is necessary for normal hippocampus function and flow of information. GRs have much less affinity for cortisol and are typically only activated when cortisol levels are high (when you are stressed). When GRs are activated, neuronal formation of new memories is suppressed. This balance of cortisol promoting information flow but hindering hippocampus function during times of stress is necessary for a healthy response to stress.
Memory and Damage to the Hippocampus
Chronic stress can cause long-term damage to the hippocampus. In fact, the hippocampus itself has been shown to shrink in size in people suffering from an ongoing HPA axis stress response. Nerve cells, the body’s way of conducting information and signals from one part to another, are typically highly branched or elongated. Stress causes reduced nerve branching and development and even causes nerve cell death in the hippocampus. Nerve cells are also less elongated in individuals with stressful lifestyles or who grew up in a stressful household. The GRs on the hippocampus become overactivated with ongoing stress, which prevents nerve cell excitation. The combination of hippocampus shrinkage, nerve cell damage, and overactivation of GRs causes an inability to retrieve and form memories. This explains why both short and long-term stress can cause memory lapses and poor focus. It is common for people to be incapable of recalling the details of a traumatic event, which is why it can be inconclusive to put victims of heinous crimes on trial or to ask a driver the details of a car wreck. Cortisol released during a stress response has also been shown to damage contextual memory, meaning memories may be formed but their context is ambiguous. For example, repeated stressful stimuli from a traumatic situation (such as combat) can cause severe anxiety and PTSD where one can recall and relive the general state of fear, but not the details of the situation that provoked fear. Stress in early childhood is also associated with diminished nerve function and reduced capacity for memorizing information. It is possible to restore hippocampus function and improve memory through lifestyle modifications and various restorative therapies for HPA axis balance. Adaptogens are herbal extracts which can muffle the effects of both overactive and underactive stress responses. Rhodiola is an example of an adaptogen shown to reduce cortisol levels and promote higher tolerance to stress. If you have trouble with memory, consider examining possible imbalances in your HPA axis, supplementing with adaptogens such as Rhodiola, Ashwagandha, or Tulsi, and addressing lifestyle factors that may be increasing your stress level.
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 Van Ast, V. A., Cornelisse, S., Marin, M.-F., Ackermann, S., Garfinkel, S., & Abercrombie, H. C. (2013). Modulatory mechanisms of cortisol effects on emotional learning and memory: Novel perspectives. Psychoneuroendocrinology, 38(9), 1874–1882. http://doi.org/10.1016/j.psyneuen.2013.06.012
 Joëls, M., Karst, H., Krugers, H. J., & Lucassen, P. J. (2007). Chronic stress: Implications for neuronal morphology, function and neurogenesis. Frontiers in Neuroendocrinology, 28(2-3), 72-96. doi:10.1016/j.yfrne.2007.04.001
 Joëls (2007), Ibid.
 Hanson JL, Chandra A, Wolfe BL, Pollak SD (2011) Association between Income and the Hippocampus. PLOS ONE 6(5): e18712. doi: 10.1371/journal.pone.0018712
 Züst MA, Colella P, Reber TP, Vuilleumier P, Hauf M, et al. (2015) Hippocampus Is Place of Interaction between Unconscious and Conscious Memories. PLOS ONE 10(3): e0122459. doi: 10.1371/journal.pone.0122459
 Abercrombie, H. C., Jahn, A. L., Davidson, R. J., Kern, S., Kirschbaum, C., & Halverson, J. (2011). Cortisol’s effects on hippocampal activation in depressed patients are related to alterations in memory formation. Journal of Psychiatric Research, 45(1), 15–23. http://doi.org/10.1016/j.jpsychires.2010.10.005
 Joëls (2009), op. cit.
 Joëls (2009), Ibid.
 Conrad, C. D., Mauldin-Jourdain, M. L., & Hobbs, R. J. (2001). Metyrapone Reveals That Previous Chronic Stress Differentially Impairs Hippocampal-dependent Memory. Stress (Amsterdam, Netherlands), 4(4), 305–318.
 Joëls (2007), op. cit.
 Conrad, op. cit.
 Joëls (2009), op. cit.
 Züst, op. cit.
 Van Ast, op. cit.
 Hanson, op. cit.
 Joëls (2007), op. cit.
 Ishaque, S., Shamseer, L., Bukutu, C., & Vohra, S. (2012). Rhodiola rosea for physical and mental fatigue: a systematic review. BMC Complementary and Alternative Medicine, 12, 70. http://doi.org/10.1186/1472-6882-12-70
 Ishaque, Ibid.
Disclaimer: The information provided is only intended to be general educational information to the public. It does not constitute medical advice. If you have specific questions about any medical matter or if you are suffering from any medical condition, you should consult your doctor or other professional healthcare provider.