The Biology Behind Stress

The concept of stress is universally known: high tension, sweating, fear, shock, etc. Stress in itself can be broken into biological, psychodynamic, behavioral, cognitive, and humanistic. In this article, we will look at the biological aspect behind stress: what is the biological story behind stress that causes this mechanism? How can we use this biology to improve stress?

Introduction

The brain is the central organ of stress as it stores memories, regulates behaviors and other psychological processes, and determines which occurrences should be considered threatening. Through the use of the hypothalamic-pituitary-adrenal axis, the autonomic nervous system, allostasis, and the immune defense system, exposure to multiple stressors can create a release of hormones that create the feeling of modern depression and anxiety.

Allostasis:

Allostasis is the active process of adapting to stressors through mediators such as cortisol and the autonomic, metabolic, and immune systems that act together in a non-linear fashion to maintain homeostasis. Allostatic (allostasis overload) itself refers to the accumulation of many stressors which can lead to the deregulation of the network allostasis leading to stress. Adaptations to this stress can be things such as taking time off work, spending time with family, or just hanging out with friends. However, maladaptations such as smoking, drinking, drugs, and violence can also be a form of a coping mechanism.

Within this allostasis, here is a list of the necessary molecules that take place in this whole allostatic process.

• BDNF - Brain-derived neurotrophic factor

  • Facilitator of plasticity or growth

  • Helps terminate effects of chronic stress

  • Helps prevent stress-induced plasticity

• tPA - Tissue plasminogen activator

  • Secreted signaling molecule and protease

  • required for stress-induced spine loss in hippocampus and medial amygdala

  • required for acute stress-induced increase in anxiety; CRF activates tPA secretion

  • CRF in amygdala regulates tPA release

• CRF - Corticotropin releasing factor

  • Created in the hippocampus through interneurons

  • Regulates thin spines through RhoA signaling

• Lipocalin-2 - secreted protein

  • Acute stress stops this protein

  • Regulates mushroom spines

  • Increases neural excitability and anxiety

• eCB - Endocannabinoids

  • Induced through glucocorticoids

  • Regulates emotions and HPA habituation

  • CB1 receptor KO increases anxiety and basolateral amygdala dendrite length and causes stress-like retraction of prefrontal cortical dendrites, likely through the regulation of glutamatergic transmission

  • Fatty acid aminohydrolase (FAAH) is a key regulator of eCB action

U-dosed Response Cycle:

There are many complex nonlinear interactions between various molecules in the biological aspect of stress that are central to allostasis. This relationship can be described through the inverted U-dose response cycle below:

Gene regulation:

Stress-altering gene expressions occur through myriad mechanisms, including the hormonal molecules mentioned above in Figure 1. These mediators span influences from extracellular adhesion molecules, to cytoskeletal elements, and at least one nuclear pore complex protein.

Overview of stress effects upon the hippocampus, amygdala, and prefrontal cortex:

The trio of brain regions discussed in the text and depicted in the figures have played a crucial role in advancing our understanding of cellular and molecular mechanisms, along with various cellular processes. This exploration has unveiled distinctive specializations in different brain regions, while also shedding light on shared mediators, intricate mechanisms, and the multifaceted interactions among these mediators.

Conclusion:

As previously stated, the general symptoms of stress are commonly known, and most individuals tend to seek help from a professional. However, it is also important to understand the biological aspects behind stress to gain a better perception and deeper insight into the causes of the problems. In this article, we looked at the very basics of biology on the aspects of allostasis, gene regulation, and effects on some parts of the mind. It is important to note that we have just scratched the surface of this field and there are many more articles to come that will cover this in depth! Stay tuned and subscribe.

Sources:

McEwen, Bruce S, et al. “Mechanisms of Stress in the Brain.” Nature Neuroscience, U.S. National Library of Medicine, Oct. 2015, www.ncbi.nlm.nih.gov/pmc/articles/PMC4933289/.

Overview of Abiotic Stress-Mediated Gene Regulation in Plants. This ..., www.researchgate.net/figure/Overview-of-abiotic-stress-mediated-gene-regulation-in-plants-This-figure-depicts_fig1_352669640. Accessed 25 Dec. 2023.