Itt írjon a(z) stress_and_plasticity-ról/ről

Stress related plasticity of the hypothalamus

Sarah Clarke, Ciara O’Sullivan, Johanna Rood

1.0 Introduction

Stress initiates an immediate response of multiple neural and endocrine systems (Bains et al, 2015). Both humans and animals respond to environmental anxiety with a stress response that allows for an adaption to the stressor to maintain homeostasis (Sheng et al, 2020). The plasticity of the hypothalamus is its ability to change and adapt to new information and stressors. Recent studies suggest that stressful experiences leave indelible marks on the paraventricular nucleus (PVN) of the hypothalamus and alter the ability of their synapses to undergo plasticity (Bains et al, 2015). Dysregulation of the hypothalamic- pituitary-adrenal (HPA) axis has been related to a range of affective and stress related disorders (Levy and Tasker, 2012).

2.0 The Hypothalamus and its plasticity

The hypothalamus is located within the diencephalon of the brain along with the thalamus and consists of several subnuclei. It has a major role in regulating the autonomic nervous system (ANS), subdivided into the parasympathetic (PNS) and sympathetic nervous system (SNS) (Klein, 2013). The hypothalamus secretes hormones and sends numerous neural impulses signalling the hypophysis, commonly known as the pituitary gland. The hypophysis has a major role in maintaining homeostasis of many biological processes, for example controlling the cardiovascular system, fluid distribution and thermoregulation (Klein, 2013). Neural and hormonal signals are delivered to target tissue by the SNS and PNS division. Nerve impulses are usually rapid and have a short duration of action, in contrast the endocrine system relies on chemical messengers that will produce a slower end result but with often long-lasting effects (Aspinall, 2003).

• The HPA axis (see figure 1) is one such neuroendocrine mechanisms that mediates the effects of stressors by regulating many physiological processes such as immune responses, metabolism and the ANS. The HPA axis conveys a cascade of endocrine pathways that respond to communication with the hypothalamus, pituitary- and adrenal glands via a negative feedback loop (Sheng et al, 2020).

HPA axis

Figure 1 – The Hypothalamus-pituitary-adrenal axis

(used under CC)

Coticotrophin-releasing factor (CRF) is responsible for activating the HPA axis as part of the common stress response pathway. The release of this hormone is initiated by the PVN of the hypothalmus as a response to relevant stress signals and works via neuroplasticity related mechanisms. Meng et al (2018) suggest this includes such responses as changing the amount of glutamate released and regulating the number of glutamatergic synapses on CRF neurons.

• The hypothalamus retains forms of plasticity throughout life and immature synapses can frequently be found in the hypothalamus of the adult. The magnocellular system for example, shows plasticity during changes in water homeostasis. The hypothalmo-neurohypophysial system in the adult undergoes activity-dependant, reversible morphological changes which result in reduced astrocytic coverage of its neurons and an increase in their synaptic contacts (Dietrich and Hovath, 2005). In contrast Theodosis et al, 2004 suggest that recent observations show that neurons and glial cells of the hypothalmo-neurohypophysial system continue to express ‘embryonic’ molecular features which may conclude their ability and capacity to undergo plasticity.

  The studies of plasticity and predictive responses show that reprogramming occurs across almost all species. Morphological changes can occur due to a range of environmental cues, which can alter gene expression to help conform to recurring environmental pressures (DeWitt and Scheiner, 2004). Further research is needed to clearly determine how the plasticity of the hypothalamus is attained, however some stressors that can influence this have been established.

3.0 Stressors and the generalised stress response in the Hypothalamus

• Reser (2016) states that stressful situations are unpredictable and high-level cognition may be less effective during these times. In this case, the animal should increase its dependence on instinctual behaviours for survival that are controlled by the lower brain centres. Thus, confirming stress has an immediate effect on brain functionality and certain stressors will affect the brains morphology in many ways. Marino et al (2019) state that the brain is the organ determining what is a non-life threatening and life-threatening stress. The brain further orchestrates the behavioural and physical responses which could cause health promoting or health damaging effects. The brain changes in its architecture, molecular profile and neurochemistry under acute and chronic stress, directing many body systems such as the cardiovascular and immune system leaving short and long-term consequences of being “stressed out” and potentially becoming health damaging.

  Hormones released by the hypothalamus associated with chronic stress function to protect the body in the short term, promoting adaptation which should help overcome the stressor. However, if such a condition is not met the stressor will become permanent and the chronic stress response will initiate changes that may affect mood, memory, decision making and general health and wellbeing amongst others (McEwen, 2012). It has been found that desensitisation to stressors on a long-term basis decreases secretion of peripheral HPA (hypothalamic-pituitary-adrenal) hormones such as ACTH (Armario et al, 2004). Researchers have also found sufficient evidence to support the hypothesis that long term exposure to a certain stressor can decrease the response of central parts of the hypothalamic-pituitary-adrenal axis such as gene expression in the PVN in the hypothalamus (Armario et al, 2004).

• A review of studies by Lightman et al (2020) investigates if the stress response elicited by ACTH is dependent on a pulsating release of the hormone to prevent downregulation. ACTH will regulate the release of, amongst others, corticosterone from the adrenal gland. In rats where the adrenal gland had been removed, such animals receiving a constant exposure to corticosterone showed a significant impairment in the stress response compared to rats receiving corticosterone in physiological pulsatile doses. This confirms that even with part of the feedback mechanism removed, the hypothalamus can adapt to a certain degree but cannot always overcome certain stressors, ie. pathological changes or unrelenting environmental conditions.
  • Other than the generalised stress response, often stressors have specialised pathways in the brain. For the purposes of determining plasticity of the hypothalamus however, the authors of this paper will only highlight individual stress responses relating to nutritional, heat and transport stressors. It should be noted that stressors are often interrelated and can start a cascade of biological responses which can affect many regulatory systems. For instance, a general stress response will immediately initiate a lack of hunger.