Crowding Stress

Peter Csermely

Crowding Stress: Psychosocial Effects,  Physiological Changes in Crowding Stress,  Possible Molecular Mechanisms of Crowding Stress,  Crowding of worms,  Molecular Crowding

amyloidosis a severe pathological change of various organs and tissues, where aggregated amyloid fibers develop and induce the destruction of affected cells.

channeling interaction of enzymes catalyzing consecutive enzyme reactions, where the product of the “first” reaction becomes the substrate of the “second” enzyme by a directed molecular transfer largely avoiding free diffusion.

hypothalamic-pituitary-adrenal (HPA) stimulation/axis a major peripheral mechanism of the stress response, involving three major constituents: the corticotrophin releasing hormone (CRH), corticotrophin (ACTH) and glucocorticoids.

molecular crowding a term to denote a dense population of molecules (usually: macromolecules), where aggregation, diffusion, hydration and other properties of the individual molecules are significantly altered.

Crowding stress is a type of psychosocial stress induced by an increased density of population. Population density may be raised either by increasing the number of species living in the same area and/or by reducing their living space. Crowding stress induces complex changes at the behavioral, physiological and molecular level, which differ, if crowding stress is acute, or chronic. Crowding stress can also be interpreted at the molecular level: molecular crowding promotes aggregation of various macromolecules and causes profound changes in numerous physico-chemical parameters of their solution.

I. Introduction

As outlined in the defining paragraph, studies on crowding stress face by an exceptionally high number of variables. Several consequences of crowding stress may differ greatly, if population density is raised by increasing the number of species living in the same area, or by reducing their living space. If crowding is increased to such an extent that it already leads to confinement, malnutrition, or an increased incidence of infections occurs, other complications develop. Crowding stress may be “acute” (transient), when the effects are studied after a few days, or “chronic”, when changes are investigated after prolonged overcrowding lasting for weeks, months, or even years. While mice or rats are the most commonly used species in crowding stress experiments, studies have been performed with almost all types of domesticated animals, various fishes and, last but not least, humans. Though the conclusions of these studies can be directly compared only within the same strain, some general trends can also be observed. The following Sections will focus on these general aspects of crowding stress.

II. Crowding Stress: Psychosocial Effects

Crowding as a chronic source of stress, constitutes a major threat to psychological well-being. Dense populations are characterized by considerably increased aggressive behavior. Crowded monkeys (even well-fed) have brutal fights, wound and kill each other, including females and young. Crowding stress adversely affects gonadal functions, and during pregnancy may inhibit reproductive activity even through the second generation (Marchlewska-Koj, 1997), among others by masculinization of female pups. Chronic crowding leads to deficits in learning tasks (Goeckner et al., 1973) and has been suggested as a stressor to induce an animal depression model (Naitoh et al., 1992). In human populations crowding stress is suggested as an important factor in the development of increased urban insanity/schizophrenia.

III. Physiological Changes in Crowding Stress

Crowding stress (especially if chronic) suppresses immune functions. Disturbed immune regulation leads to increased autoantibody levels and may be one of the factors behind the increased occurrence of childhood asthma (Kaplan and Mascie-Taylor, 1985) in crowded environment. Various infections are more likely to occur under crowded conditions. To enhance this effect even further, due to their suppressed immune system stressed species became more sensitive to infections and poisoning. As a widely established example household overcrowding has been related to an increased prevalence of Heliobacter pylori infections (Galpin et al., 1992).

Heliobacter pylori infections and crowding stress-induced gastric lesions significantly contribute to the development of ulcer and stomach cancer (Barker et al., 1990). Due to digestive problems and occasional appetite loss chronic stress induces a reduction in weight gain. In several organs, such as in kidneys and adrenals chronic crowding stress induces intensive amyloidosis. Chronic overcrowding in many cases leads to hypertension in resting state, or to “relative hypertension” after exercise.

IV. Possible Molecular Mechanisms of Crowding Stress

As one of the probable molecular mechanisms behind the above physiological changes crowding stress considerably impairs central histamine-, noradrenaline- and vasopressin- but does not change the corticotrophin-releasing hormone(CRH)-system involved in the hypothalamic-pituitary-adrenocortical (HPA) stimulation (Bugajski et al, 1995). As a possible result of the relative overweight of CRH/HPA stimulation appetite decreases, and in long term weight loss develops. HPA stimulation leads to compromised immune function and suppression of gonadal functions. Chronic HPA stimulation may lead to osteoporosis, chronic gastrointestinal pain and retarded growth (Csermely, 1998). Thus prolonged activation of the hypothalamic-pituitary-adrenocortical axis may explain many of the psychological/physiological symptoms developed by chronic overcrowding, such as gastrointestinal problems, weight loss, sensitivity to infections and decreased reproductive activity.

Crowding stress may impair cellular signaling mechanisms, such as changes in intracellular calcium levels especially in aged subjects (Csermely et al., 1995). Impaired signaling may significantly contribute to immune suppression and decreased adaptive mechanisms after chronic crowding stress.

Crowding of worms

The signaling mechanisms of crowding can be studied more easily in simple organisms. The fruit fly Drosophila melanogaster stops development in overcrowded cultures. Food limitation and overcrowding also induces an arrest in the development of the worm Caenorhabditis elegans leading to the formation of the so-called “dauer larva”. Daf-7, a homologue of the human transforming growth factor beta (TGF-beta) prevents dauer larva commitment (Ren et al., 1996), while several other members of the dauer larva regulating Daf-family are receptor serine-threonine kinases similar to the human TGF-beta receptor. Mutations of another overcrowd signaling pathway of C. elegans may quadruple the adult lifetime of the worm besides disturbing its dauer larva development (Larsen et al., 1995). Thus disturbances in crowding stress signaling may have profound consequences in the longevity of (simpler) organisms.

VI. Molecular Crowding

Crowding induces changes in the “behavior” of macromolecules as well. If the total volume of macromolecular species occupies a significant fraction of the total volume of the solution we refer to such a medium as “crowded” (Zimmerman and Minton, 1993). Molecular crowding induces an increased association of macromolecules enhancing channeling between enzymes catalyzing consecutive enzyme reactions, or improving signaling efficiency in organized signaling cascades (Rohwer et al., 1998).

Under experimental conditions molecular crowding is induced by polyethylene-glycol, or by dextrane. However, intracellular environment, where the total amount of macromolecules usually occupies more than 1/3 of the total volume, is a typical example of molecular crowding. At such high density macromolecules begin to compete for water molecules, their hydration becomes compromised, and consecutively osmotic stress occurs. The large amount of macromolecules and their immobilized hydrate shell represents a large “excluded volume”, which requires significant adjustments in physico-chemical description of the kinetics and equilibrium of various intracellular processes (Zimmerman and Minton, 1993).