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 EVOLUTION  AND  STRESS  RESPONSES  TO  CHANGES  IN  ENVIRONMENT

But environments do change, sometimes a lot, sometimes a little, daily, seasonally, yearly, and over longer, geological periods. And these changes are important. The heart of the evolutionary process lies within local ecosystems, for it is here that ecological and evolutionary processes intersect and here that the winners and losers in the game of life are recorded.

                                         N. Eldredge 

 

 Paleontological studies show that drastic changes in the environment have been associated with accelerated rates of evolution in metazoans. The empirically determined correlation between the rates of metazoan evolution and changes in environment continues to be at the center of a debate on the interactions organism-environment and the relative roles of the intrinsic and external factors in  evolution of metazoans. As open systems, metazoans, like all living beings, are in continuous interaction with their environment. Far from passive objects of environmental actions, metazoans have evolved mechanisms of adaptive responses to the adverse environmental influences. A principal adaptive response to such environmental influences in vertebrates is the stress response, which comprises adaptive changes in behavior, physiology, morphology and life histories under changed conditions of living. The stress response in vertebrates is determined by neural mechanisms and the main mediator of the response is the neuroendocrine system related to the function of a “physiological” classical stress circuit, the limbic-hypothalamic-pituitary-adrenal (LHPA) axis and  the central or “cognitive” stress circuitry.

 

Evolution of Animal Kingdom is Related to Changes in Environment

Paleontological evidence shows that all the major diversifications in metazoans, during last ~ 600 million years, including the Cambrian explosion, coincide with major shifts in the climatic and geological conditions that significantly affected their conditions of living. This correlation suggests that a causal relationship between the changes in the environment and the evolution of metazoans might exist.

The Cambrian explosion, as estimated by fossil record, began some 544 million years ago with the sudden appearance of almost 100 phyla, including all the 37 extant phyla (Erwin et al., 1997). Many paleontologists believe that eumetazoans evolved even earlier but, being soft-bodied, those animals left no fossils.

A number of studies on evolution of protein-coding loci suggest that the divergence between protostomes (arthropods, annelids, and molluscs) and deuterostomes (echinoderms and chordates) took place about 670 million years ago (Ayala et al., 1998) and the Cambrian explosion itself followed a mass extinction that occurred more than 540 million years ago (Kirschner and Gerhart, 1998). Cambrian explosion was characterized by rapid evolution of body plans, and the fact that the tempo of evolution at that time has been “unusually rapid” led to the suggestion that evolution of body plans at the time was related to the expansion of the range as a result of expansion to new empty niches and the end of body plan diversification by the mid-Cambrian is related to the saturation of new niches (Kirschner and Gerhart, 1998).

The Ordovician radiation, which took place by the end of the Cambrian period, about 500 million years ago, and by some estimates is considered to be larger than the Cambrian explosion, is characterized by a rapid appearance of numerous families (including crinoids, articulate brachiopods, cephalopods, and corals), genera, and species that dominated marine ecosystems for 250 million years (Droser et al., 1996). The extraordinary biological innovation of Ordovician is related to two drastic changes in the marine and terrestrial environments: a drop in the sea level and the intense orogenic activity of the earth that led to formation of many mountain ranges, which is suggested by the fact that the number of the marine taxa that diversified at the period was larger in the regions in the proximity of orogenic activity (Miller and Mao, 1995). The large scale climatic and ecological changes determined by those events might have led to the global diversification of Ordovician radiation (Droser et al., 1996).

Devonian was characterized by rapid diversification of fish and hence is also known as the Age of Fish. During this period, about 380-360 million years ago, began the colonization of land by plants, invertebrates, such as scorpions, and vertebrate tetrapods (archaic amphibians, such as Ichthyostega, and later reptiles). It is believed that during this period the biggest mass extinction of metazoans occurred. A paleontologically recorded retreat of the sea with its ecological and climatic consequences in the Ocean and in the land might have been the common cause for both the recorded mass extinction and the colonization of land during Devonian.

Next, Carboniferous period with its hyperoxic atmosphere is believed to have favored evolution of tetrapod locomotion and evolution of flight in both vertebrates and insects (Dudley, 1998). During the hypoxic Permian period, about 250 million years ago, the extinction of the last Cambrian fauna occurred and Paleozoic fauna rapidly declined. It is estimated that 96% of all species and 50% of families became extinct because of the formation of Pangea II (the bringing together of the continents as a result of plate tectonics). This marks the beginning of the Mesozoic Era, immediately followed by the modern fauna, whose origin is traced back to the Ordovician.

At the beginning of the Mesozoic, about 200 million years ago, marine life was dominated by molluscs. Reptiles, including dinosaurs, sustained by a thriving plant life, were the dominant terrestrial vertebrate class. Extinction of dinosaurs and the rise of mammals (which up to that point in time were represented by nocturnal insectivorous animals) by the end of Cretaceous, some 65 million years ago, has generally been related to various groups of geological factors such as intensification of volcanic activity, the fall of a huge meteor and a drop in the sea level, which have drastically changed the climate and conditions of living on earth (Ward, 1994a; Wilf et al., 2003).

No single cause was entirely responsible for the enormous species death. Volcanic paroxysms spewed huge quantities of gas into the atmosphere, raising the earth’s temperature through greenhouse heating and drastically altering atmospheric and oceanic circulation patterns in the process...a great drop in global sea level occurred, further perturbing the climate. And then, about a million years later, an enormous meteor struck the earth. (Ward, 1994b)

No convincing reason, however, is given as to why those factors that led to extinction of dinosaurs did favor the mammals at the same time.

The role of environmental changes in taxonomic diversification of metazoans may also be illustrated by the evolution of eutherian mammals, which have been documented for the Late Cretaceous, 85-90 million (Archibald et al., 2001) to Early Cretaceous, 125 million years ago (Ji et al., 2002). Global  warming during the Late Cretaceous is considered to have stimulated the rapid diversification and the dispersal of salamanders (Vieites, Min and Wake, 2007).

Earliest placentals is believed to have evolved ~86-90 million years ago (Archibald, 2003) and earliest placental mammals ~65 million years ago (Easteal, 1999). According to Meng and McKenna (1998), major evolutionary changes in placental mammals (eutherians) also took place during short periods of time coinciding with global climatic changes. First, during the warming (the mean annual temperature of 30⁰C) humid period of Palaeocene/Eocene, ~55 million years ago, which was characterized by dense forest areas. This period of taxonomic diversification was followed by a longer period of taxostasis. Then, during the Eocene/Oligocene boundary, 33.5 million years ago, a cooler and more arid period came that was characterized by disappearance of perissodactyl-dominant fauna, which was “replaced by rodent/lagomorph-dominant faunas of the Oligocene” (Meng and McKenna, 1998). A 4^o C drop of the winter temperature during that period is considered to be the cause of one of the largest extinctions of marine invertebrates during the whole Cenozoic (Ivany et al., 2000).

Radical climatic changes during the Miocene, ~20 million years ago, transformed Sahara region from a tropical to an arid environment. This transformation is believed, for example, to be the cause of the splitting of a single elephant species into two: the only elephant shrew species in the north of Sahara and a South of Sahara-residing species (Petrodromus tetradactylus), now belonging to a different genus (Douady et al., 2003).

As a result of the dry conditions during late Miocene Europe, hypsodont mammals, with high-crowned cheek teeth, succeeded in expanding their habitat (Jernvall and Fortelius, 2002).

Continued contraction of the wooded fruit-rich habitat to the low latitudes of Africa and Southeast Asia by late Miocene, about 10 million years ago, which coincided with a decrease in the diversity of great apes to these parts of the world and the dynamics of these habitats, are considered to be environmental factors to which these species responded by increasing their sociality and cognitive capabilities (Potts, 2004).

A study on the influence of ecological factors on evolution rates in 20 grouse taxa has  shown that habitat changes have induced higher rates of evolution of body proportions (Drovetsky et al., 2006). Repeated glaciation processes  also have had considerable influence in acceleration of evolutionary rates in metazoans:

 

Deep-sea organisms, such as benthic ostracods, exhibit fluctuations in diversity over time scales of 10,000 to 100,000 years that correlate with glaciation, diversity decreasing as glaciers advance and recovering during interglacial periods. (Cronin and Raymo, 1997)

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Neuroendocrine Mechanisms of Metazoan Homeostasis

 

In order to normally and undisturbedly perform their complex functions living systems have to create a stable internal environment. In unicellulars the genome functions as a regulatory device for maintaining their intracellular medium in a relatively steady state by interacting with the intracellular components, including both negative and positive feedback mechanisms responsible for the maintenance of most of the homeostatic parameters.

With multicellularity, an evolutionary pressure arose for a specialized system capable of  integrating and coordinating actions of all the cells the multicellular organisms consist of. This  requires maintenance of a stable “physiological” intercellular medium in which cells have to carry out their functions. In metazoans, this is function of the integrated control system (ICS), which is responsible for maintaining the homeostasis. 

The term homeostasis here will be used in a broader than the conventional meaning of the term, so as to include not only the maintenance of the physiological state of body fluids but the maintenance of the structural integrity of the organism as well.

As explained earlier in this work, the CNS represents the controller of the ICS. The function of the ICS requires continuous input of data in the CNS on the state of the system, whose structure is continually and unavoidably eroding. The input is compared with the normal state (neurally determined set points or thresholds) and on that basis decisions are made and instructions are sent for restoring the normal state. The nervous system uses specific signal cascades as communication channels for sending instructions to the target cells/organs. Thus, the homeostatic function implies the capability of the CNS for  “remembering” or having information on the normal state in the form of thresholds and set points.

Adversely and unpredictably changing environments challenge the homeostatic  capabilities of metazoans which have to adaptively respond to such environmental changes in order to survive.

Generally, the adaptation to drastic changes in environment begins with behavioral changes, which usually are accompanied by, or are related to, a state of environmental stress with all the characteristic neuroendocrine and behavioral correlates. This stress condition is an adaptive response of the organism to cope with adversely changing conditions of living and to reestablish the disturbed homeostasis.

The maintenance of homeostasis in metazoans is function of the neuroendocrine system which evolved at the dawn of the metazoan life as a result of the evolution of the nerve cell, neural net, the nervous system. Primitive metazoans had a nervous net but not a separate endocrine system, which evolved later as extension of the nervous system. Even the most primitive nervous net, as we know it in cnidarians, is capable of monitoring changes in the external and internal environments, processing the input, and communicating its output throughout the body in the form of chemical signals, neurosecretions, for inducing adaptive changes in behavior, physiology and morphology.

It is a widely held opinion that the first nerve cells to evolve might have been neurosecretory by function. The nerve cell, nerve net, and the central nervous systems evolved in response to the evolutionary pressures for maintaining homeostasis of evolving metazoan systems of ever-increasing structural and functional complexity, for dealing with impredictabilities of the changing environment and for appropriately reacting to avoid their harmful effects. It is believed that a first step in differentiation of the neuron has been differentiation of specialized receptor cells for monitoring changes in the external environment and communicating these changes to the rest of cells via chemical mediators they release (Gorbman and Davey, 1991f).

Most of hormonal systems in lower invertebrates are first-order systems, i.e. neurosecretory systems, with neurons being the only source of hormones for regulating the growth, metabolism, water balance, and reproduction.

In chordates and vertebrates, the hypothalamus took over most of the functions of communication with the rest of the body and regulation of homeostasis as well as adaptive responses to the changed environment. A process of centralization of the nervous system and formation of brain began very early in the evolution of metazoans. Parts of the brain would later specialize in performing adaptive-regulatory functions and an endocrine system would later evolve as an extension of the nervous system.

The neuroendocrine system in vertebrates regulates all the basic biological functions of growth, metabolism, and reproduction that were regulated by the neurosecretory system of the first order in lower invertebrates. Additionally, chiefly via the autonomous nervous system, it regulates the visceral activities (Strand, 1999h).

By mid-30es of the 20^th century, Ernst and Bertha Scharrer introduced the concept of an integrated neuroendocrine system in which neurons secreted their hormones into circulation (Strand, 1999a). The neural and non-neural tissues secrete a relatively a large number of neuropeptides necessary for integration of the functions of all the systems of organs in metazoans. These neuropeptides act as endocrine, paracrine, and autocrine hormones. Essential  in describing their function is the concept of the “window of opportunity”:

 

Depending on the tissue substrate, the stage of development, the metabolic state, the presence or absence of other hormones, growth factors, or even neurotransmitters, neuropeptide action may be highly specific, merely permissive, or perhaps even redundant. (Strand, 1999b)

 

Half a century ago, in 1949, it was demonstrated that a small neurosecretory part of brain (weighing only 4-5 grams in humans), the hypothalamus, was specialized for the communication between the CNS and the endocrine system. It is the most ancient part of the brain shared by an extremely wide range of metazoan taxa, from the lower vertebrates to mammals. In vertebrates the hypothalamus is highly conserved as to the cytoarchitecture, connectivity, neurochemistry (Greenspan, 1994).

The endocrine system consists of ductless glands that release their hormones into the bloodstream. The classic endocrine glands in higher vertebrates are the pituitary, thyroid, parathyroid, pancreas, thymus, and the gonads. Other organs in which clusters of secretory cells produce hormones are the liver (insulin-like growth factor 1), kidney (renin, erythropoietin, and vitamin D3), the pineal gland (melatonin) and the endocrine cells of the gut. The total number of hormones in humans exceeds 130 (Norman and Litwack, 1997g).

For a long time, the pituitary was considered to be the “master” gland, but now we know that this gland itself is subordinate to the hypothalamus, which controls the synthesis of pituitary hormones via specific -releasing and release-inhibiting hormones and neurotransmitters (the synthesis of some pituitary hormones is under the direct or indirect neuronal control) (Norman and Litwack, 1997b).

The hypothalamus itself secretes its “releasing” hormones from nerve endings of its peptidergic neurons in response to electrical/chemical signals it receives from aminergic or cholinergic neurons in various brain centers (Norman and Litwack, 1997a) often through the limbic system. These signals stimulate secretion of hypothalamic releasing hormones. These neurohormones enter the local blood circulation and are carried to the anterior pituitary via the hypothalamic-hypophyseal portal system where they bind specific receptors and via specific signal transduction pathways stimulate synthesis of specific pituitary hormones. Besides the releasing hormones, the hypothalamus also secretes a number of other hormonal polypeptides, which are also known to be secreted by secretory cells in various organs, including other regions of the CNS. Such neuropeptides are angiotensin II, gastrin, substance P, enkephalins, etc. The median eminence (ME) alone secretes more than 40 neuropeptides and other chemical messengers. Each of the hypothalamic releasing hormones controls the synthesis of a specific pituitary hormone, which, in turn, stimulates secretion of a specific hormone by the target endocrine glands.

Despite the involvement of other factors and its interaction with these factors, the neuroendocrine system functions as a hierarchical system  where the activation of an element induces activation of the downstream element in a chain of events that is conventionally described as signal cascade.

The hypothalamus monitors and regulates the body temperature, sodium chloride, glucose levels and the chemistry of body fluids in general. It controls most of the involuntary activities in the animal body, including innate behaviors. Through the pituitary gland, it determines the whole hormonal activity of the target endocrine glands, which is crucial for performing reproductive, developmental, behavioral, and other physiological functions.

As already mentioned, besides the hormonal control, the hypothalamus exerts a direct control on the pituitary, via a special anatomical structure enabling the close interaction between the nervous and endocrine systems, represented by nerve endings of hypothalamic neurosecretory neurons that project into pars nervosa of the pituitary. This enables the hypothalamus to discharge its releasing neurohormones directly into the portal vessels of the pituitary. The cascade action of hormones of the hypothalamus, the pituitary, and terminal endocrine glands made possible the emergence of what are known as  hypothalamic-pituitary-target endocrine glands axes and the neuroendocrine system, which play crucial role in maintaining metazoan homeostasis.

The close relationship between the nervous and endocrine systems makes possible the well-known influence of external and internal environments on the activity of the endocrine system. Studies by Walter R. Hess (1949) indicated that the hypothalamus is a coordinating center that integrates various inputs to ensure a well-organized, coherent, and appropriate set of autonomic (it is a motor nucleus for the autonomic nervous system) and endocrine responses.

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Stress and Stressors in Vertebrates

 

Sudden changes in environment often are so rapid that would not provide the time necessary for the gradual changes to accumulate, for the adaptation and survival of the animal in the new environment. Such environmental changes can invalidate various phenotypic adaptations species have evolved in the course of their phylogeny and individuals may suddenly find themselves in life-threatening situations. This is a time when the “struggle for life” may take its fiercest form. Each individual organism, population, and species, sometimes the whole ecotype, can face a survival crisis - often being doomed to extinction. At an organismic physiological level this situation is expressed with a general stress condition, and by effort, not always successful, for maintaining homeostasis.

Stress is defined as “a threat, real or implied, to the psychological or physiological integrity of an individual” (McEwen, 1999). According to D.S.Goldstein:

Stress is a condition where expectations—whether genetically programmed, established by prior learning, or deduced from circumstances—do not match the current or anticipated perceptions of the internal or external environment, and this discrepancy between what is observed or sensed and what is expected or programmed elicits patterned, compensatory responses. Distress is viewed here as a form of stress characterized by specific behavioral and autonomic communicated signs, pituitary-adrenocortical and sympatho-adrenomedullary activation, and a negative experience that motivates escape or avoidance. During stress, many body systems—including the sympathoadrenal, parasympathetic, and hormonal homeostatic systems—are activated or inhibited in primitively specific patterns regulated by physiological, biochemical, and psychological homeostats. (Goldstein, 1990)

From an evolutionary point of view, stress is a centrally determined adaptive response to the changed conditions in the environment that threaten species-specific homeostasis.

External factors leading to stress condition are known as stressors and their effect on the organism is known as stress condition. The concept of stress incorporates both an environmental agent (the stressor) adversely influencing the living system (stress condition) and a response of the affected animal for overcoming injurious effects of the stressor (stress response). The effects of the stressor depend not only on the nature of the stressor but also on the nature of the stressed animal in the meaning that what may be a stressor for one species may not be for another.

Two general types of stressors are distinguished, according to the duration of their action:

- long-term stressors, and

- short-term stressors.

Long-term stressors comprise drastic changes in the environment such as transformation of a terrestrial habitat into an aquatic one (or vice versa), the introduction of a specific predator into the habitat, severe changes in the climate and temperature, overcrowding and resulting food shortage, etc.

Short-term stressors, which by acting for short periods of time and stimulating fight-or-flight responses, are irrelevant from an evolutionary point of view.

Presently, many biologists consider stress to be a complex biological process, an organismic response fundamentally determined by neural (central and peripheral) mechanisms with the limbic-hypothalamus-pituitary-adrenal axis as the major player. Neuroendocrine implications of stress are complex and they depend on both the animal species and the nature of the stressor.

However different stressors might be, there is a common pattern of stress condition in higher vertebrate species characterized by a neuroendocrine response (activation of the hypothalamic-pituitary-adrenal axis) for restoring the disturbed homeostasis and by adaptation of the behavior to the changed environment.

Stressful situations activate two basic interacting and overlapping stress-response circuits: the central neural circuit and the neuroendocrine circuit. The first receives stress signals, which converge to the amygdala as the central stress processor. Activation of this circuit leads to the so-called “emotional” or “cognitive” stress. The neuroendocrine circuit consists of the limbic-hypothalamus-pituitary-adrenal axis and leads to the best known “physiological” stress (Avishai –Eliner et al., 2002; figure 8.1).

 

Neuroendocrine Response to Stress

 

Stress condition is a systemic condition arising when the intensity of the action of the stressor exceeds an intrinsically determined threshold. The threshold beyond which a noxious agent would act as a stressor varies not only between species but individuals of the same species may vary in their sensibility to stressors. Besides, different stressors may activate different neural pathways and elicit the release of ACTH (adrenocorticotropic hormone) and glucocorticoids through different neuroendocrine mechanisms and these specific neuroendocrine responses, in turn, may dramatically alter neuronal responses to corticosteroids. (Orchinik, 1998). There is adequate experimental evidence that those responses depend on the specific neuroendocrine context.

An adaptive response to the stress condition, i.e. to the adverse effects of environmental factors, implies before anything else an ability to perceive when that threshold is reached. The perception and evaluation of the stressor or its effects takes place in the nervous system.

Figure 8.1. Stress-activated pathways include the neuroendocrine hypothalamic–pituitary–adrenal axis (a) and the central, limbic stress-loop (b). (a) ‘Physiological’ stress signals reach the hypothalamus, causing secretion of corticotropin-releasing hormone (CRH) from neurons of the paraventricular nucleus (PVN). CRH induces release of adrenocorticotropic hormone (ACTH) from the pituitary, and ACTH elicits secretion of glucocorticoids (GCs) from the adrenal gland. GCs cross the blood–brain barrier and activate specific receptors in hippocampus (and other CNS regions) to ‘shut off’ the neuroendocrine stress response. By contrast, GCs increase CRH mRNA expression in the amygdala, facilitating stress-responses, whereas pituitary ACTH reduces CRH mRNA levels in the amygdala by direct activation of melanocortin receptors. (b) Stress involving higher-order sensory processing (i.e. with ‘cognitive’ and/or ‘emotional’ aspects) activates limbic pathways constituting the more recently elucidated ‘central’ stress circuit. Stressful stimuli reach the key processor, the central nucleus of the amygdala (ACe), activating the numerous CRH-producing neurons in this region. Locally released CRH acts on cognate receptors on projection neurons of the amygdala, which convey stress-related information (directly, or indirectly via the entorhinal cortex) to the hippocampal formation. Within the hippocampus, stress-induced release of CRH from interneurons in pyramidal-cell layers enhances synaptic efficacy and influences memory function. Arrows indicate facilitatory projections but do not imply monosynaptic connections. Blunt-ended lines denote inhibitory feedback loops.

Abbreviation: BST, bed nucleus of the stria terminalis (From Avishai-Eliner et al., 2002).

Both vertebrate and invertebrate organisms have evolved special systems for dealing with such adverse environmental influences, neuroendocrine stress-controlling mechanisms, representing essential part of the integrated control system (ICS), with the CNS as its controller.