Mental processes and disorders: A neurobehavioral perspective in human biometeorology

Summary Research concerning the complex relation between weather and psychological processes has emphasized three important issues: methodological problems, the determination of the major behavioral factors, and the isolation of neurobiological mechanisms. This paper reviews the current status of each issue. Weather changes are most frequently associated with behaviors that are the endpoints of inferred psychological processes that include mood, subclinical pain, anxiety, and the correlates of schedule shifts. Learning and conditioning appear to mediate a powerful influence over weather-related responses. This may explain the large individual variability in these behaviors. The most well-known group effects associated with weather changes involve psychiatric populations. Clinical subpopulations may respond in different ways to different aspects of the same weather system as well as to different types of air masses. Likely neurobiological mechanisms through which meteorogenic stimuli may mediate whole organismic effects include the locus coeruleal and limbic systems. Expected psychobiological consequences are examined in detail. The magnitude and temporal-spatial characteristics of weather effects indicate they are the subject matter of behavioral epidemiology.     

Neural mechanisms of operant conditioning and learning-induced behavioral plasticity in <Emphasis Type="Italic">Aplysia</Emphasis>

Associative learning in goal-directed behaviors, in contrast to reflexive behaviors, can alter processes of decision-making in the selection of appropriate action and its initiation, thereby enabling animals, including humans, to gain a predictive understanding of their external environment. In the mollusc Aplysia, recent studies on appetitive operant conditioning in which the animal learns about the positive consequences of its behavior have provided insights into this form of associative learning which, although ubiquitous, remains mechanistically poorly understood. The findings support increasing evidence that central circuit- and cell-wide sites other than chemical synaptic connections, including electrical coupling and membrane conductances controlling intrinsic neuronal excitability and underlying voltage-dependent plateauing or oscillatory mechanisms, may serve as the neural substrates for behavioral plasticity resulting from operant conditioning. Aplysia therefore continues to provide a model system for understanding learning and memory formation that enables establishing the neurobiological links between behavioral, network, and cellular levels of analysis.     

Geopsychology and geopsychopathology: Mental processes and disorders associated with geochemical and geophysical factors

Summary Temporal and regional variations in psychological processes have been associated with three geological factors. They are geochemical profiles, geomagnetic variations, and tectonic stresses. In the geochemical domain, copper, aluminum, zinc, and lithium may influence the incidence of thought disorders such as schizophrenia and senile dementia. These common elements are found in many soils and ground water. Geomagnetic variations have been correlated with enhanced anxiety, sleep disturbances, altered moods, and greater incidences of psychiatric admissions. The effects are usually brief but pervasive. Transient and very local epidemics of bizarre and unusual behaviors are sociological phenomena that sometimes precede increases in earthquake activity within a region; they have been hypothesized to be associated with tectonic strain. Many of the contemporary correlations between geological factors and human behavior are also apparent within historical data. The effects of geophysical and geochemical factors upon human behavior are not artifactual, but they are complex and often not detected by the limited scope of most studies.     

Geopsychology and geopsychopathology: mental processes and disorders associated with geochemical and geophysical factors

Temporal and regional variations in psychological processes have been associated with three geological factors. They are geochemical profiles, geomagnetic variations, and tectonic stresses. In the geochemical domain, copper, aluminum, zinc, and lithium may influence the incidence of thought disorders such as schizophrenia and senile dementia. These common elements are found in many soils and ground water. Geomagnetic variations have been correlated with enhanced anxiety, sleep disturbances, altered moods, and greater incidences of psychiatric admissions. The effects are usually brief but pervasive. Transient and very local epidemics of bizarre and unusual behaviors are sociological phenomena that sometimes precede increases in earthquake activity within a region; they have been hypothesized to be associated with tectonic strain. Many of the contemporary correlations between geological factors and human behavior are also apparent within historical data. The effects of geophysical and geochemical factors upon human behavior are not artifactual, but they are complex and often not detected by the limited scope of most studies.     

Development of behavior and learning in Aplysia

A set of fundamental issues in neuroethology concerns the neural mechanisms underlying behavior and behavioral plasticity. We have recently analyzed these issues by combining a simple systems approach in the marine mollusc Aplysia with a developmental analysis aimed at examining the emergence and maturation of different forms of behavior and learning. We have focussed on two kinds of questions: 1) How are specific neural circuits developmentally assembled to mediate different types of behaviors? and 2) how is plasticity integrated with these circuits to give rise to different forms of learning? From our analysis of the development of learning and memory in Aplysia, several themes have emerged: 1) Different forms of learning emerge according to different developmental timetables. 2) Cellular analogs of learning have the same developmental timetables as their respective forms of behavioral learning. 3) An analysis of non-decremented responses prior to the emergence of sensitization reveals a novel inhibitory process on both behavioral and cellular levels. 4) Sensitization emerges simultaneously in diverse response systems, suggesting an underlying general process. 5) A widespread proliferation of central neurons occurs in the same developmental stage as the emergence of sensitization, raising the possibility that some aspect of the trigger for neuronal proliferation may also contribute to the expression of sensitization.     

Memory

In this review we address the idea that conservation of epigenetic mechanisms for information storage represents a unifying model in biology, with epigenetic mechanisms being utilized for cellular memory at levels from behavioral memory to development to cellular differentiation. Epigenetic mechanisms typically involve alterations in chromatin structure, which in turn regulate gene expression. An emerging idea is that the regulation of chromatin structure through histone acetylation and DNA methylation may mediate long-lasting behavioral change in the context of learning and memory. We find this idea fascinating because similar mechanisms are used for triggering and storing long-term 'memory' at the cellular level, for example when cells differentiate. An additional intriguing aspect of the hypothesis of a role for epigenetic mechanisms in information storage is that lifelong behavioral memory storage may involve lasting changes in the physical, three-dimensional structure of DNA itself.     

Mechanisms of circulatory homeostasis and response in Aplysia.

This review concerns the organization and function of arterial vasculature in Aplysia californica, especially the vasomotor reflexes that support circulatory homeostasis, and fixed patterns of response that may reroute blood flow during changes in behavioral state. The observations presented here raise three hypotheses for further study: 1) Arterial vasculature is functionally organized with precisely structured, independently regulated subdivisions; these are most evident for arterial systems serving digestive and reproductive processes; 2) arterial musculature is inherently responsive to local pressure changes, having both static and dynamic reflexes that promote efficient, evenly-distributed flow of blood; and 3) complex, long-lasting behaviors like egg laying have, as part of their makeup, equally prolonged and stereotypical changes in the pattern of circulation. Taken together, these observations support the view that maintenance and adjustment of blood flow in gastropod molluscs is an unexpectedly complex and highly integrated component of behavior.     

Development of behavior and learning inAplysia

Summary A set of fundamental issues in neuroethology concerns the neural mechanisms underlying behavior and behavioral plasticity. We have recently analyzed these issues by combining a simple systems approach in the marine molluscAplysia with a developmental analysis aimed at examining the emergence and maturation of different forms of behavior and learning. We have focussed on two kinds of questions: 1) How are specific neural circuits developmentally assembled to mediate different types of behaviors? and 2) how is plasticity integrated with these circuits to give rise to different forms of learning? From our analysis of the development of learning and memory inAplysia, several themes have emerged: 1) Different forms of learning emerge according to different developmental timetables. 2) Cellular analogs of learning have the same developmental timetables as their respective forms of behavioral learing. 3) An analysis of non-decremented responses prior to the emergence of sensitization reveals a novel inhibitory process on both behavioral and cellular levels. 4) Sensitization emerges simultaneously in diverse response systems, suggesting an underlying general process. 5) A widespread proliferation of central neurons occurs in the same developmental stage as the emergence of sensitization, raising the possibility that some aspect of the trigger for neuronal proliferation may also contribute to the expression of sensitization.     

Mechanisms of circulatory homeostasis and response inAplysia

This review concerns the organization and function of arterial vasculature inAplysia californica, especially the vasomotor reflexes that support circulatory homeostasis, and fixed patterns of response that may reroute blood flow during changes in behavioral state. The observations presented here raise three hypotheses for further study: 1)Arterial vasculature is functionally organized with precisely structured, independently regulated subdivisions; these are most evident for arterial systems serving digestive and reproductive processes; 2) arterial musculature is inherently responsive to local pressure changes, having both static and dynamic reflexes that promote efficient, evenly-distributed flow of blood; and 3) complex, long-lasting behaviors like egg laying have, as part of their makeup, equally prolonged and stereotypical changes in the pattern of circulation. Taken together, these observations support the view that maintenance and adjustment of blood flow in gastropod molluscs is an unexpectedly complex and highly integrated component of behavior.     

Role of bombesin-related peptides in the mediation or integration of the stress response

In addition to the relatively well established role of corticotropin-releasing hormone (CRH) and arginine-vasopressin (AVP) in the mediation of the stress response, there is reason to believe that bombesin-like peptides (BN-LPs) may also contribute to the mediation or integration of these responses and thus might be considered as putative 'stress peptides'. This review provides evidence supporting this contention by showing that (i) BN-LPs are present at brain sites known to be activated by stressors, (ii) stressor exposure alters utilization of BN-related peptides, (iii) exogenous BN administration mimics the endocrine, autonomic and/or behavioral effects elicited by stressors, and (iv) antagonism of BN action attenuates the behavioral and/or neurochemical effects of stressors or of exogenously administered peptide. The evidence presented also suggests that BN-LPs mediate their stress-relevant effects through activation of CRH and/or AVP neurons. Several hypothetical mechanisms for such peptidergic interactions are discussed as to the implications of considering BN-LPs as 'stress peptides'. Received 16 July 2001; received after revision 27 August 2001; accepted 28 August 2001     

Memory

Our understanding of the cellular and molecular mechanisms underlying learning and memory formation derives from studies of species as diverse as worms, mollusks, insects, birds and mammals. Despite the quite different brain structures and neuronal networks, the studies support the current notion that neuronal activity leads to changes in synaptic connections as the neural substrate of behavioral plasticity. The analysis of the mechanisms underlying learning and memory formation reveals a surprisingly high conservation between invertebrates and mammals, both at the behavioral as well as the molecular level. This special issue provides an overview of the current knowledge on cellular and molecular processes underlying memory formation. The contributing reviews summarize the findings in different organisms, such as Aplysia, Drosophila, honeybees and mammals, and discuss new approaches, developments and hypotheses all aimed at understanding how the nervous system acquires, stores and retrieves information.     

Recognition of apoptotic cells by phagocytes

Effective removal of dying cells is crucial to a variety of processes in health and disease. Cells undergoing apoptosis are recognized and ingested intact by phagocytes, which are not stimulated to release inflammatory mediators. The alternative uncontrolled form of cell death, necrosis, is associated with release of cell contents with the potential to cause tissue damage and inflammation. Four distinct molecular mechanisms have been identified to date which mediate recognition by phagocytes of mammalian cells undergoing apoptosis, but further mechanisms remain to be discovered. The capacity for phagocyte removal of cells undergoing apoptosis may be closely regulated, for example by local cytokines.     

Adult neurogenesis in Parkinson’s disease

Parkinson’s disease (PD), the second most common neurodegenerative disorder, affects 1–2 % of humans aged 60 years and older. The diagnosis of PD is based on motor symptoms such as bradykinesia, rigidity, tremor, and postural instability associated with the striatal dopaminergic deficit that is linked to neurodegenerative processes in the substantia nigra (SN). In the past, cellular replacement strategies have been evaluated for their potential to alleviate these symptoms. Adult neurogenesis, the generation of new neurons within two proliferative niches in the adult brain, is being intensively studied as one potential mode for cell-based therapies. The subventricular zone provides new neurons for the olfactory bulb functionally contributing to olfaction. The subgranular zone of the hippocampus produces new granule neurons for the dentate gyrus, required for memory formation and proper processing of anxiety provoking stimuli. Recent years have revealed that PD is associated with non-motor symptoms such as hyposmia, anhedonia, lack of novelty seeking behavior, depression, and anxiety that are not directly associated with neurodegenerative processes in the SN. This broad spectrum of non-motor symptoms may partly rely on proper olfactorial processing and hippocampal function. Therefore, it is conceivable that some non-motor deficits in PD are related to defective adult neurogenesis. Accordingly, in animal models and postmortem studies of PD, adult neurogenesis is severely affected, although the exact mechanisms and effects of these changes are not yet fully understood or are under debate due to conflicting results. Here, we review the current concepts related to the dynamic interplay between endogenous cellular plasticity and PD-associated pathology.     

Nature/nurture and the nature of nurture in the etiology of hypertension.

Four reviews on the the role of developmental factors in hypertension are introduced and set in historical context. Recent research in the laboratory rat has shown that the preweaning environment makes an important contribution to the level of blood-pressure reached in adult life in genetic models of hypertension. Both of the most commonly used models of hypertension, the SHR and SS/Jr rat strains, exhibit lower BP in adult life, if they are fostered shortly after birth to mothers from their normotensive control strains. It has been suggested that it is the idiosyncratic maternal behavior of the hypertensive mothers which contributes to the elevated BP of their offspring, and it has been amply demonstrated that there is an association between a constellation of behaviors emitted by rat mothers and the adult BP of their offspring in a wide variety of genetic groups (inbred hypertensive animals, F1's and F2's). In addition to the above, maternal environment has been demonstrated to have a significant impact on the pathophysiological response of hypertensive animals to a high salt diet. Being raised by an SHR mother, versus an SS/Jr mother, increases the magnitude of BP increases to a high salt diet, susceptibility to hemorrhagic stroke, body weight loss and the risk of mortality. A variety of physiological systems are undergoing rapid change during the preweaning period and may mediate the effects of differences in the maternal environment. These include the renin-angiotensin system and the peripheral sympathetic nervous system. Nutritional factors may be involved in all of the phenomena referred to above. Thus, any physiological mechanisms that are proposed to link maternal behavior to its effects on the physiology of adult animals should recognize the involvement of nutritional factors. Research on the role of developmental factors such as maternal behavior in genetic models of hypertension is at the interface of two growing disciplines: behavior genetics and developmental psychobiology. The methodological and conceptual contributions of these fields to advancing our understanding of these phenomena is emphasized.     

Advances in tenascin-C biology

Tenascin-C is an extracellular matrix glycoprotein that is specifically and transiently expressed upon tissue injury. Upon tissue damage, tenascin-C plays a multitude of different roles that mediate both inflammatory and fibrotic processes to enable effective tissue repair. In the last decade, emerging evidence has demonstrated a vital role for tenascin-C in cardiac and arterial injury, tumor angiogenesis and metastasis, as well as in modulating stem cell behavior. Here we highlight the molecular mechanisms by which tenascin-C mediates these effects and discuss the implications of mis-regulated tenascin-C expression in driving disease pathology.     

Genetic models in brain and behavior research,part IV

Four reviews on the the role of developmental factors in hypertension are introduced and set in historical context. Recent research in the laboratory rat has shown that the preweaning environment makes an important contribution to the level of blod-pressure reached in adult life in genetic models of hypertension. Both of the most commonly used models of hypertension, the SHR and SS/Jr rat strains, exhibit lower BP in adult life, if they are fostered shortly after birth to mothers from their normotensive control strains. It has been suggested that it is the idiosyncratic maternal behavior of the hypertensive mothers which contributes to the elevated BP of their offspring, and it has been amply demonstrated that there is an association between a constellation of behaviors emitted by rat mothers and the adult BP of their offspring in a wide variety of genetic groups (inbred hypertensive animals, F1's and F2's). In addition to the above, maternal environment has been demonstrated to have a significant impact on the pathophysiological response of hypertensive animals to a high salt diet. Being raised by an SHR mother, versus an SS/Jr mother, increases the magnitude of BP increases to a high salt diet, susceptibility to hemorrhagic stroke, body weight loss and the risk of mortality. A variety of physiological systems are undergoing rapid change during the preweaning period and may mediate the effects of differences in the maternal environment. These include the renin-angiotensin system and the peripheral sympathetic nervous system. Nutritional factors may be involved in all of the phenomena referred to above. Thus, any physiological mechanisms that are proposed to link maternal behavior to its effects on the physiology of adult animals should recognize the involvement of nutritional factors. Research on the role of developmental factors such as maternal behavior in genetic models of hypertension is at the interface of two growing disciplines: behavior genetics and developmental psychobiology. The methodological and conceptual contributions of these fields to advancing our understanding of these phenomena is emphasized.     

Genetic studies of diseases

Functional imaging techniques such as positron and single-photon emission tomography exploit the relationship between neural activity, energy demand and cerebral blood flow to functionally map the brain. Despite the fact that neurobiological processes are not completely understood, several results have revealed the signals that trigger the metabolic and vascular changes accompanying variations in neural activity. Advances in this field have demonstrated that release of the major excitatory neurotransmitter glutamate initiates diverse signaling processes between neurons, astrocytes and blood perfusion, and that this signaling is crucial for the occurrence of brain imaging signals. Better understanding of the neural sites of energy consumption and the temporal correlation between energy demand, energy consumption and associated cerebrovascular hemodynamics gives novel insight into the potential of these imaging tools in the study of metabolic neurodegenerative disorders.     

The role of dietary carbohydrates in organismal aging

Carbohydrates are essential nutrients that are used as a primary source of energy. Carbohydrate utilization should be properly controlled, as abnormal regulation of carbohydrate metabolism is associated with diseases, such as diabetes, cardiovascular diseases, and stroke. These metabolic syndromes have become a serious problem in developed countries, and there is an increased need for research examining the influence of carbohydrates on animal physiology. Diets enriched in glucose, a major carbohydrate, are also associated with accelerated aging in several model organisms, including yeast and Caenorhabditis elegans (C. elegans). Genetic factors that mediate the effects of high glucose diets on aging have been identified during the last decade, mostly through the use of C. elegans. In this review, we describe studies that determine the effects of carbohydrate-enriched diets on aging by focusing on the mechanisms through which evolutionarily conserved pathways mediate the lifespan-altering effects of glucose in C. elegans. These include the insulin/insulin-like growth factor-1, sterol-regulatory element-binding protein, and AMP-activated protein kinase signaling pathways. We also discuss the effects of various carbohydrates and carbohydrate-derived metabolites on aging in model organisms and cultured mammalian cells. Finally, we discuss how dietary carbohydrates influence health and aging in humans.     

The cytotoxicity of eosinophil cationic protein/ribonuclease 3 on eukaryotic cell lines takes place through its aggregation on the cell membrane

Human eosinophil cationic protein (ECP)/ ribonuclease 3 (RNase 3) is a protein secreted from the secondary granules of activated eosinophils. Specific properties of ECP contribute to its cytotoxic activities associated with defense mechanisms. In this work the ECP cytotoxic activity on eukaryotic cell lines is analyzed. The ECP effects begin with its binding and aggregation to the cell surface, altering the cell membrane permeability and modifying the cell ionic equilibrium. No internalization of the protein is observed. These signals induce cell-specific morphological and biochemical changes such as chromatin condensation, reversion of membrane asymmetry, reactive oxygen species production and activation of caspase-3-like activity and, eventually, cell death. However, the ribonuclease activity component of ECP is not involved in this process as no RNA degradation is observed. In summary, the cytotoxic effect of ECP is attained through a mechanism different from that of other cytotoxic RNases and may be related with the ECP accumulation associated with the inflammatory processes, in which eosinophils are present. Received 26 October 2007; accepted 23 November 2007