152 research outputs found
Chronic psychosocial stressors in adulthood: Studies in mice, rats and tree shrews
No full textAbstractHuman psychological stress is the major environmental risk factor for major depression and certain of the anxiety disorders. Psychological stressors often occur in the context of the adult social environment, and they or the memory formed of them impact on the individual across an extended period, thereby constituting chronic psychosocial stress (CPS). Psychosocial stressors often involve loss to the individual, such as the ending of a social relationship or the onset of interpersonal conflict leading to loss of social control and predictability. Given the difficulty in studying the etio-pathophysiological processes mediating between CPS and brain and behavior pathologies in human, considerable effort has been undertaken to study manipulations of the social environment that constitute adulthood chronic psychosocial stressors in other mammals. The majority of such research has been conducted in rodents; the focus for a considerable time period was on rats and more recently both rats and mice have been investigated, the latter species in particular providing the opportunity for essential gene x chronic psychosocial stressor interaction studies. Key studies in the tree shrew demonstrate that this approach should not be limited to rodents, however. The animal adult CPS paradigms are based on resident-intruder confrontations. These are typified by the intruder-subject's brief proximate interactions with and attacks by, and otherwise continuous distal exposure to, the resident stressor. In contrast to humans where cognitive capacities are such that the stressor pertains in its physical absence, the periods of continuous distal exposure are apparently essential in these species. Whilst the focus of this review is on the stressor rather than the stress response, we also describe some of the depression- and anxiety disorder-relevant effects on behavior, physiology and brain structure-function of chronic psychosocial stressors, as well as evidence for the predictive validity of such models in terms of chronic antidepressant efficacy. Nonetheless, there are limitations in the methods used to date, most importantly the current emphasis on studying CPS in males, despite the much higher disorder prevalence in women compared to men. Future studies will need to address these limitations
Effects of antenatal dexamethasone treatment on glucocorticoid receptor and calcyon gene expression in the prefrontal cortex of neonatal and adult common marmoset monkeys
No full textBACKGROUND: Synthetic glucocorticoids such as dexamethasone (DEX) are commonly used to promote fetal lung maturation in at-risk preterm births, but there is emerging evidence of subsequent neurobehavioral abnormalities in these children e.g. problems with inattention/hyperactivity. However, molecular pathways mediating effects of glucocorticoid overexposure on motor and cognitive development are poorly understood. METHODS: In this study with common marmoset monkeys, we investigated for neonatal and adulthood effects of antenatal DEX treatment on the expression of the corticosteroid receptors and also calcyon, a risk gene for attention-deficit/hyperactivity disorder, in the prefrontal cortex (PFC). Pregnant marmosets were exposed to DEX (5 mg/kg body weight) or vehicle during early (days 42-48) or late (days 90-96) stages of the 144-day pregnancy. RESULTS: In neonates, relative to controls, glucocorticoid receptor (GR) mRNA levels were significantly reduced after the late DEX treatment in the medial, orbital and dorsal PFC and after the early DEX treatment in the dorsal PFC. The early DEX exposure, specifically, resulted in significant reduction in calcyon mRNA expression in the medial, orbital, dorsal and lateral PFC relative to controls. Mineralocorticoid receptor (MR) mRNA levels were not significantly affected by DEX treatment. In adults, PFC GR, calcyon, and MR mRNA levels were not significantly affected by early or late prenatal DEX treatment. CONCLUSION: These findings indicate that antenatal DEX treatment could lead to short-term alterations in PFC expression of the GR and calcyon genes, with possible neurodevelopmental functional consequences
The developmental impact of prenatal stress, prenatal dexamethasone and postnatal social stress on physiology, behaviour and neuroanatomy of primate offspring: studies in rhesus macaque and common marmoset
No full textRATIONALE: Exposure of the immature mammalian brain to stress factors, including stress levels of glucocorticoids, either prenatally or postnatally, is regarded as a major regulatory factor in short- and long-term brain function and, in human, as a major aetiological factor in neuropsychiatric disorders. Experimental human studies are not feasible and animal studies are required to demonstrate causality and elucidate mechanisms. A number of studies have been conducted and reviewed in rodents but there are relatively few studies in primates. OBJECTIVES: Here we present an overview of our published studies and some original data on the effects of: (1) prenatal stress on hypothalamic-pituitary-adrenal (HPA) re/activity and hippocampus neuroanatomy in juvenile-adolescent rhesus macaques; (2) prenatal dexamethasone (DEX) on HPA activity, behaviour and prefrontal cortex neuroanatomy in infant-adolescent common marmosets; (3) postnatal daily parental separation stress on HPA re/activity, behaviour, sleep and hippocampus and prefrontal cortex neuroanatomy in infant-adolescent common marmoset. RESULTS: Prenatal stress increased basal cortisol levels and reduced neurogenesis in macaque. Prenatal DEX was without effect on HPA activity and reduced social play and skilled motor behaviour in marmoset. Postnatal social stress increased basal cortisol levels, reduced social play, increased awakening and reduced hippocampal glucocorticoid and mineralocorticoid receptor expression in marmoset. CONCLUSIONS: Perinatal stress-related environmental events exert short- and long-term effects on HPA function, behaviour and brain status in rhesus macaque and common marmoset. The mechanisms mediating the enduring effects remain to be elucidated, with candidates including increased basal HPA function and epigenetic programming
Differential Excretion of Urinary Oestrogen by Breeding Females and Daughters in the Red-Bellied Tamarin (Saguinus labiatus)
No full textLlywelyn ab Iorwerth : the making of a Welsh prince
No full textLlywelyn ab Iorwerth (1173-1140) has long been considered one of the leading heroes of Wales. The life and rule of Llywelyn, known as Llywelyn the Great, is explored in detail in this thesis. The grandson of Owain Gwynedd, ruler of North Wales from 1137-1170, Llywelyn grew up during the period of turmoil following Owain’s death. After wresting control of Gwynedd from his rival family members in the latter decade of the 12th century, he proceeded to gain recognition as the foremost representative of Wales on the political stage.
Although viewed as a legendary hero in Welsh history, poetry and culture, Llywelyn's route to power is more complex than that. The thesis explores the development of the man from rebel and warlord, to leader and spokesman, to statesman, traces the expansion of his hegemony throughout Wales, and discusses the methods he used to gain and maintain power. Particular attention is paid to his use of family, marriage, allies, rivals and the church to achieve his goals. These insights can be derived from the surviving charters, letters, and other acta of Llywelyn and the Royal Chancery of England, the titles accorded therein, Welsh and English chronicles, as well as, occasionally, Venedotian Poetry. Finally, this thesis seeks to address the limitations on Llywelyn’s successes, in light of succeeding events and concludes with a discussion of Llywelyn’s legendary status in the modern world
Pathos and patter in real estate parlance
No full textThis paper presents the first systematic analysis of estate agent language and employs Aristotle’s ponderings on the art of persuasion as a means of classifying the peculiar parlance of property peddlers. “Des. Res.”, “rarely available”, “viewing essential” – these are all part of the peculiar parlance of housing advertisements. The question is whether the selling agent’s penchant for rhetoric is uniform across a single urban system or whether there are variations, even within a relatively limited geographical area. We are also interested in how the use of superlatives varies over the market cycle. For example, are estate agents more inclined to use hyperbole when the market is buoyant or when it is flat? This paper attempts to answer these questions by applying textual analysis to a unique dataset of 49,926 records of real estate transactions in the West of Scotland over the period 1999 to 2006. Our analysis has implications for our understanding of the agency behaviour of housing market professionals and endeavours to open up a new avenue of research into the market-impact of rhetoric in the language of selling
Postnatal ontogeny of hippocampal expression of the mineralocorticoid and glucocorticoid receptors in the common marmoset monkey
No full textThe mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) are nuclear transcription factors that mediate many of the basal and stress functions and effects of the corticosteroid hormones, including those related to brain development. Despite this, relatively little is known about the postnatal ontogeny of MR and GR gene and protein expression in the central nervous system, and this is particularly true of the primates, including humans. Here we describe the postnatal ontogeny of central MR and GR gene and protein expression in the common marmoset monkey. By developing marmoset-specific riboprobes and using in situ hybridization, it was demonstrated that MR mRNA expression in the dentate gyrus and Ammon's horn was significantly greater in marmoset infants (aged 4-6 weeks) than in neonates (1-2 days), juveniles (4-5 months) and adults (3-6 years), with expression in the latter three ontogenetic stages being broadly similar. In the same subjects and ontogenetic stages, GR mRNA expression was developmentally consistent in the marmoset dentate gyrus and Ammon's horn, as well as in the paraventricular nucleus of the hypothalamus. Qualitative immunohistochemical comparison of infants and adults demonstrated that MR protein expression in the hippocampus was, as for mRNA, also greater in infants than adults, and that hippocampal GR protein was, as for mRNA, also similar in infants and adults. The increase in MR mRNA expression between the stages of neonate and infant co-occurred with a reduction in basal plasma ACTH and cortisol titres. The ontogenetic profiles of MR and GR gene expression in the marmoset monkey are therefore fundamentally different from those described for the rat and the mouse. This evidence for the postnatal ontogeny of central corticosteroid nuclear receptor expression in a primate is important for understanding both the developmental stage-specific significance of stress exposure and its potential long-term effects on health and disease
Comparative evidence for the importance of the amygdala in regulating reward salience
No full textEnvironmental stimuli and life events are often of emotional relevance to the individual. This is due to their recognition and processing by the brain’s neural circuits for emotion. In terms of emotion valence, stimuli/events can be neutral (nonemotional), rewarding or aversive. In addition to its basic valence, the salience of an emotional stimulus, that is, how rewarding or how aversive it is, is also of critical importance. Quantitative changes in stimulus reward salience or aversion salience are likely to underlie some major symptoms in stressrelated mental disorders. This includes low reward salience as the basis for diminished interest or pleasure in major depressive disorder (MDD) and for apathy (negative symptoms) in schizophrenia, and high aversion salience as the basis for depressed mood in MDD. Insight into the brain region(s) and cellular microcircuits wherein the saliences of reward and aversion stimuli are set is essential for understanding the neurobiology of emotion in health and mental disorders. Here I review the current evidence for the role of the amygdala in processing reward valence and salience, based on studies conducted in human, monkey and, in particular, rat and mouse. Human BOLD-fMRI studies demonstrate amygdala reactivity to reward and its reduction in MDD and schizophrenia. In monkey, some neurons in the basolateral amygdala (BLA) are responsive to reward, aversion, or both. In rat, BLA reward neurons regulate excitation of nucleus accumbens (NAcc) neurons, whereas chronic stress increases intra-amygdala synaptic activity. In mouse, there are BLA glutamatergic principal reward neurons and aversion neurons. Based on this comparative evidence, this review concludes that the mammalian BLA reward neurons could constitute a major contributor to the neural circuitry of reward salience and a critical node in reward pathology
Cannabinoids for the control of experimental multiple sclerosis
No full textPhDThere have been numerous studies reporting that cannabinoids, both exogenous
and endogenous, have a potential beneficial function during incidences of
neurological damage. Using gene knockout mice and cannabinoid-selective agents,
this study demonstrates the diverse actions of cannabinoids with a particular focus
on experimental autoimmune encephalomyelitis, an animal model of multiple
sclerosis. The results presented here report on the action of stimulators of
cannabinoid receptors in the nervous system (CNS) on; immune function, as a
mechanism of suppressing autoimmune attack of the central nervous system, as
agents to suppress neurodegenerative events leading to disease progression and as
agents that can control signs of disease that occur as the consequences of
autoimmune neurodegeneration such as spasticity. Tetrahydrocannabinol the
psychoactive component in cannabis and the CB1 cannabinoid receptor appears to
be central to many of the therapeutic actions of cannabis but also to the side-effect
potential of cannabinoid drugs. This study reports on methods to avoid
psychoactive side-effects of conventional brain-penetrant CB1 receptor agonists
whilst exploiting the therapeutic potential of the cannabinoid system in order to
control spasticity. This was achieved by targeting mechanisms of endocannabinoid
degradation, particularly using fatty acid amide hydrolase inhibitors. Furthermore,
this study also reports the development of novel cannabinoid compounds that are
excluded from the brain and inhibit spasticity and also demonstrates the
mechanism of exclusion of CNS-excluded cannabinoid CB1 receptor agonists. This
study provides further evidence for the efficacy of cannabinoid compounds during
an ongoing CNS disease and also their efficacy for treating the consequences of
CNS autoimmune disease, which hopefully, will give additional impetus for further
clinical investigations of cannabinoid agents in not only multiple sclerosis but also
other neurodegenerative diseases of the CNS
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