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Biomedical subjects

Stefano Parmigiani

Publications and source records attributed to Stefano Parmigiani.

11 recordsLinked to original sources
PubMed2005

Escalated aggressive behavior: dopamine, serotonin and GABA.

The ethical dilemma in aggression research is how to reconcile two divergent objectives, namely to avoid harm and injury as much as possible and, at the same time, how to study behavioral phenomena that validly represent the essence of the neurobiology of aggression. Clinical and preclinical aggression research focuses on different types of aggression. Preclinical studies are usually stimulated by an ethological approach and focus on the phylogeny, ontogeny, survival value and neural mechanisms of ritualized displays and signals. On the other hand, clinical studies focus on violent individuals and pathologically excessive forms of aggressive behavior. This review emphasizes research on escalated forms of aggression in animals and humans and their pharmacotherapy. The current experimental models to generate escalated levels of aggressive behavior in laboratory rely on social instigation, frustrative non-reward and alcohol drinking. These types of aggression are modulated by canonical neurotransmitters like dopamine, serotonin (5-HT) and GABA. It continues to be a main goal of much neurobiological research to find potential targets of pharmacological agents that interact with dopaminergic, GABAergic and serotonergic systems and have high efficacy and selectivity to reduce excessive levels of aggressive and violent behaviors without side-effects. While the mesocorticolimbic dopamine system is implicated in the initiation, execution, termination and consequences of aggressive behavior, drugs with a high affinity for dopamine D2 receptors lack specificity for reducing aggressive behavior. Current investigations point to 5-HT(1B) receptor subtypes as particularly relevant. First, they are differentially expressed in aggression-prone individuals relative to those who are not excessively aggressive. Second, these and also other 5-HT receptor subtypes emerge to be significant targets for anti-aggressive interventions. Positive modulators of GABA(A) receptors with specific subunit configuration may be relevant for heightening aggression, and these sites may be targets for intervention. A prerequisite for rational pharmacotherapies will be adequate characterization of serotonergic and GABAergic receptor regulation in individuals exhibiting escalated aggression.

Aggression↗
PubMed2005

Serotonin and aggressive behavior in rodents and nonhuman primates: predispositions and plasticity.

This review analyzes psychosocial and genetic determinants of aggressive behavior in rodents and nonhuman primates and the role of the serotonin (5-HT) system on aggressive behaviors in order to trace possible evolutionary common origins between psychopathological and adaptive forms of aggression. Studies in primates suggest that deficit in serotonin activity, as indicated by the levels of the cerebrospinal fluid (CSF) serotonin major metabolite 5-hydroxyindoleacetic acid (5-HIAA) correlates with impulsive and aggressive behavior. It is possible that CSF 5-HIAA reflects the prevailing serotonergic tone and may be related to an aggressive trait. Superimposed on this tone are phasic serotonin changes that may be related to the inhibition of aggressive acts. Genetic factors determine aggressive behaviors as demonstrated by classic selection and strain comparison studies. Manipulations of genes targeting 5-HT receptors, transporters and enzymes can influence aggression. Some of these genes related to the serotonin transporter (5-HTT) and the monoamine oxidase A (MAO-A) show a polymorphism that may predispose, under specific environmental conditions, certain individuals to display pathological forms of aggression.

Aggression↗
PubMed2004

Social factors and individual vulnerability to chronic stress exposure.

The stress-response is adaptive in the short-term, but it can be maladaptive if sustained levels of its mediators are chronically maintained. Furthermore, not all individuals exposed to chronic stress will progress to disease. Thus, understanding the causes of individual differences and the consequences of variation in vulnerability is of major importance. The aim of this review is to shed light on this issue by presenting a new naturalistic model of chronic psychosocial stress in male mice. Resident/intruder pairs of mice lived in continuous sensory contact and physically interacted daily. Four categories were identified: Resident Dominant, Resident Subordinate (RS), Intruder Dominant, and Intruder Subordinate. Behavior, autonomic and immune functions, hypothalamic-pituitary-adrenocortical responses, brain cytokine expression and cardiac histology were investigated in stress-exposed mice. Certain stress-induced alterations were present in all mice independent of their social status, while others clearly differentiated dominants from subordinates. RS mice showed a unique profile of alterations suggesting that the loss of relevant resources, such as the territory, is the key factor determining why only certain stress-exposed individuals ultimately show malignancy and psychopathologies.

Aggression↗
PubMed2004

Age at group formation alters behavior and physiology in male but not female CD-1 mice.

In the laboratory environment, rodents are usually housed in unisexual groups, which are assembled after weaning. Housing of unfamiliar subjects has been described, however, as a stressful social setting for rodents and other mammals. Aim of the present study was to evaluate whether the age at which house mice are grouped might affect their behavior and physiology. Male or female unisexual groups were formed at different ages: at weaning, i.e., before puberty (JUV); at adolescence, i.e., after puberty (AD); and controls were raised with siblings since birth (CON). Results show that age at group formation induced several behavioral and physiological alterations in males but not in females. Specifically, when compared to controls, JUV males showed higher aggression, smaller preputial gland, and a marked reduction of neophobia in the free exploratory paradigm. Fewer changes occurred in the AD males, which showed reduced neophobia in the free exploratory paradigm and, when adults, a reduction in body weight. Females were not affected by the experimental treatment. Surprisingly, the basal corticosterone assessed at the nadir was lower for both males and females JUV and AD respect to CON. In conclusion, it is clear that mixing groups at different ages has profound effects on mouse behavior and physiology.

Aggression↗
PubMed2004

Behavioral and physiological characterization of male mice under chronic psychosocial stress.

Social stress is a major factor in the etiology of several psychopathologies, with individuals greatly differing in vulnerability. The development of appropriate animal models of social stress is, thus, a major challenge of modern bio-medical research. Adult male mice were subjected to a new model of chronic psychosocial stress in which resident/intruder dyads live chronically in sensory contact and physically interact on a daily basis. Four behavioral categories were identified: Resident Dominants (RD), Resident Subordinates (RS), Intruder Dominants (InD), Intruder Subordinates (InS). Here we investigated: behavior during aggressive interactions; gross physiological components of mice metabolism; organ physiology; response to dexamethasone suppression test (DST). RD and InD mice showed persistently high levels of aggression. All four categories of mice showed robust lack of suppression of corticosterone level when challenged with the DST. Although food intake was not altered under chronic stress, body weight decreased in RD and InD mice while increased in InS and, even more so, in RS mice, suggesting an alteration of their metabolic functions. In conclusion, social status and territory ownership were factors determining individual vulnerability to stress exposure. Our model could, thus, be regarded as a valid model to investigate the biological basis of the individual differences in the response to stressful events.

Aggression↗
PubMed2003

Chronic psychosocial stress down-regulates central cytokines mRNA.

Brain cytokines have been implicated in brain plasticity and mood alterations. We present here the first evidence of a chronic stress-induced modulation of central cytokines, in absence of experimentally induced inflammatory processes. Several brain areas were extracted from stressed and control mice and cytokines mRNA analyzed with semi-quantitative RT-PCR. Mice subjected to chronic psychosocial stress showed decreased interleukin (IL)-1beta mRNA levels in the hippocampus, decreased IL-1Receptor antagonist in the striatum and pituitary, decreased tumor necrosis factor (TNF)-alpha in the striatum and hippocampus, and decreased glucocorticoid receptor (GR) in the striatum and hippocampus compared to group housed sibling mice. An independent group of mice subjected to chronic psychosocial stress also showed increased plasma corticosterone. These findings may open new perspectives for understanding the pathophysiological basis of chronic stress-induced disorders.

Animals↗
PubMed2003

Chronic psychosocial stress persistently alters autonomic function and physical activity in mice.

We investigated heart rate (HR), temperature (T), and physical activity (Act) (by means of radiotelemetry) in male mice subjected to chronic psychosocial stress. Resident/intruder dyads lived in sensory contact for 15 days with the possibility to physically interact daily during the light phase for a maximum of 15 min. Intruders becoming dominants (InD) or subordinates (InS) were investigated here. The aims were to investigate; if a daily aggressive interaction would result in adaptation of autonomic responses; the effects of the social stress on daily rhythmicity and the way these effects change over time; whether acute and long-term autonomic changes do correlate; to compare dominants and subordinates. InD and InS showed a strong autonomic activation during the interactions, with moderate (InS) or no (InD) habituation over time. On the long term, InD showed tachycardia and marked hyperthermia but normal physical activity, while InS showed tachycardia, slight hyperthermia, and depressed physical activity. No correlation emerged between the acute and the long-term autonomic responses. These results highlight the existence of a sustained autonomic activation under chronic stress, which was also affected by mice social status.

Adaptation, Physiological↗
PubMed2003

Chronic psychosocial stress-induced down-regulation of immunity depends upon individual factors.

The effect of chronic stress on immune functions is strongly biased by individual factors. Mice were subjected to a new model of chronic psychosocial stress in which four different subcategories of stressed animals may be identified: Resident Dominants (RD), Resident Subordinates (RS), Intruder Dominants (InD), and Intruder Subordinates (InS). After 7 days of stress, mice were immunized with keyhole limpet hemocyanine (KLH). Their immune functions were investigated 14 days later with stress continuing trough. Importantly, RS mice, which are mice losing territory ownership, were the more affected, having lower IgG, proliferation, and IL-2. RD and InD showed lower IgG while InS showed no immune alteration. In conclusion, loss of resources could be a key factor in determining individual vulnerability to stressful events.

Agonistic Behavior↗
PubMed2003

The era of pulmonary surfactant from Laplace to nowadays.

The first observations on neonatal respiratory distress syndrome (RDS) were published by some obstetricians in England, France and Germany in the second half of the 18th century. The concept that RDS might involve the absence of something stems from the observations of a Swiss physiologist, Kurt von Neergaard, who published an article in 1929 about a fundamental principle of respiratory mechanics: the surface tension in the alveoli. Further early descriptions of the existence, composition, and synthesis of the surfactant complex and its physiologic role in maintaining alveolar stability were dependent on the pioneering contributions of Radford, Macklin, Pattle, and Clements (among others). But the final link, describing surfactant deficiency as a cause of RDS, came from Avery and Mead in 1959, when they showed lung extracts from babies with hyaline membrane disease deficient in surfactant. Understanding surfactant composition, function and therapeutic usefulness has increased exponentially over the last 50 years and this paper reorganizes the steps of the research in this field until nowadays. Most of the discussion concerns the fundamental role of lung surfactant in RDS of premature infants, and the success of exogenous surfactant replacement in the clinical therapy of this disease.

Animals↗
PubMed2002

Exposure to a low dose of bisphenol A during fetal life or in adulthood alters maternal behavior in mice.

Maternal behavior in mammals is the result of a complex interaction between the lactating dam and her developing offspring. Slight perturbations of any of the components of the mother-infant interaction may result in alterations of the behavior of the mother and/or of the offspring. We studied the effects of exposure of female CD-1 mice to the estrogenic chemical bisphenol A (BPA) during fetal life and/or in adulthood during the last part of pregnancy on subsequent maternal behavior. Pregnant females were fed daily doses of corn oil (controls) or 10 microg/kg body weight BPA during gestation days 14-18. As adults, the prenatally treated female offspring were time-mated and again fed either corn oil (controls) or the same doses of BPA on gestation days 14-18, resulting in four treatment groups: controls, prenatal BPA exposure, adult BPA exposure, and both prenatal and adult BPA exposure. Maternal behavior was then observed on postnatal days 2-15 and reflex responses were examined in the offspring. Dams exposed to BPA either as fetuses or in adulthood spent less time nursing their pups and more time out of the nest compared with the control group. Females exposed to BPA both as fetuses and in adulthood did not significantly differ from controls. No alterations in postnatal reflex development were observed in the offspring of the females exposed to BPA. The changes seen in maternal behavior may be the result of a direct effect of BPA on the neuroendocrine substrates underlying the initiation of maternal behavior.

Administration, Oral↗