Biomedical subjects

E Alleva

Publications and source records attributed to E Alleva.

138 records · Page 8Linked to original sources

PubMedDate not supplied

Medium and long-term behavioral effects in mice of extended gestational exposure to ozone.

CD-1 mice were continuously exposed to ozone (O3) from 6 days before the formation of breeding pairs to Day 17 of pregnancy. The concentrations used were 0, 0.2, 0.4, and 0.6 ppm; the lowest-observed-effect levels for eye irritation and respiratory function are in the range of 0.08-0.2 ppm for both humans and animals (47). Ozone failed to produce significant effects on either reproductive performance, postnatal somatic and neurobehavioral development (as assessed by a Fox test battery) or adult motor activity (including within-session habituation). In social interaction tests performed in the pre-juvenile period (23-25 days) and the juvenile period (43-45 days), social response endpoints were not modified in O3 mice, but exploration and self-grooming showed concentration dependent effects (decrease and increase, respectively). Performance at 84-98 days in an eight-arm radial maze with water reinforcement was initially impaired in O3 mice, but the results were not entirely consistent; e.g., the data failed to show a concentration dependence of the effects. Overall, the data confirm previous results of an experiment with more limited exposure [pregnancy Days 7-17 (6)] by showing that prenatal O3 exposure, even when extended to include a period before the start of pregnancy and the preimplantation phase, does not produce major or widespread somatic and neurobehavioral effects. Some of the results, however, point to subtle or borderline behavioral deficits which deserve to be considered both in further animal experiments and in the assessment of risk to developing humans.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMedDate not supplied

Early disruption of the mother-infant relationship: effects on brain plasticity and implications for psychopathology.

Early environmental manipulations can impact on the developing nervous system, contributing to shape individual differences in physiological and behavioral responses to environmental challenges. In particular, it has been shown that disruptions in the mother-infant relationship result in neuroendocrine, neurochemical and behavioural changes in the adult organism, although the basic mechanisms underlying such changes have not been completely elucidated. Recent data suggest that neurotrophins might be among the mediators capable of transducing the effects of external manipulations on brain development. Nerve growth factor and brain-derived neurotrophic factor are known to play a major role during brain development, while in the adult animal they are mainly responsible for the maintenance of neuronal function and structural integrity. Changes in the levels of neurotrophic factors during critical developmental stages might result in long-term changes in neuronal plasticity and lead to increased vulnerability to aging and to psychopathology.

Aging↗

PubMedDate not supplied

Prenatal exposure to anti-HIV drugs. long-term neurobehavioral effects of lamivudine (3TC) in CD-1 mice.

The present study was aimed at investigating the long-term effects of prenatal exposure to lamivudine (3TC), an antiretroviral drug used in clinical practice alone or in combination with zidovudine (AZT) to prevent mother-to-child transmission of the HIV virus. Pregnant CD-1 mice were given per os twice daily either 3TC at different doses (125, 250, or 500 mg/kg) or vehicle solution (NaCl 0. 9%) from pregnancy day 10 to delivery. Offspring behavior was examined on postnatal day 35 in a 20-min social interaction test. At adulthood different behavioral endpoints were analyzed, including locomotor activity and exploration in an open field following administration of the muscarinic antagonist scopolamine (2 mg/kg), spatial learning in either radial arm or Morris water maze, virgin female behavior in a maternal induction test, and pain sensitivity in a hot-plate test (52 +/- 0.1 degrees C). Our findings confirm the low neurotoxicity of 3TC in comparison to AZT. However some significant behavioral alterations were found, namely (1) a decrease in immobility in the open field test, (2) an increase in the responsiveness to scopolamine shown by the 500-mg/kg 3TC mice (sniffing behavior) in the open field, and (3) a longer escape latency in the first day of the reversal phase in the Morris task (particularly marked in the 250-mg/kg treatment group). No significant changes in either pain sensitivity, social/affiliative, or maternal behavior were found, although a higher occurrence of aggressive behavior toward foster pups was noted in both 125- and 500-mg/kg 3TC females.

Animals↗

PubMedDate not supplied

Long-term effects of acute perinatal asphyxia on rat maternal behavior.

In this study we used a rat model of graded perinatal asphyxia to study the long-term consequences of this manipulation on rat maternal behavior at adulthood. Rats were delivered by cesarean (C) section and the pups, still in the uterus horns, were placed into a water bath at 37 degrees C for periods of 0 (controls) or 20 min (asphyxia). Subsequently, female pups were given to surrogate mothers, weaned at 21 days postnatally and then left undisturbed until adulthood, when they were mated. Once they gave birth, on postnatal days (Pnds) 1, 3, 5, 7, 9, 11 and 13 they were observed in the home cage five times per day to assess their maternal behavior in an undisturbed condition. In addition, maternal behavior was observed for 30 min in a novel cage on Pnds 4 and 8. Perinatal asphyxia affected maternal behavior in the home cage, hypoxic females being more often found outside the nest area and performing more often behaviors such as self-grooming. Principal component analysis confirmed a more 'active' behavioral profile for hypoxic females. Hypoxic mothers were characterized by a longer latency to perform on-nest behavior and by a reduced frequency of pup retrieval and licking in the novel cage. No significant differences in corticosterone secretion in response to an acute stressor were found in dams belonging to the different treatments or in the body weights of the offspring. These results are suggestive of an arousal deficit due to perinatal hypoxia and point to the dopaminergic system as a potential neurochemical target for an early hypoxic insult.

Age Factors↗

PubMedDate not supplied

Prenatal sulfur dioxide exposure induces changes in the behavior of adult male mice during agonistic encounters.

Sulfur dioxide (SO2) is one of the most important pollutants of the western countries, responsible for several cardiopulmonary diseases in humans. SO2 affects both young and adult people, causing low work productivity with social and economical costs extremely high for the communities. To test whether or not SO2 produces changes in social and/or agonistic behavior of laboratory animals, outbred CD-1 male mice were prenatally exposed to different SO2 concentrations (0, 5, 12, or 30 ppm) up to pregnancy day 14. At adulthood, following a 4-week isolation period, they underwent an aggressive encounter with CD-1 male opponents of the same age, body weight, and isolation condition (single 20-min session). The levels of several responses such as tail rattling, freezing, and defensive postures were reduced by the treatment, particularly during the initial period of the agonistic encounter, whereas offensive and attack behaviors were not significantly modified. In addition, rearing and social investigation increased. Overall, the present results indicate that prenatal SO2 exposure can alter mouse social/agonistic behavior, apparently acting on the approach phase toward the opponent and suggestive of changes in the animals' capability to cope with threatening dangerous situations.

Agonistic Behavior↗

PubMedDate not supplied

Effects of prenatal AZT on mouse neurobehavioral development and passive avoidance learning.

Recent evidence has shown that perinatal administration of zidovudine (AZT) to HIV-infected mothers reduces the risk of maternal-infant transmission of the virus. Treatment of pregnant seropositive women with AZT is becoming a common medical practice, despite the paucity of information about the potential neurotoxic/behavioral-teratogenic effects of AZT on the developing organism. The aim of the present study is to evaluate in mice the short-, medium-, and long-term effects of prenatal exposure to AZT on neurobehavioral development. Pregnant mice were given 0.2, 0.4, and 2.0 mg/ml AZT in drinking water from day 10 of gestation to delivery. Offspring's viability was severely affected in the 2.0 mg/ml AZT group. Thus, behavioral analysis was carried out in offspring of 0.2 and 0.4 mg/ml AZT-treated females only. Some limited but significant alterations were found, such as stunted body weight, delayed appearance of the pole-grasping reflex, and a slight impairment in the acquisition phase of a passive avoidance response. Moreover, sexual differences in some items of the social behavior repertoire appeared to be affected by AZT treatment.

Agonistic Behavior↗

PubMedDate not supplied

Neurobehavioral effects of prenatal lamivudine (3TC) exposure in preweaning mice.

The present study provides a characterization of the behavioral changes induced in preweaning mice by prenatal exposure to lamivudine (3TC), an antiviral drug recently entered in the clinical practice to treat HIV patients. Pregnant CD1 mice were given per os bidaily either 3TC at different doses (125, 250, or 500 mg/kg) or vehicle solution (saline 0.9%) from pregnancy day 10 to delivery. Data on reproductive performance, such as gestation length, litter size, and offspring viability, were collected. Offspring were then examined for a series of different somatic and behavioral end points, including sensorimotor development, ontogenetic pattern of ultrasonic vocalization, passive avoidance learning, and locomotor activity. In the absence of gross changes in somatic and sensorimotor development, a slight change in ultrasound emission was found on postnatal day (PND) 3, with 125 and 500 mg/kg 3TC-treated offspring emitting a lower number of ultrasounds. Learning and retention performances of a passive-avoidance task on PND 20-21 were unaffected by 3TC treatment, while decreased habituation in an automated locomotor activity test was evident in male offspring exposed to 250 and 500 mg/kg 3TC.

Animals↗

PubMedDate not supplied

Neurobehavioral alteration in rodents following developmental exposure to aluminum.

Aluminum (Al) is one of the most abundant metals in the earth's crust, and humans can be exposed to it from several sources. It is present in food, water, pharmaceutical compounds, and in the environment, e.g., as a result of acid rain leaching it from the soil. Exposure to Al has recently been implicated in a number of human pathologies, but it has not yet been definitely proved that it plays a major causal role in any of them. In this paper we review the effects of developmental exposure of laboratory animals to Al salts as a model for human pathological conditions. The data presented show behavioral and neurochemical changes in the offspring of AL-exposed mouse dams during gestation, which include alterations in the pattern of ultrasonic vocalizations and a marked reduction in central nervous system (CNS) choline acetyltransferase activity. Prenatal Al also affects CNS cholinergic functions under Nerve Growth Factor (NGF) control, as shown by increased central NGF levels and impaired performances in a maze learning task in young-adult mice. The need for more detailed studies to evaluate the risks for humans associated with developmental exposure to Al, as well as the importance of using more than one strain of laboratory animal in the experimental design, is emphasized.

Administration, Oral↗

PubMedDate not supplied

Methodological analysis in behavioral toxicology: an ethotoxicological approach.

A constraint in the development of laboratory animal models of human disease conditions is their applicability to the natural environment in which a given animal species evolved. The range of behavioral patterns that can be carefully assessed and quantified in the laboratory is sometimes limited. Although field studies reflect behavioral responses in natural settings, they may also have methodological limitations. Laboratory techniques are not applicable to wild species since natural conditions cannot be brought into a laboratory in an inexpensive or reliable way. However, it is possible to create near-natural settings which may not fulfill all the criteria of the actual context of evolution, but which can be controlled by the experimenter. We recommend an integrative style of approach considering laboratory constraints and, at the same time, the ecological niche in which a given behavioral pattern evolved. This type of ethological assessment may be useful when carrying out toxicological studies on both wild and laboratory mammals.

Animals↗

PubMedDate not supplied

An updated role for nerve growth factor in neurobehavioural regulation of adult vertebrates.

Increasing attention has been focused on the role(s) of nerve growth factor (NGF) in neurobehavioural regulations of adult vertebrates. This interest springs from the emerging evidence that NGF is a "regulator" of physiological processes belonging to the three main homeostatic systems: the nervous, immune and endocrine systems. In fact, the spectrum of action of the NGF molecule is not restricted to neuronal cell types (central basal forebrain; peripheral sensory and sympathetic neurons) but extends also to nonneuronal cells. In mice intermale aggressive behaviour enhances serum NGF levels and promotes its synthesis in some hypothalamic areas. Other types of social events are able to cause NGF release, particularly under stress conditions. The achievement of a social role (dominant vs subordinate) is due to a functional loop involving salivary NGF release-->enhanced production of adrenal hormones-->submissive behaviour-->NGF release. In humans, plasma platelet-derived growth factor (PDGF) increases following mental stress. The aim of this review is to give an updated survey on NGF roles in neurobehavioural regulations of adult animals.

Animals↗

PubMedDate not supplied

Genetic and temporal determinants of pesticide sensitivity: role of paraoxonase (PON1).

Susceptibility to organophosphorus (OP) insecticides and nerve agents is strongly influenced by genetic and developmental factors. A number of organophosphorothioate insecticides are detoxified in part via a two-step pathway involving bioactivation of the parent compound by the cytochrome P450 systems, then hydrolysis of the resulting oxygenated metabolite (oxon) by serum and liver paraoxonases (PON1). Serum PON1 has been shown to be polymorphic in human populations. The Arg192 isoform (PON1R192) of this HDL-associated protein hydrolyzes paraoxon (POX) at a high rate, while the Gln192 isoform (PON1Q192) hydrolyzes paraoxon at a low rate. The effect of the polymorphism is reversed for the hydrolysis of diazoxon (DZO), soman and particularly sarin. Phenylacetate is hydrolyzed at approximately the same rate by both PON1 isoforms and chlorpyrifos oxon (CPO) slightly faster by the PON1R192 isoform. In addition to the effect of the amino acid substitution on rates of toxicant hydrolysis, two other factors influence these rates. The expression of PON1 is developmentally regulated. Newborns have very low levels of PON1. Adult levels in rats and mice are reached at 3 weeks of age and in humans, sometime after 6 months of age. In addition, among individuals of a given genotype, there is at least a 13-fold difference in expression of PON1 that is stable over time. Dose/response experiments with normal mice injected with purified PON1 and with PON1 knockout mice have clearly demonstrated that the observed differences of in vitro rates of hydrolysis are significant in determining differential sensitivities to specific insecticides processed through the P450/PON1 pathway. Injection of purified rabbit PON1 protects mice from cholinesterase inhibition by chlorpyrifos (CPS) and CPO. Knockout mice are much more sensitive to CPO and DZO than are their PON1+/+ littermates or wild-type mice. A number of recent reports have also indicated that the PON1R192 isoform may be a risk factor for cardiovascular disease. Studies with PON1 knockout mice are also consistent with a role of PON1 in preventing vascular disease.

Animals↗

PubMedDate not supplied

The Acomys cahirinus (spiny mouse) as a new model for biological and neurobehavioural studies.

Acomys cahirinus is a precocial murid and a comparison of its development with altricial species of the same family, such as the rat and mouse, may shed some light on the relationship between genetic and environmental factors in the development. The use of Acomys in neurobehavioural studies and its comparison with mouse and rat may be particularly profitable. Behavioural, differences particularly in the exploratory behaviour, are paralleled by differences in the brain anatomy. Therefore Acomys seems to be a new very promising tool for investigating neurological and behavioural developmental systems.

Animals↗