Biomedical subjects

D Santucci

Publications and source records attributed to D Santucci.

At least 19 recordsLinked to original sources

PubMed2006

Organochlorine and heavy-metal contaminants in wild mammals and birds of Urbino-Pesaro Province, Italy: an analytic overview for potential bioindicators.

Tissue samples from 56 bird and 11 mammal species of different trophic levels, collected from 1994 to 1995 from the Urbino-Pesaro area in the Marche region of central Italy, were analyzed for the presence of organochlorine compounds (polychlorinated biphenyls and p,p'-DDE) and heavy metals (Pb, Cd, Cr, and Hg). Results revealed interspecies differences in pollutant residue concentrations. A clear relationship between contaminant and trophic levels emerged depending on several factors specific to the chemicals and the organisms, the importance of dietary accumulation, and metabolic capacity as it increased toward higher trophic levels. Polychlorinated biphenyls and p,p'-DDE were found in all of the bird and mammal species analyzed (bird- or fish-eating birds), and insectivore mammals showed the highest level of these contaminants. Pb and Hg residues were also widely detected and reflected trophic-level differences. The highest concentration of Pb was found in herbivorous or bird-eating aquatic invertebrates and in insectivorous mammals, particularly in the hedgehog (Erinaceus europaeus), whereas the highest Hg levels were found in fish-eating birds. All of the other heavy metals were detected at low concentrations and represented background levels for birds and mammals, with the exception of increased amounts of Cd and Cr, respectively, found in stone marten (Martes foina) and fox (Vulpes vulpes). Data from this study provided information on baseline levels of interest to monitor status and trends in chemical residue in biota in this specific area, and therefore they represent a tool to evaluate potential ecologic, wildlife, and human health exposure.

Adipose Tissue↗

PubMed2005

The endocrine disruptor atrazine accounts for a dimorphic somatostatinergic neuronal expression pattern in mice.

It has now been established that a large number of man-made and natural chemicals are capable of interfering with the action of natural hormones. In this category "endocrine disruptors" such as the herbicide atrazine, when administered at ecological low doses (1 or 100 microg/kg per day) from gestational day 14 to postnatal day 21, provided a clear dimorphic neurodegenerative pattern in some brain areas of the domestic mouse (Mus musculus). Indeed, the high concentration (100 microg/kg per day) with respect to the low concentration (1 microg/kg per day) induced relevant neuronal damage in extrahypothalamic sites, such as the cortical and striatal areas in both sexes. Marked alterations in other areas, including the hippocampal and hypothalamic nuclei, were mostly typical of the female. At the neuronal level, the neuropeptide somatostatin, specific for the secretion of growth hormone, seemed to be a major target of atrazine effects, as demonstrated by evident subtype2,3,5 receptor mRNA differences of this neuropeptide, at least for the first two subtypes. In particular, a very strong (p < 0.001) upregulation of subtype2 expressing neurons was detected in female hypothalamic areas, specifically the suprachiasmatic nucleus, whereas a similar downregulatory trend was reported for some extrahypothalamic areas such as the striatum. Interestingly, very strong upregulatory and downregulatory actions were detected for neurons expressing subtype3 in male hypothalamic and amygdalar regions and in the cortical and hippocampal areas, respectively. Overall, it appears that these first neurotoxicological effects of atrazine are very likely linked to dimorphic expression patterns of specific somatostatin subtypes in discrete but key hypothalamic and extrahypothalamic areas of Mus musculus.

Animals↗

PubMed2001

Ultrasonic vocalisation emitted by infant rodents: a tool for assessment of neurobehavioural development.

Ultrasonic vocalisations (USVs) emitted by altricial rodent pups are whistle-like sounds with frequencies between 30 and 90 kHz. These signals play an important communicative role in mother-offspring interaction since they elicit in the dam a prompt response concerning caregiving behaviours. Both physical and social parameters modulate the USV emission in the infant rodent. Recently, a more detailed analysis of the ultrasonic vocalisation pattern, considering the spectrographic structure of sounds has allowed a deeper investigation of this behaviour. In order to investigate neurobehavioural development, the analysis of USVs presents several advantages, mainly: (i) USVs are one of the few responses produced by very young mice that can be quantitatively analysed and elicited by quantifiable stimuli; (ii) USV production follows a clear ontogenetic profile from birth to PND 14-15, thus allowing longitudinal neurobehavioural analysis during very early postnatal ontogeny. The study of this ethologically-ecologically relevant behaviour represent a valid model to evaluate possible alterations in the neurobehavioural development of perinatally treated or genetically modified infant rodents. Furthermore, the role played by several receptor agonists and antagonists in modulating USV rate makes this measure particularly important when investigating the effects of anxiogenic and anxiolytic compounds, and emotional behaviour in general.

Animals↗

PubMed2001

Effect of hypergravity on the mouse basal expression of NGF and BDNF in the retina, visual cortex and geniculate nucleus: correlative aspects with NPY immunoreactivity.

We investigated the effect of hypergravitation on Nerve growth factor (NGF) and Brain-derived-neurotrophic factor (BDNF) expression in the visual cortex, geniculate nucleus (GN), and retina of adult male mice. The results showed that altered gravity causes an increase in NGF and BDNF in the visual cortex and GN which resulted to be associated with an up-regulation of cells immunoreactive to neuropeptide Y (NPY) in the visual cortex and GN. We also found a decrease in NGF, BDNF, and NPY in the mouse retina exposed to hypergravity. These findings suggest that alteration in gravitational environment differentially affects local neurotrophic factors and NPY expression. The possible functional significance of these observations is discussed.

Animals↗

PubMed2001

Prolonged exposure to low doses of ozone: short- and long-term changes in behavioral performance in mice.

Two separate experiments were designed to assess the effects of ozone exposure on outbred CD-1 mice. In the first experiment, adult males were exposed continuously to O3 at 0, 0.3, or 0.6 ppm for 30 days and their behavior was assessed in a 5-min open-field test on exposure days 4 and 19 and on day 3 after the end of the exposure phase. In addition, mice performed a Morris water maze task from exposure day 24 to 28. In the second experiment, adult females were exposed from 30 days prior to the formation of breeding pairs until gestational day 17 to the same doses used in the first experiment. Litters were fostered at birth to untreated dams and neurobehavioral development of the offspring was investigated until adulthood. Specifically, somatic and sensorimotor development [postnatal day (PND) 2-20], homing performance (PND 12), motor activity (PND 21), passive avoidance (PND 22-23), water maze performances (PND 70-74), and response to a nociceptive stimulus (PND 100) were assessed. Results from both experiments confirm that exposure to O3 slightly but selectively affected neurobehavioral performance in rodents. Exposure to O3 did not grossly affect neurobehavioral development, whereas it consistently impaired reversal learning in the Morris water maze test in both prenatally and adult exposed mice. Moreover, longer latency to step-through in the first trial of the passive avoidance test and a decrease in wall rearing in the hot-plate test were recorded in O3 prenatally exposed mice. Except for the first open-field test, altered responses were observed only in animals exposed at the intermediate concentration of the gas. Adaptation and/or onset of compensatory mechanisms might be responsible for the lack of linear dose-response relationships.

Adaptation, Physiological↗

PubMed2001

Psychosocial vs. "physical" stress situations in rodents and humans: role of neurotrophins.

Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are well-studied polypeptide growth factors involved in the development and maintenance of specific peripheral and central populations of neuronal cells. In addition to its role as a neurotrophic agent, NGF controls very complex functions in vertebrate physiology. A variety of cells outside the nervous system are in fact able to synthesize NGF including epithelial cells, fibroblasts, lymphocytes, and macrophages. NGF target cells have been identified in the nervous, immune, and endocrine systems, suggesting that NGF may operate through multiple paths to ultimately regulate physiological homeostasis and behavioral coping. We used a mouse model of social stress to demonstrate that NGF levels increase both in plasma and in the hypothalamus following intermale aggressive interactions. The investigation has been extended to other species, including humans, to show that labour, lactation, and the anticipation of the first jump with a parachute also result in increased NGF plasma levels and in changes in the distribution of NGF receptors on lymphocytes. BDNF activation is caused by both physical and social stress events. The aim of this review is to (1) outline the current understanding of the roles of NGF and BDNF in stress-related physiological changes in vertebrates, in particular for physical vs. psychological stressors, which may activate both similar and different neurobiological pathways, and (2) summarize recent efforts to derive pharmacological strategies from the increasing body of BDNF and NGF neurobehavioral data.

Animals↗

PubMed2001

Response of CD-1 mice to the chemical defence of a common arthropod (Ommatoiulus sabulosus).

In order to set up a novel and ethologically relevant methodology that could be applied to the study of olfactory capabilities in transgenic mice, we analysed the behavioural responses of sexually mature male and female CD-1 mice individually exposed to a striped millipede, Ommatoiulus sabulosus (L.), a very common myriapod species that secretes a repulsive and persistent odour in the presence of a predator. As control, we exposed mice to a larva of the lepidopteran Greater wax moth, Galleria mellonella (L.), which closely resembles the millipede in shape and dimensions but which does not secrete a repulsive odour in defence. We recorded and analysed a wide spectrum of behavioural responses including both those of avoidance and nonavoidance such as attempts to eat the arthropod. Behavioural responses were measured for 10 min upon first exposure to the millipede or wax moth. The procedure was repeated for 3 consecutive days. Upon exposure to a millipede, mice of both sexes showed a dramatic increase in the avoidance behaviour of digging. Moreover, millipedes were repulsive to mice and though they were sniffed frequently and sometimes caught, they were never eaten. In comparison, mice exposed to a wax moth almost always ate it. Sex differences emerged only for locomotion with female appearing to be more active. These results suggest that mice are able to discriminate between ethologically relevant odours and that the behavioural responses they display in this more natural context differ from those observed in response to odours of predators.

Animals↗

PubMed2000

Neurobehavioural effects of hypergravity conditions in the adult mouse.

To evaluate the behavioural response to a hypergravity condition in CD-1 mice, young adult subjects of both sexes were exposed to 2 g for a single 60 min rotational session. Motion sickness (MS) and ethological-type scoring of different activities were used to evaluate the behavioural response. Nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) levels were also assessed. Behavioural scores indicated a transient mild sickness associated with hypergravity, with reduction in spontaneous activity. In males kaolin consumption (a MS index) increased following rotation while females consumed more kaolin irrespective of whether they have been rotated or simply exposed to the noise and vibration of the rotational apparatus. In males, hypothalamic NGF levels were markedly increased after rotation while no major changes were observed in central BDNF expression. These results indicate mice may represent a suitable MS model.

Animals↗

PubMed1999

Behavioural effects of endocrine disrupting chemicals on laboratory rodents: statistical methodologies and an application concerning developmental PCB exposure.

Appropriate behavioural tests and adequate statistical tools may help to establish the ED properties of a given compound by pointing out the alterations of selected behavioural endpoints. Frequently, laboratory collected data consist of frequencies and/or durations of specific items, and the analysis of variance (ANOVA) technique is performed to assess whether the investigated factors affect these behavioural endpoints. Moreover, when numerous aspects of behaviour are investigated simultaneously, Principal Component Analysis (PCA), a multivariate technique, may be very useful to reduce the overwhelming number of correlated original variables to a few orthogonal artificial variables (factors). Continuous Time Markov Chain (CTMC) models may be applied to analyse the time structure of a behavioural pattern when data consist of sequences of events and the time points at which they occur. Moreover, the Cox Proportional Hazard Model, a methodology originally developed for the analysis of failure time data, may help to evidence the effects of a given treatment on behavioural sequences when the assumptions of CTMC models are not fully satisfied. Analyses on data from mice of the outbred CD-1 strain (controls in a study of toxicity and exposed to PCB during development) are presented as examples to show how adequate statistical analyses and appropriate behavioural tests may reveal relevant effect of treatments otherwise not easily detected.

Animals↗

PubMed1999

Ultrasonic vocalizations elicit orienting and associative reactions in preweanling mice.

On postnatal days (PND) 12 and 13, 90 male Swiss CD-1 mice were tested for orientation to 3 intensities of recorded ultrasounds while climbing an inclined wire grid surface. Motor responses and vocalization to replayed ultrasounds (55-75 kHz) of 20-, 40-, and 60-dB SPL indicated an intensity dependence. In Experiment 2, 138 pups were exposed to either contingent or noncontingent pairings of recorded ultrasounds of 55-75 kHz, averaging 40 dB, and mild inescapable footshocks, or taped vocalizations or footshocks only on PND 12, 14, or 16. At PND 18, subjects were tested for passive avoidance following exposure to the taped ultrasounds only upon entry into the dark side of a black-white compartment. Results suggested only overall, nonspecific effects of pretreatment to elicit responses antagonistic to motor activity. In Experiment 3, 36 pups at PND 15 were tested for passive avoidance with the ultrasound recordings of 40- or 80-dB onset upon entry to the dark compartment; a third group had no ultrasound exposure. A significant intensity effect confirmed that the ultrasounds had prepotent properties.

Animals↗

PubMed1998

Ultrasonic vocalizations by infant laboratory mice: a preliminary spectrographic characterization under different conditions.

During the first 2 to 3 weeks of life, isolated neonatal mice emit ultrasonic vocalizations, with various conditions such as hypothermia or olfactory or tactile stimulation eliciting this behavior. Although it is known that pup vocalizations stimulate prompt expression of maternal behavior, the communicative role of infant ultrasonic calls is still a matter of investigation. A fine-grained spectrographic analysis of ultrasonic calls emitted by pups exposed to different conditions was performed. Forty 8-day-old outbred CD-1 mice (Mus musculus) were isolated from their mothers and littermates and randomly exposed to one of the following conditions: (a) odor from the nest, (b) social isolation, (c) low temperature-isolation, (d) tactile stimulation, or (e) odor from a conspecific adult male. Upon consideration of the spectrogram typology and emission frequency interval, it appears that the conditions under which vocalizations are emitted influence the sound characteristics of call production.

Analysis of Variance↗

PubMed1996

Developmental abnormalities and age-related neurodegeneration in a mouse model of Down syndrome.

To study the pathogenesis of central nervous system abnormalities in Down syndrome (DS), we have analyzed a new genetic model of DS, the partial trisomy 16 (Ts65Dn) mouse. Ts65Dn mice have an extra copy of the distal aspect of mouse chromosome 16, a segment homologous to human chromosome 21 that contains much of the genetic material responsible for the DS phenotype. Ts65Dn mice show developmental delay during the postnatal period as well as abnormal behaviors in both young and adult animals that may be analogous to mental retardation. Though the Ts65Dn brain is normal on gross examination, there is age-related degeneration of septohippocampal cholinergic neurons and astrocytic hypertrophy, markers of the Alzheimer disease pathology that is present in elderly DS individuals. These findings suggest that Ts65Dn mice may be used to study certain developmental and degenerative abnormalities in the DS brain.

Aging↗

PubMed1994

Early exposure to aluminium affects eight-arm maze performance and hippocampal nerve growth factor levels in adult mice.

Aluminium has been implicated in the etiology of several human pathologies but, to date, little attention has been given to the potential damage caused by gestational exposure to aluminium or to any long-term effect of early exposure. Aluminium sulphate (200 mg/kg) was administered intraperitoneally to pregnant female mice (days 10 to 13 of gestation), and male progeny was assessed in a radial eight-arm maze task at 70 days (20 daily sessions, 50 microliters water as reward). Overall, aluminium-exposed mice performed less efficiently in the radial maze than the vehicle-exposed animals. Neurobiological data showed that aluminium mice also had a higher level of nerve growth factor in the hippocampal formation when compared to controls.

Aluminum↗

PubMed1994

Behavioral and hormonal responses to stress in the newborn mouse: effects of maternal deprivation and chlordiazepoxide.

These studies investigated behavioral and hormonal responses to stress in developing mice. Experiment 1 examined the effects of 24-hr maternal deprivation on corticosterone (CORT) secretion and ultrasonic vocalization (UVZ) rate in 4-, 8-, and 12-day-old mice. At these ages, exposure to a novel environment resulted in minimal changes in CORT secretion. Maternal deprivation increased pups' CORT secretion in an age-dependent fashion but did not affect their UVZ rate. The aim of experiment 2 was to test the effects of chlordiazepoxide (CDP), an anxiolytic compound, on CORT secretion and UVZ in both normally reared and in maternally deprived 8-day-old mice. CDP administration elevated CORT secretion in a dose-dependent fashion, producing larger CORT increases in deprived (DEP) animals. CDP affected UVZ only in nondeprived (NDEP) animals: UVZ rate was decreased by high CDP doses. Overall, these findings demonstrate that the infant mouse shows a period of stress hyporesponsiveness similar to the rat and that maternal presence contributes to inhibit adrenocortical activity. CDP administration, but not novelty exposure, increased CORT secretion in 8-day-old normally reared mice suggesting that during the stress hyporesponsive period, the HPA axis is capable of responding only to specific stimuli. Changes in HPA axis activity and UVZ rate resulting from maternal deprivation and/or CDP challenge do not seem to be directly related.

Animals↗

PubMed1994

IGF-I and IGF-I24-41 but not IGF-I57-70 affect somatic and neurobehavioral development of newborn male mice.

Insulin-like growth factor (IGF-I) is a trophic factor for both neurons and glial cells. Its presence in developing and adult nervous system suggests an important role for this peptide in the development of neural circuitries. Neonatal male mice of the CD-1 outbred strain were injected intracerebroventricularly with either recombinant IGF-I, synthetic IGF-I fragment 24-41 or IGF-I fragment 57-70 on postnatal days (PND) 2, 4, and 7. Physical traits such as body weight gain, body length, and tail length were recorded daily from PND2 to PND13. Sensorimotor development was scored according to a modified Fox's scale. The ultrasonic vocalization pattern on PND8 and homing performance on PND10 were also recorded. Measures for body weight gain and tail length of the pups were significantly increased following treatment with the whole IGF-I peptide. However, neither IGF-I nor the smaller fragments affected mice sensorimotor development. IGF-I and IGF-I24-41 but not IGF-I57-70 increased the rate of ultrasonic calls of the pups measured on PND8. These data provide evidence that IGF-I regulates somatic growth and behavioral development when administered in newborn mice and that different portions of the peptide can exert different effects.

Animals↗

PubMed1994

Effects of acute and continuous ozone (O3) exposure on activity/exploration and social behavior of CD-1 mice.

This study was aimed at investigating the behavioral effects of ozone (O3) exposure in CD-1 mice. Pairs of same-sex adult male and female mice were continuously exposed for 13 days to either 0, 0.4, 0.8, or 1.2 ppm O3. The exposure apparatus consisted of a system for O3 production and delivery into four stainless-steel chambers, each equipped to contain up to 24 home cages, with continuous monitoring and recording of concentrations. Acute behavioral changes were assessed during the first hour of O3 exposure without removing animals from the chambers. The onset of exposure produced remarkable behavioral disturbances consisting of a sharp increase of several responses (rearing, sniffing, grooming, feeding, and social interactions) paralleled by a reduction of bar-holding. These changes were rapidly reversed within 1 hour, suggesting that they constituted a response to strong novel stimulation followed by habituation. Subsequently, brief sessions of videorecording of the animals' activities in freshly cleaned cages (identical to the home cages) were performed outside the chambers after 3, 7, and 10 days of exposure. These tests showed a significant concentration-dependent increase of grooming and rearing and a decrease of crossing and wall climbing. Both food and water intake showed a nonmonotonic trend over time consisting of a concentration-dependent depression (for about 3 and 7 days, respectively) followed by recovery; body weight followed a similar trend. The detailed study of various components of the animal's behavioral repertoire, showing concentration-dependent and time-dependent changes in different directions, appears to be a sensitive tool in the analysis of pollutants' effects.

Air Pollutants↗

PubMedDate not supplied

Neonatal exposure to bFGF exerts NGF-like effects on mouse behavioral development.

Brain cells are naturally exposed to a variety of trophic factors during development. Basic Fibroblast Growth Factor (bFGF), a protein found in the central nervous system (CNS) enhances both survival and proliferation of several CNS cell lines. Neonatal mice of the CD1 outbred strain were injected intracerebroventricularly (ICV) with bovine bFGF on postnatal days 2, 4, and 7. bFGF, dissolved in 25 microliters of saline, was given in the 1, 5, 25, and 1000 ng doses. Physical traits such as body weight gain, body length, and tail length were recorded from postnatal day (PND) 2 to PND 12. Neurobehavioral development was scored according to a modified Fox's Scale. The ultrasonic vocalization pattern (PND 8), homing performance (PND 10), open-field activity and exploration of a novel object (PND 18) were also assessed. Pups receiving 25 and 1000 ng doses of bFGF showed a slight but significant acceleration in the appearance of some early sensorimotor reflexes, such as weak and tactile stimulation, forelimb placing and grasping, and screen climbing, during the first postnatal weeks. The other responses were less affected or not affected at all. Data are compared with similar systemic exposure of neonatal mice to Nerve Growth Factor (NGF).

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↗