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E Alleva

Publications and source records attributed to E Alleva.

At least 19 recordsLinked to original sources
PubMed2002

Stress and nerve growth factor: findings in animal models and humans.

Stress is elicited by environmental, social or pathological conditions occurring during the life of animals and humans that determine changes in the nervous, endocrine and immune systems. In the present review, we present data supporting the hypothesis that stress-related events both in animal models and humans are characterized by modifications of endogenous nerve growth factor (NGF) synthesis and/or utilization. Stress inducing alteration in NGF synthesis and/or utilization appears to be more severe during neurogenesis and in early postnatal life. However, NGF endogenously released during stress may promote remodeling of damaged tissues following acute and/or chronic stressful events.

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

Prenatal exposure to anti-HIV drugs: neurobehavioral effects of zidovudine (AZT) + lamivudine (3TC) treatment in mice.

BACKGROUND: The new antiretroviral treatments that combine the zidovudine (AZT) regimen with lamivudine (3TC) appear as a cost-effective alternative to the current AZT monotherapy to prevent mother-to-fetus transmission of the HIV-1 virus. Recent evidence in uninfected children raised concern about the long-term effects of perinatal exposure to AZT and 3TC, especially when used in combination. Animal studies indicated behavioral changes in offspring exposed perinatally to both AZT and 3TC, whereas no animal data are available on the effects of the perinatal exposure to the AZT + 3TC combination on neurodevelopment. METHODS: Pregnant CD-1 mice received p.o. AZT + 3TC (160 and 500 mg/kg, respectively) or vehicle solution (NaCl 0.9%) twice daily from gestational day 10 to delivery. Maternal reproductive endpoints such as pregnancy length, abortion, litter size, sex ratio, and offspring viability were assessed. Pups were scored for different somatic and behavioral endpoints, including sensorimotor development, homing performance on postnatal day (PND) 10, passive-avoidance testing (PND 22-23), locomotor activity (PND 23), and social interaction (PND 35). RESULTS: While no effects were observed on maternal reproductive endpoints, treated pups showed a long-lasting reduction of body weight and a slightly delayed maturation of placing and grasping reflexes and pole grasping. No effects on passive-avoidance or locomotor activity were found. AZT + 3TC-treated mice showed selective alterations in the social interaction test; the treated female offspring also displayed a significant reduction of affiliative interactions. CONCLUSIONS: The combination of AZT and 3TC (1) induced small, but more marked, effects on somatic and sensorimotor development than either of these drugs administered separately; and (2) affected juvenile social behavior.

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

Prenatal AZT or 3TC and mouse development of locomotor activity and hot-plate responding upon administration of the GABA(A) receptor agonist muscimol.

RATIONALE: Zidovudine (AZT) and lamivudine (3TC) are nucleoside analogues administered prenatally in clinical practice, separately or in combination, as antiretroviral drugs to prevent HIV mother-to-child transmission by inhibiting viral reverse transcriptase. In animal studies pre- and/or perinatal exposure to AZT and 3TC induce age- and sex-dependent neurobehavioural alterations in the offspring. OBJECTIVE: Investigation of short- and medium-term effects of in utero exposure to AZT or 3TC on development of the GABAergic system. METHODS: Pregnant CD-1 mice were given orally twice daily AZT (160 mg/kg), 3TC (500 mg/kg) or vehicle solution (NaCl 0.9%) from pregnancy day 10 to delivery. Offspring locomotion and nociceptive sensitivity were examined on postnatal day (pnd) 8, 14, and 28 after administration of two doses of GABAergic agonist muscimol (pnd 8 and 14: 0.05 and 0.2 mg/kg; pnd 28: 0.2 and 1.0 mg/kg). A 30-min locomotor activity test and a 60 s hot-plate test (50+/-1 degrees C) were used. RESULTS: AZT and 3TC treated mice showed a mild increase of locomotor activity after administration of the high dose muscimol on pnd 8. On pnd 14 the low muscimol dose enhanced locomotor activity in vehicle and 3TC, but not in AZT pups, whereas no prenatal treatment effect was evident on pnd 28. AZT increased nociceptive sensitivity at all ages considered. CONCLUSIONS: Prenatal AZT effects on locomotor activity appear clearly detectable after GABAergic challenge and seem to be transient. AZT effects on pain sensitivity did not appear to be dependent on GABA regulated nociceptive mechanisms. Prenatal 3TC exposure had rather limited effects on locomotor activity development, and no effect on nociception.

Animals↗
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

NGF expression in the developing rat brain: effects of maternal separation.

A number of studies have shown that mothering style in rodents can produce neuroendocrine, neurochemical and behavioural changes in the adult, although the basic mechanisms initiating this cascade of events still need to be investigated. Long term changes in neuronal function might be due to alterations in the expression of neurotrophins which have been shown to promote neuronal survival, differentiation and function during development, such as Nerve Growth Factor (NGF). NGF is essential for proper development of sympathetic and neural crest-derived sensory neurons of the peripheral nervous system as well as of central cholinergic neurons. In previous studies, using a maternal separation paradigm, we have shown that NGF expression is increased in the dentate gyrus and the hilus of the hippocampus as a result of brief (45 min) maternal separations. In the present study neonatal rats were separated for longer periods of time (up to 3 h) and at different ages during development (9 and 16 days postnatally). Results indicate that the effects of maternal separation on NGF expression are stronger with longer separations and are not restricted to the hippocampal region but can be seen also in other brain areas. Overall these results indicate that external factors, such as the presence/absence of the mother, can modify neurotrophic factor's availability in the brain, thus indicating NGF as a potential player in environmentally-mediated brain plasticity during development.

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↗
PubMed2000

Intracerebroventricular administration of brain-derived neurotrophic factor in adult rats affects analgesia and spontaneous behaviour but not memory retention in a Morris Water Maze task.

The present study tested the effects of in vivo administration of brain-derived neurotrophic factor (BDNF) and of its antibody (anti-BDNF) in a Morris Water Maze (MWM) task. Adult male rats were trained for three days in a MWM. At the end of the last training trial, subjects were injected intracerebroventricularly with one of the following: (i) BDNF (24 microg); (ii) anti-BDNF (25 microg); or (iii) vehicle (PBS, injection volume 10 microl). On day 5, subjects were tested for memory retention, pain sensitivity and locomotor behaviour. No differences emerged in the MWM as a function of treatment, even with a reduced number of acquisition trials. Nonetheless, BDNF affected both pain threshold in the hot-plate test, as well as exploratory behaviour in the open field test.

Animals↗
PubMed2000

Prolonged perinatal exposure to AZT affects aggressive behaviour of adult CD-1 mice.

RATIONALE: AZT is commonly administered to seropositive women and their neonates to prevent mother-to-child transmission of HIV. Recently, animal studies performed in monkeys and rodents have revealed that pre- and/or perinatal exposure to AZT induces age- and sex-dependent behavioural alterations in the offspring, possibly resulting from an action of this drug on CNS targets. Long-term effects of prenatal AZT treatment on social/aggressive behaviour of adult male mice have been previously described. Specifically, AZT has been shown to induce selective changes in the offensive components of agonistic interactions. OBJECTIVE: The aim of the present study was to extend previous findings, analysing the long-term effects of a more prolonged AZT exposure on intraspecific male mice agonistic behaviour. METHODS: AZT was given orally twice daily to pregnant CD- mice. The dosage selected for AZT was 160 mg/kg. Saline solution (0.9% NaCl) was used as vehicle. Starting on postnatal day (PND) 60 isolated males underwent five 15-min repeated encounters with an opponent of the same age and strain isolated for the same amount of time. Furthermore, a locomotor activity test (PND 67) and a hot-plate test (52 +/- 0.1 degrees C) (PND 74) were performed to assess AZT effects on, respectively, general activity and pain sensitivity. RESULTS: AZT perinatal exposure reduced attack behaviour of adult mice, while increasing the likelihood of them behaving as subordinates. Furthermore, long-term effects of AZT treatment on pain sensitivity were found in the hot-plate test, with AZT mice showing higher pain thresholds than controls. CONCLUSIONS: Overall, these data indicate that perinatal exposure to drugs such as AZT exerts selective effects on the developing CNS, resulting in long-term behavioural disturbances. Future studies will need to address the issue of the specific mechanisms underlying these effects.

Aggression↗
PubMed2000

Effects of prenatal AZT+3TC treatment on open field behavior and responsiveness to scopolamine in adult mice.

Treatment of pregnant seropositive women and their neonates with the nucleoside analogs (reverse transcriptase inhibitors) zidovudine (AZT), lamivudine (3TC) and their combination has become a standard of care in industrialized countries to prevent transmission of the HIV-1 virus. Animal studies indicated limited but significant behavioral changes in AZT or 3TC-prenatally exposed offspring, whereas data on the potential neurobehavioral outcomes of AZT+3TC combination are still lacking. The aim of the present study was to assess in mice prenatally exposed to AZT+3TC the functional state of cholinergic muscarinic neuroregulation at adulthood. Pregnant CD-1 mice received per orem twice daily AZT+3TC (160 and 500 mg/kg, respectively) or vehicle solution (NaCl 0.9%) from gestational day (GD) 10 to delivery (GD 19). Locomotor activity, exploratory behavior and responsiveness to the muscarinic cholinergic blocker scopolamine (2 mg/kg) were analyzed at adulthood (PND 70) in offspring of both sexes in an open field test. Results indicated that prenatal AZT+3TC exposure does not influence responsiveness to the muscarinic cholinergic antagonist as measured by analysis of the drug's effects on locomotor and exploratory activity and different behavioral items. However, AZT+3TC-treated mice displayed higher frequency of rearing, and lower frequency and duration of self-grooming behavior, consistent with an effect on dopaminergic neurotransmission. However, this would need confirmatory experiments.

Animals↗
PubMed2000

Learning performances, brain NGF distribution and NPY levels in transgenic mice expressing TNF-alpha.

Tumor necrosis factor-alpha (TNF-alpha) is a cytokine involved in a variety of neurobiological activities including changing behavior and regulation of both neurotrophin and neuropeptide levels. In this study we used two lines of transgenic mice overexpressing brain TNF-alpha characterized by neurological deficits (line Tg6074) or phenotypically normal (line TgK3). We analyzed whether or not impairments in learning and memory processes due to TNF-alpha overexpression were associated with changes in endogenous brain NGF, NPY and beta-amyloid. The results indicate that full TNF-alpha transgene expression disrupted the learning capabilities of transgenic mice (both Tg6074 and TgK3). NGF decreased in the hippocampus of both transgenic mice whereas hippocampal NPY slightly potentiated in Tg6074. The decrease in NGF is correlated with deficits in spatial learning and memory whereas inflammation in the brain of Tg6074 could be responsible of the hippocampal increase in NPY. As a whole, these results show that transgenic mice overexpressing TNF-alpha in the brain represent a useful model for studying neuronal degeneration and brain inflammatory processes.

Amyloid beta-Peptides↗
PubMed2000

Serum NGF levels in children and adolescents with either Williams syndrome or Down syndrome.

The neurotrophin nerve growth factor (NGF) is a major regulator of peripheral and central nervous system development. Serum NGF was measured in normally developing control children (n=26) and in individuals affected by congenital syndromes associated with learning disability: either Williams syndrome (WS; n=12) or Down syndrome (DS; n=21). Participants were assessed at three distinct developmental stages: early childhood (2 to 6 years), childhood (8 to 12 years), and adolescence (14 to 20 years). A sample was taken only once from each individual. Serum NGF levels were markedly higher in participants with WS, than DS and control participants. In addition, different developmental profiles emerged in the three groups: while in normally developing individuals NGF levels were higher in early childhood than later on, children with WS showed constantly elevated NGF levels. When compared to control participants, those with DS showed lower NGF levels only during early childhood. Neuropsychological assessment confirmed previously reported differences among the three groups in the development of linguistic/cognitive abilities. Some features of individuals with WS, such as hyperacusis and hypertension, could be related to high-circulating NGF levels.

Adolescent↗
PubMed2000

Important hints in behavioural teratology of rodents.

The paper deals with the most important items regarding the improvement of quality of experimental procedures when testing drug effects on behaviour and development of commonly-used rodent species. Current-used test procedures for immature and adult rodents exposed early developmentally are briefly described and recent advances and difficulties in their hands-on interpretation are highlighted. Comparability of measures in human and animals for drug-effect assessment is also shortly discussed. It is then stressed that studies on rodents carried out in seminaturalistic and naturalistic settings may offer a highly profitable direction for future research in behavioural teratology and toxicology. A final paragraph is dedicated to the bioethical aspects arisen from the use of large number of rodents subjects in behavioural testing.

Animals↗