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Biomedical subjects

Enrico Alleva

Publications and source records attributed to Enrico Alleva.

At least 19 recordsLinked to original sources
PubMed2006

Early behavioural enrichment in the form of handling renders mouse pups unresponsive to anxiolytic drugs and increases NGF levels in the hippocampus.

Early life experiences, such as early handling, can influence neural development of rodents leading to changes in physiological and behavioural reactivity to stress. These effects are likely to be mediated by changes in maternal behaviour. This study analyzed the effects of different manipulations of the rearing environment on maternal behaviour and the behavioural and physiological response to mild challenges in CD-1 mouse pups early during development. Litters underwent either 15 min of neonatal handling (H) or were exposed briefly to an unfamiliar male intruder from postnatal (PND) days 2 to 14 (MI). Both groups were compared with litters which were not manipulated (NH). Compared to NH subjects, licking behaviour in the MI group was increased only on the first day of introduction of the male intruder, while the H group showed an increase in maternal behaviour on PND 10. On PND 8, pups ultrasonic vocalizations were recorded upon treatment with an anxiolytic drug (chlordiazepoxide 0, 2, or 7.5mg/kg). Results indicate that, although there were no differences among the groups when mice were injected with vehicle, handled subjects did not reduce their calling rate following drug administration, in contrast to the NH and MI groups. Following maternal separation and novelty exposure on PND 9, levels of hippocampal NGF increased significantly only in the H group. These data suggest that active pup manipulations in the form of handling favour behavioural and neural plasticity resulting in the maintenance of a high level of arousal and in increased neurotrophin levels in response to an acute manipulation. Changes in hippocampal levels of NGF might be involved in the appraisal of subtle changes in the early social environment.

Age Factors↗
PubMed2006

Deletion of the life span determinant p66Shc prevents age-dependent increases in emotionality and pain sensitivity in mice.

Oxidative stress has been implicated in the aging process. Previous studies have determined that mice with a targeted mutation of the p66(Shc) gene show reduced oxidative stress and extended life span. This study is the first behavioral characterization of mice carrying a deletion of p66(Shc). Four-, 11- and 24-months-old homozygous knockout and wild-type mice of the 129Sv/Ev strain underwent a battery of behavioral tests. Locomotion and exploratory activity were tested in the open-field test, emotional reactivity was assessed in the elevated plus-maze, while nociception was evaluated by means of the hot-plate test (50 degrees C). In addition, social behavior was assessed in a social interaction test. Our results indicate that pain sensitivity and emotional behavior in wild-type mice increase with age. Deletion of the p66 gene results in an increase in pain threshold and reduced emotionality, differences with wild-type subjects becoming more pronounced with age. Thus reduced oxidative stress throughout the life span is able to prevent some behavioral effects of aging, particularly in response to painful or emotionally arousing stimuli. These data are discussed in relation to recent views, indicating new and complex interactions between oxidative stress and emotional stress.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Communal nesting, an early social enrichment, increases the adult anxiety-like response and shapes the role of social context in modulating the emotional behavior.

Early experiences affect brain function and behavior at adulthood. Being reared in a communal nest (CN), consisting in a single nest where three mothers keep their pups together and share care-giving behavior from birth to weaning (postnatal day 25), provides a highly stimulating social environment to the developing pup. CN characterizes the natural ecological niche of many rodent species including the mouse. Here we show that, at adulthood, compared to mice reared in standard laboratory conditions (SN), CN reared mice displayed increased anxiety-like behavior, performing more thigmotaxis in the open field and spending less time in the open arms of the plus-maze. Furthermore, we showed that social context (being alone or with a familiar conspecific in the test apparatus) affects the emotional response in both the plus-maze and open field test and that the relevance of social context changes according to the early social experiences. In particular, CN mice display higher levels of anxiety-like behavior, compared to SN mice, only when alone but not in the presence of a familiar conspecific. Overall, in line with previous findings, the present study suggests that CN mice have a more elaborate social and emotional behavior compared to SN mice and thus may be more appropriate to investigate socio-emotional impairments, in particular in the case of mouse models of neurodevelopmental disorders, such as autism, or anxiety and mood disorders.

Age Factors↗
PubMed2006

Acute perinatal asphyxia at birth has long-term effects on behavioural arousal and maternal behaviour in lactating rats.

This study analysed the long-term consequences of an asphyctic event at birth on maternal behaviour and emotionality in rats. Pregnant Wistar rats were delivered by Caesarean section and the pups, still in the uterus horns, were placed into a water bath at 37 degrees C for periods of 0 (Caesarean delivery, CD) or 20 min (asphyxia, CD+20). Control subjects were born by vaginal delivery (VD). Subsequently, pups were given to surrogate mothers, weaned at 21 days, and mated at adulthood. After giving birth, differences in maternal competence and behavioural arousal were assessed observing: (i) maternal behaviour after reunion with the pups following a 3h separation, on postpartum day (PPD) 4; (ii) behaviour in an elevated plus-maze test, on postpartum day 7; and (iii) performance in a fear conditioning test, in which subjects learned to associate a conditional stimulus with an aversive unconditioned stimulus (postpartum days 7-8). Results indicate that subjects in the CD+20 group showed a deficit in maternal care, taking a longer time to retrieve the whole litter and often failing to retrieve all pups. Both CD and CD+20 groups showed higher behavioural activity in the plus-maze. In addition, when tested in the fear conditioning paradigm, the CD+20 group showed a lower latency to perform freezing behaviour in the auditory cue trial. The changes in behavioural arousal described suggest that the dopaminergic system may be a potential neurochemical target for an early hypoxic insult and indicate maternal behaviour as a useful endpoint to study the effects of early birth insult on brain function.

Acoustic Stimulation↗
PubMed2006

Early social enrichment augments adult hippocampal BDNF levels and survival of BrdU-positive cells while increasing anxiety- and "depression"-like behavior.

Early experiences affect brain function and behavior at adulthood. Being reared in a communal nest (CN), consisting of a single nest where three mothers keep their pups together and share care-giving behavior from birth to weaning (postnatal day [PND] 25), provides an highly socially stimulating environment to the developing pup. Communal nest characterizes the natural ecologic niche of many rodent species including the mouse. At adulthood, CN reared mice, compared to mice reared in standard nesting laboratory condition (SN), show an increase in BDNF protein levels and longer survival of BrdU-positive cells in the hippocampus. Open field and elevated plus maze results indicate that CN mice, although showing levels of exploratory and locomotor activity similar to those of SN mice, displayed increased anxiety-like behavior, performing more thigmotaxis in the open field and spending less time in the open arms of the plus maze. Furthermore, CN mice displayed higher levels of immobility behavior in the forced swim test. Overall, these findings show that CN, an highly stimulating early social environment, increases adult neuronal plasticity, as suggested by high BDNF levels and augmented number of newly generated cells in the hippocampus, which is associated to an increased anxiety- and "depression"-like behavior. These findings are discussed in the framework of the neurotrophin hypothesis of depression.

Age Factors↗
PubMed2006

Efficient testing strategies for evaluation of xenobiotics with neuroendocrine activity.

Maturation of neuroendocrine regulations is an extremely complex process made up of several stages, that can be permanently affected by any exogenous substances able to interfere with the hormonal signalling at various levels. The Endocrine Disrupting Chemicals (EDCs) are a heterogeneous group of xenobiotics with potential endocrine activities which have been identified as priority risk factors in toxicological research. The present review is aimed at suggesting a number of endocrine and behavioural endpoints to be used in experimental studies to: (i) characterize more thoroughly the functional effects of developmental exposure to agents known to act as endocrine disruptors and (ii) unmask possible interferences with the maturation of the hypothalamus-hypophysis-gonad/thyroid (HHG/Th) axis by different class of xenobiotics not considered as EDCs. A combined testing strategy, considering both markers of endocrine/hormonal maturation and behavioural endpoints under hormonal control in laboratory rodents, may evidence even subtle perturbations of the neuroendocrine homeostasis, that often go undetected.

Animals↗
PubMed2006

Repeated acute exposures to hypergravity during early development subtly affect CD-1 mouse neurobehavioural profile.

Exposure to altered gravitational environment, especially during critical ontogenetic phases, may induce persistent nervous system modifications and behavioural anomalies. This study evaluated the effects of hypergravity exposure on the development of the nervous system and assessed the relevance of parity in the mother's responses to altered gravitational stimuli. CD-1 mouse pups of both sexes delivered by primiparous and biparous dams were exposed to 1h of 2 G rotationally induced hypergravity from PND2 to PND9. Sensorimotor responses and somatic growth were daily measured (PND2-PND15), ultrasonic vocalisations recorded on PNDs 2, 5 and 9, and homing behaviour evaluated on PND12. In addition, spatial orientation ability was assessed in a T-maze on PND18, while mice exploratory behaviour and locomotor activity were evaluated in an open-field test (PND21). Long-term effects of hypergravity exposure on both spatial learning (Morris water-maze test) and brain levels of NGF and BDNF were also investigated at adulthood. Rotation per se induced a delay in somatic growth, sensorimotor responses and ultrasonic vocalisation profile, while hypergravity highlighted sex differences in open-field behaviour. Strategies to solve a spatial learning task, rather than learning per se, were affected by early exposure to rotation, while hypergravity selectively altered behavioural profile in the reversal phase of the test. Early exposure to rotation per se also decreased hypothalamic BDNF levels, while hypergravity reduced NGF levels in the frontal cortex. Previous maternal experience did not interact with hypergravity exposure, while differences between offspring of primiparous and biparous dams were observed in sensorimotor development and exploratory behaviour.

Animals↗
PubMed2006

Early social enrichment shapes social behavior and nerve growth factor and brain-derived neurotrophic factor levels in the adult mouse brain.

BACKGROUND: Early experiences produce persistent changes in brain and behavioral function. We investigate whether being reared in a communal nest (CN), a form of early social enrichment that characterizes the natural ecological niche of many rodent species including the mouse, has effects on adult social/aggressive behavior and nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) levels in mice. METHODS: The CN consisted of a single nest where three mothers kept their pups together and shared care-giving behavior from birth to weaning (postnatal day 25). RESULTS: Compared to standard laboratory conditions, in CN condition, mouse mothers displayed higher levels of maternal care. At adulthood, CN mice displayed higher propensity to interact socially and achieved more promptly the behavioral profile of either dominant or subordinate male. Furthermore, CN adult mice showed higher NGF levels, which were further affected by social status, and higher BDNF levels in the brain. CONCLUSIONS: Our findings indicate that CN, a highly stimulating early social environment, produces differences in social behavior later in life associated with marked changes of neurotrophin levels in selected brain areas, including hippocampus and hypothalamus.

Age Factors↗
PubMed2006

The role of voluntary exercise in enriched rearing: a behavioral analysis.

The effects of postweaning enriched rearing and home cage voluntary wheel-running exercise in adulthood were contrasted on a comprehensive battery of tests designed to assess mnemonic, attentional, emotional, and motor functions. In a 2 x 2 factorial design, female C57BL/6 mice were housed in groups in either standard or enriched cages, which were equipped with either a running or a locked wheel. They were maintained in the corresponding housing conditions for 2 months postweaning prior to, and throughout, testing. Enriched rearing was associated with anxiogenesis, hypolocomotor activity, enhanced motor skills, retarded extinction of conditioned responding, and improved water maze performance. Exercise as such enhanced motor coordination and facilitated extinction of contextual conditioning. Evidence for an interaction between enrichment and exercise was apparent in the open field test, conditioned freezing to a tone stimulus, prepulse inhibition, and acquisition of water maze reference memory. Hence, care should be taken to control for the unique contribution of wheel-running exercise when it is included as an integral component of the enrichment procedure.

Analysis of Variance↗
PubMed2005

Response to novelty, social and self-control behaviors, in rats exposed to neonatal anoxia: modulatory effects of an enriched environment.

Perinatal asphyxia is a concern for public health and may promote subtle and long-lasting neuropsychiatric disorders. In the present study, newborn Wistar rat pups underwent a repeated 20-min exposure to a 100% N2 atmosphere (or air) on postnatal days (pnd) 1, 3, 5, and 7. Half of the animals were housed during adolescence (pnd 21-35) in an enriched environment. The consequences on behavior were assessed throughout adolescence to adulthood. When scored for social performance, adolescent rats exposed to neonatal asphyxia exhibited exaggerated levels of anogenital sniffing behavior, which was normalized by enriched living. In air-exposed controls, enriched living increased the expression of affiliative and novelty-seeking behaviors, as compared to standard housing. However, this enrichment-induced behavioral plasticity was not found in rats neonatally exposed to asphyxia. At adulthood, levels of impulsivity and 5-HT2A receptors in the striatum were markedly increased in neonatal-asphyxia rats kept in standard-housing conditions. Interestingly, impulsivity and receptor density were normalized by enriched rearing during adolescence. These findings indicate profound long-lasting behavioral alterations as a consequence of repeated neonatal asphyxia in rats. Beneficial effects of stimulation by an enriched environment during the still-plastic window of adolescence are suggested in these animals.

Animals↗
PubMed2005

Prolonged prenatal exposure to low-level ozone affects aggressive behaviour as well as NGF and BDNF levels in the central nervous system of CD-1 mice.

The long-term effects on isolation-induced aggressive behaviour and central NGF and BDNF levels of gestational exposures to ozone (O(3)) were evaluated in adult CD-1 mice. Females were exposed to O(3), at the dose of 0.0, 0.3 or 0.6 ppm from 30 days prior the formation of breeding pairs until gestational day 17. Litters were fostered at birth to untreated dams and, at adulthood, male offspring underwent five successive daily encounters (15 min each) with a standard opponent of the same strain, sex, weight and age. The encounters on day 1, 3 and 5 were videotaped and agonistic and non-agonistic behavioural items finely scored. O(3)-exposed mice showed a significant increase in freezing and defensive postures, a decrease in nose-sniffing behaviour and reduced progressively the aggressive behavioural profile displayed on day 1. Reduced NGF levels in the hippocampus and increased BDNF in the striatum were also found upon O(3) exposure.

Agonistic Behavior↗
PubMed2005

Fighting in the aged male mouse increases the expression of TrkA and TrkB in the subventricular zone and in the hippocampus.

In the present study, we investigate the effect of aggressive behavior and release of nerve growth factor (NGF) on brain progenitor cells. We found that the condition of subordination enhances the level of NGF in the subventricular zone and hippocampus whereas dominance elevates brain derived neurotrophic factor (BDNF). It was also found that mRNA-TrkA is over-expressed in the subventricular zone and hippocampus of dominant and subordinate mice, whereas mRNA-TrkB is increased in the subventricular zone of both dominants and subordinates and in the hippocampus of dominant mice. Fighting was also associated with increased presence of proliferating cells in the hippocampus stained with the nuclear marker bromodeoxyuridine (BrdU). Moreover, the brain of subordinate mice displayed tyrosine hydroxylase (TH) immunoreactivity in the wall of the periventricular region of the third ventricles and a marked neuropeptide Y (NPY) presence in the hippocampus co-expressed with BrdU. These results provide additional evidence that agonistic behavior in the aged mouse alters neurotrophin levels and increases brain progenitor cells number. The functional significance of these findings is discussed.

Aggression↗
PubMed2005

Early developmental exposure to BDE 99 or Aroclor 1254 affects neurobehavioural profile: interference from the administration route.

Among the most persistent and bio-accumulative environmental pollutants are the polybrominated diphenyl ethers (PBDEs), a class of chemicals widely used as flame retardants in plastics and textile coating, and the polychlorinated biphenyls (PCBs), previously used as coolants and lubricants in electrical equipment. Monitoring programs revealed high levels of both these classes of compounds in human breast milk, raising concerns for their potential noxious effects on infants. The aim of the present study was to investigate the neurotoxic effects of 2,2',4,4',5-penta BDE (BDE 99: 18mg/kg/day) or Aroclor 1254 (A1254, a PCB mixture: 10mg/kg/day) administration, from gestational day (GD) 6 to postnatal day (PND) 21, on neurobehavioral development in the CD-1 Swiss mouse. In addition, we investigated whether the administration route affects the emergence or the magnitude of the toxic effects of BDE 99 or A1254. In particular, we compared self-administration, consisting in letting the mouse drink spontaneously the compound dissolved in oil from a syringe, with gavage, consisting in force-feeding a substance by a tube inserted in the mouth and then into the stomach, a procedure reported to be stress-inducing. Both compounds induced hyperactivity, though BDE 99 affected activity profile only during adolescence and A1254 mainly at adulthood. Levels of total circulating thyroxine were decreased by both BDE 99 and A1254 administration, though only in the latter group the decrease was statistically significant. These findings suggest a different neurotoxic action exerted by PBDEs and PCBs. An effect of the administration route, independent from the compound administered, was found on thigmotactic behavior and gavage administration affected pup body weight gain only in the A1254 group, suggesting that the stress induced by gavage procedure may either affect results per se or modulate the detrimental action of selected compounds.

Animals↗
PubMed2005

Behavioral responses of 129/Sv, C57BL/6J and DBA/2J mice to a non-predator aversive olfactory stimulus.

We examined the behavior of three inbred mouse strains (129/SvPasIco, C57BL/6J, and DBA/2J) exposed to an object soaked with the chemical component of the aversive scent (toluquinone odor) emitted by a myriapod species (Ommatoiulus sabulosus) in the presence of a predator. Subjects were exposed to the odor for three consecutive days. Behavioral responses to the toluquinone odor were characterized both by an approach phase of risk assessment and by a repeated series of approach-avoid episodes. Results indicate that toluquinone exposure reduced completely, and in a strain independent fashion, selected behaviors such as crouching, catching and eating object. Other responses were strain-dependent: the DBA (DBA/2J) strain displayed defensive burying at high levels, C57 (C57BL/6J) mice performed high levels of withdrawal while the 129/Sv (129/SvPasIco) strain showed also high levels of stretch attend posture. Compared to other tasks, this test is ethological, simple, cheap and is not affected by strain differences in appetitive-sensory responses, as shown by some strain-independent responses. These features make this task as a good complement to any exploration-anxiety test battery.

Animals↗
PubMed2005

Effects of acute hypergravity exposure and parity on maternal behavior in CD-1 mice.

We assessed the behavioral response to acute hypergravity exposure in lactating mother mice, Mus musculus of the outbred CD-1 strain. Primiparous or terziparous dams were exposed with their litters to a centrifugal force equivalent to 2G hypergravity for 1 h daily from postnatal day 2 (P2) to P9. We made detailed behavioral observations before, during and after the rotation on selected days to identify elements of the maternal behavioral repertoire vulnerable to 2G challenge. Licking and nest building were reduced during rotation while mothers sniffed and snouted their pups more. Nursing and total time in physical contact with pups were relatively stable. The effects of rotation were most pronounced on P2, dams appearing to habituate to the treatment with repeated exposure. Dam parity had a limited effect on the behavioral response to rotation, primiparous mothers tending to spend longer nursing their pups during the rotation and showing a greater tendency to lick and nest-build in post-rotation. Differences between parity groups diminished over days. Body weight was decreased in rotated primiparous dams and their pups gained less weight than stationary controls. Ultrasonic vocalization (USV) rates recorded on P2, P5 and P9 seemed to indicate delayed behavioral development in rotated pups.

Animals↗
PubMed2004

Cognitive and emotional alterations in periadolescent mice exposed to 2 g hypergravity field.

The development of the nervous system is a dynamic process where epigenetic factors play a fundamental role. Both ground-based and space research indicate that exposure to an altered gravitational environment affects rodent neurobehavioral profile and stage of development as well as duration of exposure appear to be critical for the observed effects. The behavioral profile of adolescent (28-day-old) male and female CD-1 mice upon acute 2 g exposure was characterized and emotional/anxiety responses (plus-maze), as well as spatial learning performance (Morris water-maze), were assessed respectively 24 and 48 h after hypergravity exposure. Behavioral observation indicated a transient mild sickness associated with hypergravity, with a decrease in spontaneous activity. Rotation per se induced an increase in emotional/anxious responses and a deterioration of spatial learning acquisition, while hypergravity specifically improved flexibility of spatial orientation.

Animals↗
PubMed2004

Acute global anoxia during C-section birth affects dopamine-mediated behavioural responses and reactivity to stress.

Perinatal asphyxia may induce major neurological deficits shortly after birth as well as neurological/behavioural disorders later in development. We used a rat model of global perinatal asphyxia to model acute intrauterine asphyxia around the time of birth. Caesarean section was performed in rats and their pups, still in uterus horns, were placed into a water bath at 37 degrees C for periods of 0, 10 or 20 min. Pups were then given to surrogate mothers, and examined for long-term behavioural effects of the perinatal asphyctic insult. Behavioural assessment included analysis of novelty seeking behaviour at adolescence, while spatial discrimination abilities, response to both an acute and a chronic stress, and the effects of the full D1 receptor agonist SKF 82958 on open field behaviour were assessed at adulthood. Overall, no marked abnormalities were found in the novelty seeking test, in the ability to discriminate spatial changes in the test environment and in physiological response to stress. However, adult rats subjected to severe perinatal asphyxia (20 min) showed lower activity level and lower stereotyped behaviour after the administration of SKF 82958 in an open field test. These results support the observations from human and animal studies that perinatal insult can produce long-term dysfunction of dopaminergic neurotransmission, and points to the need of more thorough examination of the potential effects of perinatal asphyxia on hypothalamic-pituitary-adrenal (HPA) axis. Altogether, the present findings suggest that the present 20 min perinatal asphyxia model might serve for the study of neurodevelopmental disorders associated with perinatal insults.

Adaptation, Psychological↗