Biomedical subjects

Francesca Cirulli

Publications and source records attributed to Francesca Cirulli.

11 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

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

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

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↗

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↗

PubMed2004

Postnatal repeated maternal deprivation produces age-dependent changes of brain-derived neurotrophic factor expression in selected rat brain regions.

BACKGROUND: Adverse life events occurring early in development may alter the correct program of brain maturation and render the organism more vulnerable to psychiatric disorders. Identification of persistent changes associated with these events is crucial for the development of novel therapeutic strategies. METHODS: We used postnatal repeated maternal deprivation (MD) from postnatal day (PND) 2-14 to investigate changes in brain-derived neurotrophic factor (BDNF) levels. RNase protection assay and enzyme linked immunosorbent assay were employed to determine the anatomic profile of neurotrophin expression at different ages following MD. RESULTS: We found that MD produces a short-term up-regulation of neurotrophin expression in hippocampus and prefrontal cortex, as measured on PND 17, whereas at adulthood, a selective reduction of BDNF expression was observed in prefrontal cortex. When adult animals were challenged with a chronic swim stress paradigm, both a reduced expression of BDNF in prefrontal cortex and a significant reduction in striatal protein levels were found only in control subjects, whereas levels in the MD group were not further decreased. CONCLUSIONS: Our data suggest that MD produces a significant reduction of BDNF expression within prefrontal cortex and striatum, which may render these structures less plastic and more vulnerable under challenging conditions.

Aging↗

PubMed2004

Intrahippocampal administration of BDNF in adult rats affects short-term behavioral plasticity in the Morris water maze and performance in the elevated plus-maze.

The present study evaluated the effects of a single intrahippocampal administration of brain-derived neurotrophic factor (BDNF) on memory retention in a water maze. Adult rats were trained in a water maze (acquisition phase, day 1). Immediately after the last training trial subjects were injected in the right hippocampus with either BDNF (24 microg) or phosphate-buffered saline (1 microl). On day 2, all subjects were tested for memory retention in a probe trial and were subsequently tested for reversal learning. While no differences emerged in the probe trial, BDNF-treated subjects showed a shorter latency and a shorter path length to reach the platform during the reversal phase. A significant difference in their "turn angle" and in their swim paths suggests that they might have used a different search strategy compared with controls. Moreover, all subjects also underwent an elevated-plus maze test. BDNF-treated-animals showed a clear tendency to spend a greater amount of time in the open arms and a significantly higher frequency of grooming behavior and of the stretched-attend posture in this maze area, but no differences in locomotion. Overall, these results indicate that administration of BDNF improves performance in a spatial memory task and has enduring effects on emotional behavior.

Animals↗

PubMed2004

Enriched environment and acceleration of visual system development.

Rearing mice from birth in an enriched environment leads to a conspicuous acceleration of visual system development appreciable at behavioral, electrophysiological and molecular level. Little is known about the possible mechanisms of action through which enriched environment affects visual system development. It has been suggested that differences in maternal behavior between enriched and non-enriched conditions could contribute to the earliest effects of enriched environment on visual development and that neurotrophins, BDNF in particular, might be involved. Here, we examined Brain Derived Neurotrophic Factor (BDNF) levels in the visual cortex during development and showed that an increase occurs in the first week of life in enriched pups compared to standard reared pups; BDNF levels at birth were equal in the two groups. This suggests a postnatal rather than a prenatal effect of environment on BDNF. A detailed analysis of maternal care behavior showed that pups raised in a condition of social and physical enrichment experienced higher levels of licking behavior and physical contact compared to standard reared pups and that enhanced levels of licking were also provided to pups in an enriched environment where no adult females other than the mother were present. Thus, different levels of maternal care in different environmental conditions could act as indirect mediator for the earliest effects of enrichment on visual system development. Some of the effects of different levels of maternal care on the offspring behavior are long lasting. We measured the visual acuity of differentially reared mice at the end of the period of visual acuity development (postnatal day 45) and at 12 months of age, using a behavioral discrimination task. We found better learning abilities and higher visual acuity in enriched compared to standard reared mice at both ages.

Aging↗

PubMed2004

Long-term effects of the periadolescent environment on exploratory activity and aggressive behaviour in mice: social versus physical enrichment.

The aims of the present study were (i) to investigate the effects of environmental enrichment during periadolescence on different behavioural and neurochemical responses in male CD-1 mice at adulthood and (ii) to describe the relative role of the physical and social components of the enrichment in producing these effects. Thirty 5-day-old mice were randomly assigned to one of the following housing conditions lasting five consecutive days: (i) individually housed in a standard cage, (ii) housed in pairs in a standard cage, (iii) individually housed in a physically enriched cage, and (iv) housed in pairs in a physically enriched cage. At adulthood, 80 days after the enrichment exposure, the explorative behaviour in an open field, as well as the behaviour in agonistic encounters, was evaluated in association with the analysis of selected central (hypothalamic levels of nerve growth factor (NGF) and brain-derived growth factor(BDNF)) and peripheral (plasma corticosterone levels) biochemical parameters. The results show that the long-term effects of the physical and the social enrichment are different and not additive. In particular, while social enrichment by itself exerted very limited effects, physical enrichment decreased the exploratory activity and altered social behaviour. Mice housed in pairs in an enriched cage showed low activity levels in the open field, and they tended to become more frequently dominant, although showing a more affiliative and less aggressive social interaction strategy. Furthermore, they presented low levels of hypothalamic NGF and high levels of brain-derived growth factor, suggesting an important effect of the combination of social and physical enrichment on neurobehavioral markers of brain plasticity and on animal ability to cope with social challenges.

Aggression↗

PubMed2003

Prolonged perinatal AZT administration and early maternal separation: effects on social and emotional behaviour of periadolescent mice.

Zidovudine (AZT) is an effective treatment in preventing perinatal transmission of HIV-1; however, a continuous re-evaluation of the risk-benefit ratio of human exposure to this drug is suggested by both clinical and animal studies. The objective of this study was to assess the medium and long-term effects of pre-postnatal AZT treatment on mouse social and emotional behaviour and the possible interactions between AZT exposure and disruptions in the mother-infant relationship. Pregnant CD-1 mice were administered per os with AZT (160 mg/kg) from pregnancy day 10, throughout delivery, to lactation day 10. In half of the litters, the offspring was separated from the mother for 3 h from postnatal days 2 (PND2) to PND14. On PND35, a 30-min social interaction test was performed and corticosterone levels were measured at the end of the session. On PND80, long-term effects of AZT on emotionality were assess by means of an elevated plus-maze. Results indicate that, on PND35, previous AZT exposure affected social behaviour of the experimental subjects, reducing aggressive interactions in males, while decreasing investigative behaviours in females. At adulthood, AZT inhibited exploratory behaviour in the plus-maze while increasing the frequency of risk-assessment postures in male mice. As for maternal deprivation, this early manipulation exerted a pro-aggressive effect in adolescent male mice, deprived subjects being overall characterised by higher activity levels and a deficit in habituation, an effect also observed in the plus-maze. A significant interaction between AZT and maternal deprivation was found for affiliative behaviours. As for corticosterone levels, no AZT effect was found, while maternal deprivation tended to reduce elevations of this hormone in response to stressful stimuli. Overall results from this study indicate that both AZT exposure and maternal deprivation induced gender-dependent changes in social and emotional behaviour both during adolescence and at adulthood.

Animals↗