Biomedical subjects

F Cirulli

Publications and source records attributed to F Cirulli.

At least 19 recordsLinked to original sources

PubMed2006

Spatial memory deficits in middle-aged mice correlate with lower exploratory activity and a subordinate status: role of hippocampal neurotrophins.

The aim of the present work was to relate age-related individual differences in cognitive function with behavioural strategies employed in social and non-social challenges. To this purpose, the behaviour of adult (5-month-old) and middle-aged (13-month-old) CD-1 mice was scored in the social interaction, plus-maze, Morris water maze (MWM) and open-field tests. In addition, brain levels of nerve growth factor and brain-derived neurotrophic factor (BDNF) were analysed and correlated with the behaviours scored. Compared to adults, middle-aged mice showed greater anxiety in both non-social and social situations, spending less time in the open arms of the plus-maze and performing more freezing behaviour in response to aggression. Based upon their behaviour in the social interaction test, adult and middle-aged subjects were classified as dominant or subordinate and their behaviour in the open field, plus-maze and MWM tests subjected to factor analysis, taking into account age and social status. Results highlighted meaningful differences in exploratory strategies as a function of social status only in middle-aged subjects. In particular, middle-aged dominants were, overall, more explorative than same-aged subordinates, spending less time in peripheral areas and approaching more readily a novel object. Interestingly, in middle-aged mice, superior performance in the MWM task was associated with exploratory strategies exploited by dominants. At adulthood, BDNF hippocampal levels, but not specific behaviours, were positively correlated with the ability to learn a spatial task. Overall, data indicate that, in middle-aged subjects individual differences in exploratory strategies, rather than neurotrophin levels, are able to predict the degree of impairment in a spatial learning task.

Age Factors↗

PubMed2001

Role of environmental factors on brain development and nerve growth factor expression.

Numerous evidences suggest that early life events can affect the development of the nervous system, contributing in shaping interindividual differences in vulnerability to stress or psychopathology. A number of studies have shown that mothering style in rodents can produce neuroendocrine, neurochemical, and behavioral changes in the adult, although the basic mechanisms initiating this cascade of events still need to be investigated. This paper reviews research performed in our and other laboratories investigating some of the features characterizing hypothalamic--pituitary--adrenal (HPA) axis activity of rodents during early development, with a special emphasis on extrinsic, social regulatory factors, such as the mother and the siblings. In addition, a possible role for neurotrophins as mediators of the effects of external manipulations on brain development is suggested.

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

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

Paradoxical effects of D-amphetamine in infant and adolescent mice: role of gender and environmental risk factors.

The psychostimulant D-amphetamine (AMPH) increases generalised activity in adult subjects, while exerting a paradoxical "calming effect" in children with Attention-deficit Hyperactivity Disorder (AD/HD). A number of animal models have been developed to characterise the neurobiological basis of this AMPH action. In this line, the present review summarises recent work on the effects of AMPH on behavioural and physiological parameters in developing mice with a special emphasis on the role of gender and environmental risk factors. Behavioural and neuroendocrine responses to AMPH administration (0, 1, or 3 mg/kg, IP) and their relation to changes in the environment, represented by social stimuli, were studied in infant CD-1 mouse pups of both sexes at three different developmental ages (3, 8, or 18 postnatal (pnd) days). Mouse pups were assessed either in baseline condition or following 24 h maternal deprivation. AMPH exerted a paradoxical effect on CORT secretion only in maternally deprived subjects while affecting behaviour mainly in deprived female subjects, which showed a generalised shift to the left in the dose-response curve to this drug. Unwanted perseverative motor effects and possible dependence states represent side effects of AMPH administration. Further knowledge on these aspects comes from another set of studies where a shortened conditioned place preference (CPP) paradigm was employed to assess the reinforcing properties of AMPH (0, 1, 3.3, or 10 mg/kg) in developing mice on 14-17, 21-24, and 28-31 pnd. Data indicate that AMPH-CPP develops early, mice being able, already at two weeks of age, to acquire a place preference that relies on adult-like sensory, motor, and associative capacities. AMPH-CPP appears earlier in females, compared to males. A detailed analysis of acute D-amphetamine effects evidenced that the drug produces a dose-dependent increase in locomotor activity and in several responses (including stereotypes). These effects appear much larger at both post weaning stages than in preweanlings and are significantly more pronounced in females than in males. Overall these data suggest that AMPH action is dependent on the baseline level of activity and indicate a strong role of gender in the effects of this drug measured early on during development, with females showing greater sensitivity to this drug. A better understanding of AMPH action during the early ontogenetic phases, particularly its interaction with environmental factors, might extend our knowledge on the neurobiological basis of AD/HD, possibly improving the clinical efficacy of psychostimulant drugs.

Aging↗

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↗

PubMed1999

Behavioral and hormonal effects of partner familiarity in periadolescent rat pairs upon novelty exposure.

In periadolescent rats, social interactions are typically characterized by elevated levels of playful and affiliative behavior. Aim of the present study was to assess the behavioral and hormonal effects of partner familiarity upon the separation and reunion in a novel environment of established pairs of periadolescent subjects. At weaning (post-natal day, PND 21), Sprague-Dawley rats were pair housed with a non-sibling subject of the same age and sex. On PND 35, the members of each pair were separated for a 24-h period, and randomly assigned to different experimental groups: (1) sacrificed before separation; (2) sacrificed immediately after the isolation period; (3-4) placed individually in a novel cage for 30 min either in low-light or in high-light conditions; (5-6) reunited for 30 min in a novel cage either with their previous cagemate (familiar, FAM); or (7-8) with an unfamiliar rat (UNF) of the same age and sex, in either light conditions. During reunion, the occurrence of social and non-social behaviors was scored. Blood samples were collected at the end of the session from all groups and assayed for corticosterone (CORT). The separation of the two members of an established pair did not affect baseline CORT levels. Upon reunion, the presence of a conspecific exerted a significant buffering effect on the novelty-induced increase in CORT levels. Such an effect of the social companion appeared more marked in males than in females, and in FAM compared to UNF pairs. Interestingly, FAM rats also expressed a significantly higher amount of social investigation and play-soliciting behavior compared to UNF animals. Behavioral results, together with previous data, suggest that periadolescent rats housed in established pairs develop a sort of amicable relationship. The overall CORT output measured at the end of the session is also in line with this interpretation. As a whole, these findings indicate that periadolescence is a time period during rat development, during which social variables play a very important role in modulating both behavioral and physiological responses to novelty in a fashion that does not completely overlap with data on adult subjects.

Animals↗

PubMed1999

[Williams syndrome].

Williams syndrome (WS) is a rare (2-5/100,000) genetic human disorder characterised by a typical facies and mental retardation with a deficit in the visuospatial cognitive function and a relative preservation of linguistic abilities in general, and spoken language in particular. This syndrome also includes morphological anomalies, metabolic functional impairments, and likely deficits in the pattern of brain ontogenesis. The genetic basis of WS, recently identified, are presented. A cognitive profile of the WS individuals is defined and compared to Down syndrome (DS) and autism cognitive profiles. Neuroanatomical features of WS, including a reduction in brain volume, preservation of cerebellum and frontal lobes, and a reduction of posterior cortical systems, are described. The possible role of NGF (nerve growth factor)--a neurotrophin involved in the development of brain cholinergic systems and the associated behavioural functions--in the aetiology of the typical mental retardation of WS patients, is critically discussed. Future research avenues, including the identification of potential neurobiological markers in order to precociously diagnose this syndrome, are reviewed.

Biomarkers↗

PubMed1998

Behavioral effects of peripheral interleukin-1 administration in adult CD-1 mice: specific inhibition of the offensive components of intermale agonistic behavior.

Peripheral administration of interleukin-1beta (IL-1beta) in rodents reduces exploratory behavior in a novel environment while decreasing social investigation of a juvenile conspecific. In this study we wanted to test the effects of peripherally administered IL-1beta on another aspect of the mouse social repertoire, namely intraspecific fighting towards an adult male intruder. In the first experiment, sickness behavior induced by IL-1beta (1 microg/mouse) in adult CD-1 mice was assessed by direct observation of behavioral changes following placement into a novel environment. Three hours after injection, subjects were individually introduced for 20 min in a cage with clean sawdust and a number of behavioral items recorded. Blood samples were collected at the end of the testing session. Body temperature was measured right before, 1 h and 3.5 h following injection. In IL-1beta treated mice, exploration (assessed by measuring duration and frequency of Wall Rearing and Rearing behaviors) was nearly totally suppressed, while duration and frequency of behaviors such as Grooming, Bar Holding, and Digging were also markedly reduced. Administration of IL-1beta significantly elevated CORT secretion above basal levels and, as previously reported for mice, induced hypothermia (about 2 degrees C). In the second experiment, we assessed mice receiving IL-1beta (0.25; 0.5 or 1 microg/mouse or saline solution) in a social context. Three hours after injection, subjects were placed into a neutral cage for 20 min with a non-injected adult male conspecific and aggressive behavior scored. Overall, IL-1beta administration affected the social repertoire of treated mice in a dose-dependent fashion. Specifically, agonistic components of aggressive behavior were nearly totally suppressed, while the defensive elements, such as Upright Defensive posture, Upright Submissive posture, Crouching, or Flee were not affected by IL-1beta. Overall these data support the notion that sickness behavior induced by IL-1beta administration represents an organized behavioral strategy and is not an aspecific response to an illness-type of condition.

Agonistic Behavior↗

PubMed1998

Increased number of mast cells in the central nervous system of adult male mice following chronic subordination stress.

Mast cells (MCs) are amine-storing cells with heterogeneous histological, biochemical, and functional properties. They are found in connective tissue as well as in the peripheral and central nervous system (CNS) of many mammalian species. In this study we investigated whether the distribution of MCs in the CNS of adult male CD-1 mice was modified following repeated defeat stress. Experimental subjects underwent a 3-week period of fighting encounters with a highly aggressive resident. On the test day they were divided into three groups: (a) paired with the resident for 20 min; (b) placed in a cage containing the soiled bedding of the resident for 20 min; (c) placed in a cage with clean sawdust for 20 min. Results show that previous defeat stress increases the number of MCs in the thalamus, habenula, and hypothalamus of subjects exposed to a fighting opponent or to a clean cage, compared to subjects placed in a cage with the bedding of the opponent or to a group-housed, nondefeated control. These results, together with previous reports in birds and rodents, suggest that MCs have a wider role than previously expected and might be involved in the behavioral response to highly relevant psychosocial stimuli.

Aggression↗

PubMed1998

Early maternal separation increases NGF expression in the developing rat hippocampus.

Nerve Growth Factor (NGF) is a neurotrophin involved in growth and differentiation of central cholinergic neurons. In this study a maternal separation paradigm was used to test whether levels of NGF might be affected by brief manipulations of rat pups early during ontogeny. The expression of NGF mRNA was examined in 3-day-old rat pups following 45 min maternal separation using in situ hybridization. Early maternal separation in neonatal rats resulted in increased expression of NGF mRNA in the dentate gyrus and the hilus of the hippocampus. NGF protein levels measured (by means of a sensitive ELISA assay) in the whole hippocampus the day following the separation procedure did not differ in separated vs. nonseparated pups. These data indicate that brief manipulations performed early during development can affect hippocampal NGF expression.

Animals↗

PubMed1998

Behavioural characterization of interleukin-6 overexpressing or deficient mice during agonistic encounters.

Interleukin-6 (IL-6) is a cytokine released by activated immune cells which has been shown to affect brain function. In this experiment aggressive and affiliative behaviour exhibited during agonistic encounters by transgenic male mice either not expressing (IL-6 -/-) or overexpressing (NSE-hIL-6) IL-6 in the central nervous system was investigated. All subjects were isolated for 24 days before the aggressive encounter and were 52 days old at the time of testing. Subjects were placed for 5 consecutive days in a neutral cage for 15 min with an opponent of the Balb/c strain that had been previously isolated for the same amount of time. The first and the last test sessions were videotaped to evaluate the first approach and the establishment of the social role, respectively. A number of behavioural categories were later scored. When compared with wild-type controls, IL-6 -/- mice showed a higher degree of aggressive behaviour as indicated by a higher frequency of Offensive Upright Posture, an effect more pronounced on the fifth encounter. On the contrary, NSE-hIL-6 subjects showed a tendency to be more involved in affiliative-type social interactions, displaying a higher frequency and duration of behaviours such as Anogenital, Nose or Body Sniff. IL-6 -/- mice showed a clear tendency to exhibit less affiliative interactions compared with their controls while dopamine levels were found to be modified in a number of brain regions in these mice. Overall, these data suggest that IL-6 affects both aggressive and affiliative-type interactions, although the behaviour of the NSE-hIL-6 subjects was less affected than that of the IL-6 -/- group. The effects of the genetic background of the animal in screening the outcome of gene manipulations on behaviour are also discussed.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1997

Sexual segregation in infant mice: behavioural and neuroendocrine responses to d-amphetamine administration.

Individual differences arise from both genetic and epigenetic factors. The aim of this study was to test whether pups raised in distinct socio-sexual conditions would show different behavioural and neuroendocrine responses to d-amphetamine (AMPH) administration upon placement in a novel environment. This issue was addressed by testing infant CD-1 mouse pups of both sexes at three different developmental ages [3, 8, or 18 postnatal (PND) days]. These pups were raised from birth in all-male, all-female, or mixed-sex litters. AMPH effects were assessed as a function of the hypothalamic-pituitary-adrenal (HPA) axis activational state using litters that were either maternally deprived for 24 h (DEP) or normally kept with the dam (NDEP). A concomitant maternal behaviour score carried out on selected postpartum days showed that mothers taking care of all-male litters were more often involved in Active nursing than those rearing the mixed-sex ones, whereas the latter were found more often Laying still out of the nest. Basal and stress-induced corticosterone (CORT) secretion was increased in unisexually reared pups following maternal deprivation, an effect limited to PND 3. In general, neuroendocrine and behavioural responses to AMPH were found to be dissociated and were affected by sexual segregation only in conjunction with maternal deprivation. On PND 3, AMPH injection (1 or 3 mg/kg, i.p.) decreased CORT secretion in deprived unisexually reared subjects without affecting their behaviour. As a whole, behavioural changes due to unisexual rearing were limited to female subjects. On PND 8, unisexually reared females showed, upon maternal deprivation, a generalized shift to the left in the dose-response curve to AMPH for Crossing behaviour, while on PND 18 AMPH-induced stereotypies were considerably reduced in sexually segregated females, especially following maternal deprivation. Thus, maternal deprivation appeared to "sensitize" the monoaminergic system to an AMPH challenge. The individual behavioural and neuroendocrine profiles shown in response to a stressful challenge suggest that changes in social stimulation early during development might produce subtle shifts in the function of selected central monoaminergic systems.

Aging↗

PubMed1997

Prior cocaine exposure in different environments affects the behavioral responses of mouse dams.

The present study evaluated the behavioral repertoire of lactating CD-1 mouse dams when tested in an environment associated with cocaine in the premating period. Virgin females were randomly assigned for conditioning (8-day long schedule with four cocaine or saline injections administered every other day) to three experimental groups: i) Coc-Test females received one injection of cocaine (5 or 20 mg/kg IP) in the testing chamber and saline 24 h later in the home cage, ii) Coc-Home females received one injection of the same doses of cocaine in the home cage and saline 24 h later in the testing chamber, and iii) Sal-Sal control females received one saline injection in both environments. All females underwent a 25-day long wash out period during which they were mated. Their behavior was subsequently scored in the testing chamber on postpartum day 2 (drug-free state) in the presence of 3 pups from their own litter (single 15-min session). As a whole, Coc-Test dams appeared to be more involved in pup-directed activities such as pup-nosing and nest-building when compared with the Coc-Home group. In addition, non-pup directed behaviors, such as crossing, self-grooming, and rearing were higher in Coc-Test group than in other groups. The opposite was true for stereotyped gnawing activity. A measure of females' body weight gain revealed that Coc-Test 20 group was significantly higher than other groups particularly during the postpartum phase. On postpartum day 6, lactating dams were injected with the low cocaine dose (5mg/kg) and their response to a male intruder was assessed in the testing chamber (single 5-min session). A higher number of Coc-Test 5 dams showed the on nest and the upright offensive postures compared to the corresponding Coc-Home 5 group, whereas a significant higher number of Sal-Sal females showed the on top posture with respect to the Coc-Test 20 group. Oxytocin levels measured after the behavioral test showed a tendency, even if not significant, to be higher in the hypothalamus of Coc-Test dams. As a whole, the present results suggest that the alterations in maternal behavior here observed as well as the trend underlined by oxytocin values, cannot be ascribed to carry-over effects of cocaine administration in the pre-mating phase per se; rather, they seem to represent a conditioned response to the distinct environment previously associated with the drug experience.

Aggression↗

PubMed1997

Postnatal NGF administration causes adult hyperalgesia and overreactivity to social stimuli but does not reverse capsaicin induced hypoalgesia.

The present longitudinal analysis was aimed at assessing (i) the effects of developmental capsaicin (CAPS) administration on nociceptive responsivity and on the response of adult mice to social stimuli; (ii) the action of NGF on the ontogeny of the same nociceptive response and social stimuli; (iii) whether capsaicin treatment could be reversed by subsequent treatment with NGF. CD-1 mouse pups were treated with either capsaicin (50 mg/kg, s.c.) or vehicle on postnatal days (PNDs) 5 and 8. Every other day from PND 9 to PND 21 the same pups received a daily injection of NGF (0.75 mg/kg, s.c.). During both the prepuberal stage (PNDs 14, 21, and 28) and adulthood, mice were repeatedly tested in a hot-plate apparatus (52 +/- 0.1 degrees C for 1 min). At adulthood they also underwent an aggressive behaviour test. NGF-treated mice showed a shorter latency to hindlimb licking response in the hot plate compared to both controls and NGF-CAPS groups. CAPS-treated subjects showed a long-lasting hypoalgesia at both prepuberal and adult stages that was not modified by subsequent NGF treatment. Finally, NGF-treated mice were more aggressive than both controls and CAPS-NGF animals.

Aggression↗

PubMed1997

Developmental expression of the NGF receptor p140trk in the septohippocampal system of the rat: a quantitative analysis.

An RNAse protection assay was used to identify p140trk mRNA in the developing rat septohippocampal system. In both the septum and hippocampus, levels of p140trk mRNA were low at birth and increased thereafter. Levels of transcripts were found to be much higher in the septum than in the hippocampus, whereas another brain region, the hypothalamus, showed levels of expression intermediate between these two structures. Only one isoform of the p140trk receptor was found to be expressed in the rat central nervous system (CNS) during development. This isoform corresponds to the one preferentially expressed in neural tissues in the adult animal. These data show that expression of the high affinity nerve growth factor (NGF) receptor is developmentally regulated during postnatal brain development and suggest that it might mediate NGF effects on developing central cholinergic systems.

Animals↗

PubMed1996

Serum NGF levels increase during lactation and following maternal aggression in mice.

In the present study, serum levels of nerve growth factor (NGF) were assessed in virgin and in lactating female CD-1 mice. In the case of the lactating females, NGF levels were assessed both under basal conditions and 60 and 180 min following a 10 min encounter with a male or a nonlactating female mouse. Basal serum NGF levels of lactating females were higher than those of virgin females but did not increase significantly above base after an aggressive encounter with a male or a female conspecific. Female intruders were attacked in a ritualized manner. In contrast, males received numerous bites to vulnerable regions of their body. A positive correlation was found between serum NGF levels and pattern of aggression in females confronting male conspecifics. Thus, in lactating mice, serum NGF levels following an aggressive encounter relate to the specific pattern of behavior the female uses to defend the offspring.

Aggression↗