Low nerve growth factor plasma levels in schizophrenic patients: a preliminary study.
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Adolescent↗
Biomedical subjects
E Alleva
Publications and source records attributed to E Alleva.
Long-term effects of prenatal 3'-azido-3'-deoxythymidine (AZT) exposure on intermale aggressive behaviour of mice.
RATIONALE: AZT treatment of seropositive pregnant women and their neonates has been widely used due to its effectiveness in reducing vertical transmission of HIV, but medium- and long-term effects of AZT on neurobehavioural development and adult responding are still poorly described. OBJECTIVE: The aim of the present study was to evaluate the long-term effects of prenatal AZT treatment on aggressive behaviour of adult male mice. METHODS: Pregnant CD-1 mice were given saline vehicle, 0.4, or 0.8 mg/ml AZT in their drinking water from gestation day 10 to delivery. Social-aggressive types of interaction were assessed in their male offspring following a 4-week isolation period. Two groups of subjects were used, each undergoing a different type of test: test 1 consisted of a single 20-min encounter with an isolated same-strain opponent on postnatal day (PND) 90, while in test 2 (PND 150) subjects were paired for 10 min for 5 consecutive days with a non-isolated opponent. RESULTS: Slight changes in both aggressive and defensive components of the male-specific agonistic pattern were evident only in test 1, AZT mice displaying a limited increase of aggressive behaviour compared to their controls. CONCLUSIONS: Although the long-term effects of prenatal AZT on social behaviour are limited, they may be of some relevance for paediatricians in order to plan a follow-up of infants, children and adolescents exposed in utero to antiretroviral drugs.
Aggression↗
Behavioural effects of endocrine disrupting chemicals on laboratory rodents: statistical methodologies and an application concerning developmental PCB exposure.
Appropriate behavioural tests and adequate statistical tools may help to establish the ED properties of a given compound by pointing out the alterations of selected behavioural endpoints. Frequently, laboratory collected data consist of frequencies and/or durations of specific items, and the analysis of variance (ANOVA) technique is performed to assess whether the investigated factors affect these behavioural endpoints. Moreover, when numerous aspects of behaviour are investigated simultaneously, Principal Component Analysis (PCA), a multivariate technique, may be very useful to reduce the overwhelming number of correlated original variables to a few orthogonal artificial variables (factors). Continuous Time Markov Chain (CTMC) models may be applied to analyse the time structure of a behavioural pattern when data consist of sequences of events and the time points at which they occur. Moreover, the Cox Proportional Hazard Model, a methodology originally developed for the analysis of failure time data, may help to evidence the effects of a given treatment on behavioural sequences when the assumptions of CTMC models are not fully satisfied. Analyses on data from mice of the outbred CD-1 strain (controls in a study of toxicity and exposed to PCB during development) are presented as examples to show how adequate statistical analyses and appropriate behavioural tests may reveal relevant effect of treatments otherwise not easily detected.
Animals↗
Song behavior, NGF level and NPY distribution in the brain of adult male zebra finches.
The aim of the present study was to investigate the role of nerve growth factor (NGF) and neuropeptide Y (NPY) in the higher vocal center (HVC) on singing behavior of adult male zebra finches. The results of our studies show: (a) that NGF is present in the brain of these birds and it is higher in the HVC than in the other neostriatal tissues; (b) that exogenous administration of NGF or NGF-antibody had no discernible effect on singing behavior; and (c) that NGF enhances the NPY immunoreactivity in neurons and fibers localized in HVC and other areas of the neostriatum and hippocampus whereas anti-NGF decreased NPY stained cells in the hippocampus. These studies indicate that NGF is produced in the brain of zebra finch and that it plays a role in the regulation of NPY.
Animals↗
Ultrasonic vocalizations elicit orienting and associative reactions in preweanling mice.
On postnatal days (PND) 12 and 13, 90 male Swiss CD-1 mice were tested for orientation to 3 intensities of recorded ultrasounds while climbing an inclined wire grid surface. Motor responses and vocalization to replayed ultrasounds (55-75 kHz) of 20-, 40-, and 60-dB SPL indicated an intensity dependence. In Experiment 2, 138 pups were exposed to either contingent or noncontingent pairings of recorded ultrasounds of 55-75 kHz, averaging 40 dB, and mild inescapable footshocks, or taped vocalizations or footshocks only on PND 12, 14, or 16. At PND 18, subjects were tested for passive avoidance following exposure to the taped ultrasounds only upon entry into the dark side of a black-white compartment. Results suggested only overall, nonspecific effects of pretreatment to elicit responses antagonistic to motor activity. In Experiment 3, 36 pups at PND 15 were tested for passive avoidance with the ultrasound recordings of 40- or 80-dB onset upon entry to the dark compartment; a third group had no ultrasound exposure. A significant intensity effect confirmed that the ultrasounds had prepotent properties.
Animals↗
Limited changes in handedness and morphine reactivity in CD-1 mice after pre- and postnatal ozone exposure.
Outbred CD 1 mice were either not exposed (control group) or exposed to ozone (O3) (0.3, 0.6, or 0.9 ppm), during foetal and neonatal life until the time of weaning (postnatal day (PND) 26). On PND 70 the subjects were tested for handedness using a paw preference task assessing both the animals' capability to reach a food pellet in a feeding tube and the individual preference for the use of one of the other forepaw. O3 exposure did not affect the animals' capability to learn the task but caused changes in handedness. Specifically, females exposed to the intermediate O3 concentration showed a reduced preference for the right paw than both their same-sex controls and 0.6 ppm males. On PND 100, mice underwent a hot plate test after IP treatment by either saline or morphine HCl (10 mg/kg). The results were generally in the direction of reduced drug sensitivity after exposure to the highest concentration. The evidence for this effect was more robust in the case of an organised avoidance response (wall-rearing) than in the case of a reflexive response (limb withdrawal); in the case of the former, latency data showed an effect on both males and females while frequency data showed an effect only in females. Overall, the O3 effects are suggestive of subtle CNS changes affecting mouse behavioural responses.
Animals↗
Effects of prenatal zidovudine treatment on learning and memory capacities of preweanling and young adult mice.
The present study analyzed the short and long-term effects of prenatal zidovudine (AZT) exposure on learning and memory capacities of CD-1 mice. Two tasks normally used in rodents were used, namely a passive avoidance step-through task and a Morris navigation task. AZT (0, 0.4, and 0.8 mg/ml) was administered via drinking water to pregnant CD-1 females from day 10 of gestation to delivery. Data on reproductive performance, such as gestation length, litter size, and pup mortality were collected. Avoidance learning in the offspring was tested on postnatal day (PND) 15, while spatial learning performances in the Morris water maze were obtained on PND 45. Retention of the passive avoidance response was mildly impaired in the offspring exposed to the 0.8 mg/ml AZT solution, whereas spatial learning on PND 45 was unaffected.
Animals↗
[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↗
Infection with Schistosoma mansoni in mice induces changes in nociception and exploratory behavior.
In this study, CD-1 mice were infected percutaneously with 1600 cercariae of Schistosoma mansoni and their pain sensitivity and exploratory behavior were analyzed in well-standardized tests (hot-plate, hole-board, open-field, novel object investigation and black/white box). Schistosome infection produced body weight reduction, increased analgesia, induced changes in the number of fecal pellets emitted during the hole-board and the black/white tests, induced decreased locomotion in the open-field, decreased sniffing, rearing, wall-rearing and time spent in exploratory activity. The infection also lengthened the latency time to the first transition from the white into the black compartment in the black/white box, index of enhanced anxiety. The present findings indicate that the analgesia is one of the main effects of the disease suggesting that schistosome infection induces maladaptive response in exploratory behavior and in locomotor activity of the host associated with altered motivational and attentional levels. Furthermore, though mouse behavioral changes appear to be similar to those observed in parasite/host systems where the changes are supposed to be adaptive for the parasite, in the case of Schistosoma/mouse system, the changes in host behavior resulted to be not adaptive for the parasite.
Animals↗
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↗
Exploratory and displacement behavior in transgenic mice expressing high levels of brain TNF-alpha.
Studies reported recently have shown that tumor necrosis factor-alpha (TNF-alpha) a cytokine released by macrophages and monocytes plays a key role in inflammatory processes and immune and neuro-endocrine regulation. TNF-alpha is also produced in the central nervous system (CNS). However, the role of this cytokine in the CNS is largely unknown, although evidence indicates that it is involved in various neurobehavioral manifestations. Using transgenic mice expressing high amounts of murine TNF-alpha transgene in the neurons of the CNS, we investigated the stereotyped, exploratory, and displacement activities in the hole-board and black/white box. Transgenic mice and their normal control littermates were hybrids of the CBA x C57BL/6 genetic backgrounds and were obtained by backcrossing the CBA x C57BL/6 founder female and her progeny with F1 hybrid mates. Transgenic mice did not show changes in the stereotyped behavior on the hole-board, but they displayed several alterations in the exploratory activities both in the hole-board and black/white box. Transgenic mice also exhibited an increase in grooming when exposed to a highly unfamiliar environmental stimuli in the black/white box. The study suggests that supranormal endogenous TNF-alpha in the brain affects the behavioral responses to stressful conditions.
Animals↗
Ultrasonic vocalizations by infant laboratory mice: a preliminary spectrographic characterization under different conditions.
During the first 2 to 3 weeks of life, isolated neonatal mice emit ultrasonic vocalizations, with various conditions such as hypothermia or olfactory or tactile stimulation eliciting this behavior. Although it is known that pup vocalizations stimulate prompt expression of maternal behavior, the communicative role of infant ultrasonic calls is still a matter of investigation. A fine-grained spectrographic analysis of ultrasonic calls emitted by pups exposed to different conditions was performed. Forty 8-day-old outbred CD-1 mice (Mus musculus) were isolated from their mothers and littermates and randomly exposed to one of the following conditions: (a) odor from the nest, (b) social isolation, (c) low temperature-isolation, (d) tactile stimulation, or (e) odor from a conspecific adult male. Upon consideration of the spectrogram typology and emission frequency interval, it appears that the conditions under which vocalizations are emitted influence the sound characteristics of call production.
Analysis of Variance↗
Parental recycling of nestling faeces in the common swift.
Several hypotheses have been proposed to explain why parent birds eat their nestlings' faecal sacs. Among them, the parental nutrition hypothesis suggests that faeces may provide alternative food to parent birds, while the economic disposal hypothesis proposes that eating faeces represents an economical alternative to carrying them away when birds are engaged in parental activities. In both cases the elimination of faeces could prevent contamination of the nest (nest sanitation). In the present study, we tested these hypotheses on the common swift, Apus apus. The behaviour of parents at the nest was videotaped and analysed in relation to sex, brood size and nestling age. The parents regularly swallowed faecal sacs during the first 3 weeks after the nestlings hatched, but only occasionally thereafter until they fledged. Both sexes ingested sacs at a similar rate in the first week after hatching, and ingestion rate was directly related to the number of feeding visits. Females ate significantly more sacs than males overall. The parents consumed faeces after actively searching into and around the nest cup, also during brooding spells. However, brooding decreased with increasing brood size and nestling age, while faeces consumption increased. Our results are consistent with the hypothesis that parent birds ingest their nestling faeces to recycle water and nutrients, making the 'best of a bad job' during periods of high energetic requirements. In addition, ingestion of faeces may be an alternative strategy to delay hunger and to facilitate the allocation of food to the offspring. As the nestlings grew, parents ate fewer faecal sacs. The increased begging behaviour of the young appeared to be an important factor in determining the decline of faeces consumption, as it hindered parents approaching the nest. Copyright 1998 The Association for the Study of Animal Behaviour.
Journal Article↗
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↗
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↗
A description of the ontogeny of mouse agonistic behavior.
The development of agonistic behavior was characterized in outbred Swiss CD-1 male Mus domesticus. At weaning (postnatal day [PND] 21), mice were housed either individually or as male pairs. Social encounters were carried out between dyads of initially unfamiliar same-age and same-housing subjects every 3rd day, from PND 23 to 47. The majority of both offensive and defensive elements had their onset around PND 29. Overall, their expression increased around puberty (i.e., on PND 35), which also represented the peak of an inverted U-shaped profile for the frequency of the "ambivalent" tail rattling behavior. A stability of dominance-submission relationships over development appeared, and early short latencies to display either the first crouched posture (subordinate) or the first attack (dominant) turned out to be possible predictors of adult social status. Ongoing individual housing was associated with a greater expression and an earlier onset of fighting behavior.
Aging↗
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↗
Nerve growth factor effects on the song control system of zebra finches.
The aim of this experiment was to test whether or not nerve growth factor (NGF) is involved in cholinergic processes in the avian brain, by injecting NGF into the higher vocal center (HVC) and examining its effects on adult male zebra finch song. Since NGF has been hypothesized to protect cells after injury, some birds received both NGF and ibotenic acid (IBO) lesions of HVC, while others received either NGF or IBO or neither (SHAM). Only the IBO-treated birds showed alterations in song. Although there was no evidence of cell preservation in the immunocytochemical and morphological analysis NGF appears to prevent the IBO induced impairment in song augmenting the activity of the remaining neurons and enhancing brain repair.
Animals↗