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E Alleva

Publications and source records attributed to E Alleva.

At least 55 records · Page 3Linked to original sources
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

Haloperidol administration in humans lowers plasma nerve growth factor level: evidence that sedation induces opposite effects to arousal.

Studies reported in recent years have indicated that the level of nerve growth factor (NGF), in both the brain and in the bloodstream, increases following stressful events and anxiety-associated behaviour. These observations prompted us to investigate whether an anti-arousal drug would induce an opposite effect. We have reported that the administration of haloperidol (HA), a neuroleptic drug clinically used for psychiatric disorders, decreases NGF levels in the hypothalamus of adult male mice. In the present study, we showed that HA reduced the basal NGF plasma levels in 8 neuroleptic-free schizophrenic patients. These observations strengthen the hypothesis that NGF may play a functional role in stress-coping responses.

Adolescent↗
PubMed1997

[Williams syndrome: a window to the development of cognitive and neural processes].

Williams syndrome (SW) is a rare (2-5/100,000) genetic human disorder characterised by a typical facies and mental retardation with a deficit in the visuo-spatial cognitive function and a relative preservation of linguistic abilities. This syndrome also includes morphological anomalies and metabolic-functional impairments, likely deficits in the pattern of brain ontogenesis. Neuropsychological and somatic features of the SW individuals are illustrated, and the correspondent genetic bases, recently identified, are presented. The possible role of NGF (nerve growth factor), a particular neurotrophin involved in the development of brain cholinergic system and the associated behavioural functions, in the aetiology of the typical mental retardation of SW patients, is critically discussed. Prospect of researches, including the identification of potential neurobiological markers and the definition of appropriate cognitive profiles of the SW, in order to precociously diagnose this syndrome, and a more thorough investigation of factors affecting phenotypic expression of this genetically determined pathological condition, are reviewed.

Adolescent↗
PubMed1996

Developmental abnormalities and age-related neurodegeneration in a mouse model of Down syndrome.

To study the pathogenesis of central nervous system abnormalities in Down syndrome (DS), we have analyzed a new genetic model of DS, the partial trisomy 16 (Ts65Dn) mouse. Ts65Dn mice have an extra copy of the distal aspect of mouse chromosome 16, a segment homologous to human chromosome 21 that contains much of the genetic material responsible for the DS phenotype. Ts65Dn mice show developmental delay during the postnatal period as well as abnormal behaviors in both young and adult animals that may be analogous to mental retardation. Though the Ts65Dn brain is normal on gross examination, there is age-related degeneration of septohippocampal cholinergic neurons and astrocytic hypertrophy, markers of the Alzheimer disease pathology that is present in elderly DS individuals. These findings suggest that Ts65Dn mice may be used to study certain developmental and degenerative abnormalities in the DS brain.

Aging↗
PubMed1996

Neurobehavioral alterations in developing transgenic mice expressing TNF-alpha in the brain.

During development, neuronal circuitry and memory formation are associated with the synthesis and release of several biological mediators, including cytokines. Among the numerous cytokines, the role of tumor necrosis factor-alpha (TNF-alpha) in neurobehavioral development is largely unknown. Thus, the recently generated transgenic mice expressing murine TNF-alpha in the brain represent a valid animal model for investigating the role of TNF-alpha in neurobehavioral processes. Using these mice, we showed that an overexpression of murine TNF-alpha increases grooming in the novel object investigation test, decreases rearing as a reaction to novel olfactory cues, and produces a retardation of passive avoidance acquisition while enhancing the thermal response in the hot-plate test, a task regulated by both peripheral and central mechanisms. The possibility that these effects are associated with endogenous changes in concentration of the NGF, known to be modulated by TNF-alpha, is discussed.

Animals↗
PubMed1996

Schistosoma mansoni: influence of infection on mouse behavior.

Schistosoma mansoni infection in humans and animals induces abnormal neurobehavioral responses following granuloma formation. In mice, granulomas in the liver are observed 8 weeks after infection, while after 15-20 weeks, the presence of eggs and granulomas in the brain has been reported. In this study, outbred CD-1 female mice were infected with S. mansoni and examined in several behavioral tests (open field, novel object investigation, black/white box, and hot plate) 8 and 15 weeks after infection. The detected effects of schistosome infection were a reduction of body weight in 8-week infected mice, marked changes in exploration/activity, rearing, and wall-rearing in 8- and 15-week infected mice, an enhancement of sniffing and grooming in 8-week infected mice, and finally an increase in the threshold of pain response to the hot plate in 15-week infected mice. The results of the present study indicate that S. mansoni infection markedly alters exploratory behavior of mice, affecting particularly the vertical movements of the animals, and suggests that the differences in behavioral abnormalities between 8- and 15-week infected mice might be associated with modifications in the levels of nerve growth factor and cytokines induced by granulomas.

Analysis of Variance↗
PubMed1996

Behavioural disturbances in adult CD-1 mice and absence of effects on their offspring upon SO2 exposure.

Adult male and female CD-1 mice were exposed to different SO2 concentrations (0,5,12, or 30 ppm) for 24 days, from 9 days before the formation of breeding pairs to pregnancy day 12-14. This exposure was near-continuous, covering about 80% of the total time indicated. The offspring of exposed dams were cross-fostered shortly after birth to dams not previously exposed. Videorecordings of the adult subjects' activities during the first hour after the start of exposure showed marked, acute transient behavioural effects such as increase of rearing and social interactions, which were more pronounced in males than in females. Subsequent activity tests on exposure days 3, 6, and 9 showed subacute effects including a dose-dependent decrease of grooming and an increase of digging as well as changes in chamber crossing and wall-rearing which were not dose-dependent; most of these effects were more pronounced in females than in males. Food and water consumption and body weight declined in a dose-dependent fashion only after the formation of breeding pairs, when consummatory responses were enhanced in the controls. Reproductive performance as well as postnatal somatic and neurobehavioural development of the offspring (the latter assessed by an observational test battery including eight reflexes and responses) were not affected by SO2. Passive avoidance acquisition and retention at the young adult stage (60 days) and response changes produced by repeated apparatus exposure in non-reinforced animals (habituation) were similarly unaffected. Overall, the data indicate that SO2 produces transient, acute behavioural disturbances and more subtle subacute response changes in adult mice which may be due, at least partly, to a functional interference with olfactory modulation of mouse behaviour. The absence of effects on reproductive performance and neurobehavioural development of the offspring suggests that the risk to the developing organism from gestational SO2 exposure is low.

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↗
PubMed1996

NGF regulatory role in stress and coping of rodents and humans.

Nerve growth factor (NGF) is a polypeptide growth factor which exerts trophic and differentiative effects on specific peripheral and central populations of neurons. Recent data showing that various cellular types of the endocrine and immune systems are able to synthesize and release NGF have suggested that this neurotrophic factor may also play an important role in vertebrate physiologic homeostasis. Previous studies using a mouse model of aggressive behavior have shown that NGF levels increase in both plasma and the CNS following intermale agonistic encounters. More recently, we have extended this research area to include other species: in particular, humans. The data now available indicate that labour and lactation, or the occurrence of a stressful event such as the very first jump with a parachute causes in NGF plasma levels as well as changes in the distribution of NGF receptors on lymphocytes. This review aimed to outline the current understanding of NGF role in vertebrates in stress-related events.

Adaptation, Psychological↗
PubMed1996

Haloperidol treatment decreases nerve growth factor levels in the hypothalamus of adult mice.

1. In a first study different doses of haloperidol (0.6, 1.2, 2.5, 5, 10, or 20 mg/kg; intraperitoneally) were administered to adult male mice (CD-1 strain) and tested for their ability to induce catalepsy. 2. The minimal haloperidol dose inducing complete catalepsy was found to be the 10 mg/kg dose and selected for the second experiment. 3. Using an immunoenzymatic assay (ELISA) hypothalamic nerve growth factor (NGF) level was measured 20 or 180 min following haloperidol injection (10 mg/kg). 4. Haloperidol treatment decreased NGF levels in mouse hypothalamus and this effect did not differ at the two time points tested. 5. The role of hypothalamic NGF in stress-related events is discussed.

Animals↗
PubMed1996

Nerve growth factor affects passive avoidance learning and retention in developing mice.

The present studies investigate the effects of early nerve growth factor (NGF) administration on the ontogenetic profile of learning and retention capacities in mice. The learning paradigm used required the animals to withhold an escape response from a vibrating platform to avoid a punishment (step-down passive avoidance). In Experiment 1, acquisition of step-down passive avoidance was essentially the same in 11- and 15-day-old mice whereas only the latter showed significant retention after 24 h. In younger animals, data pointed to a facilitating effect of familiarization with the test environment. In Experiment 2 ICV NGF treatment on postnatal day 9 increased step-down latencies in both reinforced and nonreinforced pups on day 11. Moreover, NGF mice exposed in nonreinforcement condition on day 11 failed to acquire the avoidance response 24 h later, suggesting that the treatment anticipated the appearance of latent inhibition. Results of Experiment 3, investigating the effects of different durations of preexposure to the test apparatus on passive avoidance acquisition 24 h later, supported the specificity of NGF effects on the emergence of latent inhibition. These findings suggest that neural populations responsive to NGF trophic effect are involved in the maturation of early learning and retention capacities in rodents.

Animals↗
PubMed1996

Changes in human plasma nerve growth factor level after chronic alcohol consumption and withdrawal.

Numerous studies reported in recent years have shown that withdrawal from chronic consumption of drugs induces high levels of anxiety, both in humans and in animal models. In the present study, we demonstrated that withdrawal from chronic consumption of either ethanol or heroin causes a significant increase in plasma nerve growth factor, suggesting that the resulting anxiety condition triggers the release of this molecule. Although the functional significance of this phenomenon needs to be better defined, it is hypothesized that the increased levels of circulating nerve growth factor might be involved in homeostatic adaptive and/or reparative mechanisms.

Adult↗
PubMed1996

Appropriate end points for the characterization of behavioral changes in developmental toxicology.

The present paper is devoted to second- and higher-tier test methods for the characterization of behavioral changes produced in rodents by exposure to noxious agents during development. The paper analyzes a series of end points that are informative about specific processes and underlying regulatory mechanisms but require greater technical sophistication and larger investments than first-tier end points. This applies to ultrasonic emissions in successive postnatal periods; to mother-pup interactions, including appropriate cross-fostering controls; to social (including sexual) interaction tests from the infantile to the young adult stage; and to a variety of conditioning and learning tests using both positive and negative reinforcement.

Animals↗
PubMed1995

Developmental exposure to ozone induces subtle changes in swimming navigation of adult mice.

Following exposure to ozone (O3, 0.6 ppm) from the beginning of neonatal life until weaning, adult CD-1 mice were tested in swimming navigation, a sensitive indicator for hippocampal damage. Control mice received a sham exposure. All mice were tested at 12-13 weeks of age for their ability to find a submerged platform in a fixed location (acquisition: 18 trials, six trials per day) and for capacity to re-orient towards a new platform position (reversal: 12 trials, six trials per day). Exposure to O3 did not produce any significant impairment of swimming navigation during the acquisition phase while it slightly increased the swimming paths during the last day of the reversal phase. Mice exposed to O3 showed a slightly but significantly higher swimming speed during all the days, which was unrelated to differences in body weight and to navigational performances. Moreover, mice exposed to O3 (with the exception of one animal) had a strong tendency to make turns to the left while the controls, independent of sex, preferred clockwise turns. Data are discussed with respect to possible implications with early CNS and immune alteration leading to behavioral asymmetries at adulthood.

Animals↗
PubMed1995

Neuronal growth factors, neurotrophins and memory deficiency.

CNS and PNS ontogenesis are regulated by various proteic factors, and the best characterized of which still remains Nerve Growth Factor (NGF), a molecule exerting trophic, tropic (i.e. directing growing axons toward NGF-releasing target tissue) and differentiative effects on a number of neural and non-neural (e.g. mast-cells) cell lines. Other Growth Factors (GFs), called 'neurotrophins' (BDNF, NT-3, NT-4, NT-5) also exert similar effects on specific neural cell population. Other GFs (EGF, TGFs, IGFs, FGFs) share these growth-promoting properties with the neurotrophins. NGF appears to regulate specifically the postnatal maturation of the CNS cholinergics in altricial rodents. In adults, cholinergic neurons show retrograde transport for NGF and degeneration of cholinergic neurons after fimbria-fornix transection is prevented by NGF infusion, suggesting a role for NGF in maintaining normal cholinergic function in adulthood. However, peptidergic neurons (e.g. SP-positive cells) seem also to be influenced by perinatal NGF administration, indicating that the spectrum of NGF actions is wider than previously reported. In recent years we investigated the role of NGF in controlling behavioural maturation in the early postnatal period by comparing NGF effects with those of related and non-related neurotrophins (EGF, basic FGF, IGF-1, Transforming GF-alfa). We found that a single intracerebral injection of NGF accelerates cholinergic maturation on postnatal day (PND) 20, as shown by the enhanced reactivity to the muscarinic blocker scopolamine. Scopolamine-induced hyperactivity, normally appearing at the end of the third week, emerges already at PND 5 following NGF administration on PND 2 and 4.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Limited changes of mouse maternal care after prenatal oxazepam: dissociation from pup-related stimulus perception.

There is evidence that activity at the GABA/benzodiazepine receptor complex in specific brain areas might be enhanced during rodent motherhood. We tested the hypothesis that the manipulation of this neurochemical system by prenatal benzodiazepine exposure affects typical behavioral responses of lactating mouse dams. Outbred CD-1 mouse fetuses were administered either oxazepam (OX, 15 mg/kg) or vehicle twice a day on embryonic days 12-16 and fostered at birth to untreated dams. Female offspring were subsequently mated at the young adult stage. In a first experiment, the behavioural repertoire of the two groups of lactating females was scored (single 10-min session) from postpartum days 3 to 18. When compared with VEH dams, OX females showed a shorter duration of pup-sniffing at 7-10 days and enhanced crouching behaviour when pups had reached the age of 14-18 days. In addition, OX-treated dams used more cotton for nest construction than the controls. The two female groups were differentiated only in the presence of their offspring. In a second experiment aimed at investigating possible OX-induced changes in pup-stimulus perception, the same lactating females were challenged in sequence on postpartum day 8 with three different patterns of pup-related cues consisting of: three 8-day-old live male pups (LP), three same-age dead pups DP, or three dead pups accompanied by pre-recorded ultrasounds (DPU). In the absence of carry-over effects of prenatal dam treatment, LP stimuli elicited a higher frequency of sniffing and digging than the others, whereas the level of licking, and grooming was reduced. In conclusion, the present results indicate that the slight alteration in maternal care resulting from prenatal OX treatment can be dissociated from changes in pup-related stimulus perception.

Animals↗