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Biomedical subjects

G Calamandrei

Publications and source records attributed to G Calamandrei.

At least 19 recordsLinked to original sources

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

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

Scopolamine impairs memory recall in Octopus vulgaris.

The involvement of the central cholinergic system in predatory performance, and on the recall of individual and observational memory in Octopus vulgaris was studied by treating the animals with the muscarinic antagonist scopolamine (2 mg/kg). The absence of the effects of the injection of scopolamine on blood circulation was also checked. Scopolamine did not affect the ability of octopuses to prey on live crabs. However, it interfered significantly with memory recall. In fact, the ability to solve the jar problem was impaired within the first hour after injection (short-term effects) and was only partially recovered after 24 h (long-term). Moreover, both individual and observational learning of a visual discrimination were significantly reduced at the short- and long-term testing. These results support a role of the cholinergic system in the processes of memory recall of O. vulgaris.

Animals

Sexually dimorphic effects of anti-NGF treatment in neonatal rats.

This study investigated how chronic perinatal reduction of nerve growth factor (NGF) affected brain cholinergic markers in the two sexes. Rats received anti-NGF on postnatal days (PNDs) 2-12, and choline acetyltransferase (ChAT) activity was measured on PND 16. Anti-NGF significantly reduced cortical ChAT activity in males, but not in females; no sex-dependent effects were found in hippocampus or striatum. These data suggest sexual dimorphism in cholinergic responsiveness to NGF.

Animals

Neonatal cocaine alters behavioural responsiveness to scopolamine and cholinergic development in mice.

CD-1 mice received daily subcutaneous injections of either cocaine (20 mg/kg or 40 mg/kg) or saline solution (0.9% NaCl) from postnatal days 2 to 15. Pups were tested on days 16-17 for learning and 24-h retention of a passive avoidance task, where entering a dark compartment was punished with a mild foot shock. Locomotor activity and general behaviour in an open field arena were assessed on day 21, following administration of either the muscarinic blocker scopolamine (0.8 mg/kg) or saline solution. In addition, immunostaining for the enzyme choline acetyltransferase (ChAT) was measured in different basal forebrain areas (medial septum, striatum, and nucleus basalis) on day 30. Cocaine treatment failed to affect either learning or retention capabilities. Nonetheless, neophobic behaviour during the learning session was enhanced in control nonpunished mice exposed to the 20-mg/kg dose. In the open field test, although baseline activity levels were unaffected by cocaine exposure, the 40-mg/kg cocaine-treated pups showed decreased sensitivity to the hyperkinetic effects of scopolamine. ChAT immunocytochemistry revealed a significant reduction of the number of ChAT-immunopositive neurons in the nucleus basalis but not in the other cholinergic basal forebrain regions.

Animals

Different effects of postnatal day 1 versus 7 192 immunoglobulin G-saporin lesions on learning, exploratory behaviors, and neurochemistry in juvenile rats.

Passive avoidance learning and retention, as well as locomotor and exploratory behaviors, were assessed in rats after intraventricular 192 immunoglobulin G-saporin injections on either Postnatal Day 1 (PND1) or PND7. PND1-lesioned rats were not significantly impaired on acquisition or retention of passive avoidance. PND7-lesioned rats acquired the task slower than controls, but retention was not affected. PND7-lesioned rats were less exploratory than controls and showed reduced wall rearing. Histological analysis of PND1- and PND7-lesioned rats revealed no neuronal degeneration in hippocampus or cortex. There was a marked reduction of choline acetyltransferase (ChAT) activity in the hippocampus, cortex, and septum in the PND7-lesioned rats and a slight but significant ChAT depletion in the cortex of PND1-lesioned rats. These data suggest that the cholinergic system is critical for the learning of passive avoidance and exploratory behaviors in the developing rat.

Animals

Systemic administration of anti-NGF antibodies to neonatal mice impairs 24-h retention of an inhibitory avoidance task while increasing ChAT immunoreactivity in the medial septum.

Neonatal mice received subcutaneous injections of either antibody against murine NGF raised in goat (3 mg, injection volume 50 microliters) or preimmune serum on postnatal days 2, 4, 6, 8, 10, and 12. They were tested on postnatal days 15-16 or 20-21 for learning and 24-h retention of a passive avoidance step-through task. Immunostaining for choline acetyltransferase (ChAT) was measured in two cholinergic forebrain areas (septum and caudate-putamen) on postnatal day 16 or 21. Locomotor activity and exploratory behavior in an open-field test were also assessed on day 17 or 22, following a single administration of either scopolamine (2 mg/kg) or saline solution. While anti-NGF treatment did not affect acquisition on day 15, impairment in retention was evident on day 16. On days 20-21, no effects were found either on acquisition or on retention capabilities. Analysis of ChAT immunostaining revealed a significant increase of ChAT-immunopositive cells in the medial septal area in 16-day-old but not in 21-day-old mice. Behavior in the open-field test and age-typical response to scopolamine were not altered by anti-NGF at either of the two ages considered. These data support the view that immunological neutralization of endogenous NGF specifically affects the maturation of retention capabilities in altricial rodents, and confirm the involvement of forebrain cholinergic mechanisms in early memory processes.

Aging

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

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

Impairment of passive avoidance learning following repeated administrations of antibodies against nerve growth factor in neonatal mice.

CD-1 Swiss mice were used to study the effects of repeated intracerebroventricular (i.c.v.) injections, on postnatal days (PND) 3, 6, 9, of rabbit antiserum (50 micrograms) raised against murine nerve growth factor (NGF) both on locomotor activity in an open field test (PND 10) and on a passive avoidance learning test (PND 11 and 12). While no difference was evident in locomotor activity levels between anti-NGF and control pups, an impairment of anti-NGF pups was detectable in the passive avoidance performance. Removal of endogenous NGF seems to produce a detrimental effect on a behavioural performance which is known to be under central cholinergic control, confirming previous reports on the role of NGF in early neurobehavioural responding in altricial rodents.

Acetylcholine

Age-dependent effects of NGF and scopolamine on suckling behavior of neonatal mice.

Nerve growth factor (NGF) influences the neurochemical differentiation of central cholinergic neurons of developing rodents. In this study, NGF was given intracerebrally to mice on different postnatal days (days 5 and 7, or days 8 and 10). Pups were tested for suckling behavior 24 h after the second NGF injection, following systemic administration of either the muscarinic cholinergic antagonist scopolamine or saline solution. Scopolamine significantly impaired nipple attachment on day 11 but not on day 8, and decreased locomotor activity in 11-day pups. NGF given on days 5 and 7 increased paddling and treading on day 8, and this effect was more pronounced in scopolamine injected pups. Pretreatment with NGF on days 8 and 10 decreased activity levels in 11-day pups. The differences in the effects of scopolamine at successive ages suggest that distinct portions of the cholinergic system mature at different rates and that sensitivity to NGF is age dependent. NGF appears to influence functional maturation of that portion of the cholinergic system involved in the regulation of locomotor activity.

Aging

IGF-I and IGF-I24-41 but not IGF-I57-70 affect somatic and neurobehavioral development of newborn male mice.

Insulin-like growth factor (IGF-I) is a trophic factor for both neurons and glial cells. Its presence in developing and adult nervous system suggests an important role for this peptide in the development of neural circuitries. Neonatal male mice of the CD-1 outbred strain were injected intracerebroventricularly with either recombinant IGF-I, synthetic IGF-I fragment 24-41 or IGF-I fragment 57-70 on postnatal days (PND) 2, 4, and 7. Physical traits such as body weight gain, body length, and tail length were recorded daily from PND2 to PND13. Sensorimotor development was scored according to a modified Fox's scale. The ultrasonic vocalization pattern on PND8 and homing performance on PND10 were also recorded. Measures for body weight gain and tail length of the pups were significantly increased following treatment with the whole IGF-I peptide. However, neither IGF-I nor the smaller fragments affected mice sensorimotor development. IGF-I and IGF-I24-41 but not IGF-I57-70 increased the rate of ultrasonic calls of the pups measured on PND8. These data provide evidence that IGF-I regulates somatic growth and behavioral development when administered in newborn mice and that different portions of the peptide can exert different effects.

Animals

Prenatal oxazepam affects passive avoidance performance of preweaning mice.

CD-1 outbred mice were exposed to oxazepam on fetal days 12-16 by maternal administration (per os of 15 mg/kg twice daily at 8 a.m. and 8 p.m.) and fostered at birth to untreated dams, while control mice received vehicle solution. Mice were then tested on postnatal day 14 and 15 in a passive avoidance apparatus for their ability to withhold a step-down response from a vibrating platform. The step-down response was punished with a mild footshock. Each animal was subjected to a maximum of 15 trials. Mice prenatally treated with oxazepam showed an impairment in the acquisition of the task as indicated by shorter latencies to step-down throughout the 15 trials in both sessions (days 14 and 15). As control nonreinforced animals prenatally treated with oxazepam did not show a similar alteration in latency to step-down, these data suggest that prenatal exposure to oxazepam influences behavioral performance of preweaning mice in an aversively motivated task.

Animals

Differential expression of Fos protein in the brain of female mice dependent on pup sensory cues and maternal experience.

Immunoreactivity for Fos protein following 30 min of sensory and behavioral experience with foster pups was measured in different brain areas of nulliparous female Balb/c mice who were intact, ovariectomized, or selectively depleted of olfactory bulb noradrenaline. Fos expression was also investigated in intact nulliparous female mice undergoing distal exposure to pup sensory cues. Behavioral interaction with pups increased Fos immunoreactivity in the olfactory areas (anterior olfactory nucleus, piriform cortex, corticomedial amygdala, and entorhinal cortex) as well as in the medial preoptic area, and this occurred regardless of whether females were intact or ovariectomized. Noradrenaline depletion of the olfactory bulb prevented Fos induction in primary olfactory areas, but not in the medial preoptic area, whereas distal exposure to pup cues enhanced Fos expression in the olfactory areas but not in the medial preoptic area.

Amygdala

Growth factors in behavioral teratology.

Polypeptide Growth Factors are protein molecules which regulate cell proliferation and/or differentiation. A number of different Growth Factors (GFs) have been identified and characterized in recent years, and they have been shown to control several physiological processes, such as growth, repair, differentiation, and development of specific cell populations. In particular Nerve Growth Factor, the best characterized among the about 30 GF molecules, is endowed with specific activities on cholinergic and peptidergic CNS neurons. Several GFs originally named according to their biological activity (Epidermal Growth Factor, EGF; Fibroblast Growth Factor: FGF; Transforming Growth Factor: TGF; Insulin-like Growth Factor: IGF) have been recently found in the central nervous system. The effects of in vivo GF administration on the ontogenesis of altricial rodents are reported. Indexes of neurobehavioral maturation are accelerated upon neonatal NGF and bFGF exposure, while a similar treatment with EGF exerts both growth-promoting and growth-inhibiting effects on mouse somatic and behavioral development. Administration of IGF appears to affect ultrasonic vocalization in mouse pups. Moreover, NGF given intracerebroventricularly to newborn mice anticipates both the appearance of the scopolamine-induced hyperactivity and the maturation of behaviours under cholinergic control. The present findings are in agreement with a model where different GFs can "switch on" developmental events leading sometimes to dramatic changes in the normal ontogenetic pattern.

Age Factors

Olfactory recognition of infants in laboratory mice: role of noradrenergic mechanisms.

Noradrenaline depletion of the olfactory bulbs induces cannibalism at parturition in primiparous mice, without producing anosmia or impairment of maternal behaviour. Similar lesions made in multiparous experienced females do not result in cannibalism. The present studies investigated 1) whether a 30-min exposure to pups or to distal cues from pups given to virgin females before noradrenaline depletion of the olfactory bulbs overcame the impairment in recognition at first parturition, and 2) whether noradrenaline-depleted females allowed to care for their pups for the 24 h following parturition showed a failure in recognition on a second parturition. Experiment 1 showed that exposure to distal cues from pups enabled the females to successfully recognize pups at parturition in comparison to naive females. However, neither the exposure to pup cues nor the fully interactive experience with pups overcame the disruptive effect on recognition at birth of the noradrenaline depletion. In Experiment 2, we found that olfactory recognition was impaired in noradrenaline-depleted females on second parturition, in spite of the mothering experience with their own pups.

Animals

NGF and cholinergic control of behavior: anticipation and enhancement of scopolamine effects in neonatal mice.

Male mouse pups of the Swiss-CD1 strain received on postnatal days 2 and 4 either an intracerebroventricular (i.c.v.) administration of 30 micrograms murine nerve growth factor (NGF) or cytochrome c. Pups were then tested for suckling behavior on their anesthetized multiparous dam on day 5, following intraperitoneal (i.p.) administration of either the muscarinic cholinergic antagonist scopolamine (2 mg/kg) or saline solution (0.9%). Scopolamine produced a significant increase in latency time to suckle, while reducing the time pups spent attached to the nipple. NGF exposure enhanced scopolamine effects on latency to suckle as well as on time spent attached to the nipple. More striking, NGF pups showed a marked hyperactivity after scopolamine, an effect which normally appears only around weaning time. These results support the hypothesis that NGF plays a crucial role in the functional maturation of central cholinergic mechanisms involved in the control of behavior.

Animals

On the functional role of polypeptide growth factors in rodent neurobehavioral development.

A number of polypeptide growth factor molecules have been discovered and characterized in the recent years. Most of them appear to play important roles in the ontogeny of both vertebrates and invertebrates, and some growth factors are specifically involved in brain development of altricial mammals such as rats and mice. In particular, Nerve Growth Factor (NGF) seems to be involved in degenerative processes of the aged CNS and to control brain development, particularly cholinergic systems. Data concerning NGF effects on neurobehavioral development of neonatal mice are reported, and compared with the specific alterations caused by neonatal Epidermal Growth Factor (EGF) exposure on a number of physical and behavioral scores. While NGF mainly anticipated behavioral development, EGF exerted both growth-promoting and growth-inhibiting effects.

Aging