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G Calamandrei

Publications and source records attributed to G Calamandrei.

34 records · Page 2Linked to original sources

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↗

Polypeptide growth factors in mammalian development: some issues for neurotoxicology and behavioral teratology.

Protein molecules known as Growth Factors (GFs) appear to play an important regulatory role in a number of CNS functions. In particular Nerve Growth Factor (NGF), the best characterized among about 30 GF molecules, is endowed with specific activities on cholinergic and peptidergic CNS neurons. Indexes of neurobehavioral maturation are accelerated in the mouse by neonatal NGF exposure, while a similar treatment with EGF exerts both growth-promoting and growth-inhibiting effects on somatic and behavioral development. Scopolamine hyperactivity is enhanced around weaning by NGF pretreatment. Data are discussed along with (a) NGF prevention of cholinergic system damage and (b) the molecular mechanism of endogenously-triggered CNS repair processes.

Animals↗

Epidermal growth factor has both growth-promoting and growth-inhibiting effects on physical and neurobehavioral development of neonatal mice.

The protein molecule epidermal growth factor (EGF) exerts powerful effects on mouse physical development, since repeated subcutaneous administrations of murine EGF (3.5 mg/kg, from postnatal day 2 to postnatal day 10) cause precocious eyelid opening (as early as day 8 instead of day 13 in control littermates receiving 3.5 mg/kg cytochrome c) and precocious eruption of the lower incisors (day 6 instead of day 8). By contrast, the same EGF treatment retards both the rate of body growth and the full appearance of several neurobehavioral signs of maturation, such as righting and grasping responses. Neonatal mice receiving 5 mg/kg murine nerve growth factor (NGF) under the same treatment schedule, although showing a significant retardation in body weight gain, exhibited only limited changes in neurobehavioral maturation. Specifically, the appearance of slow and swift righting, response to strong tactile stimulation, hindlimb and forelimb grasping, pole grasping, and vertical screen and screen climbing were significantly retarded by EGF and slightly advanced by NGF (the only significant NGF effect was an acceleration of swift righting maturation). Polypeptide growth factors seem to play an important role in physical and neurobehavioral development of altricial rodents, orchestrating the relative maturation of different tissutal targets on different developmental stages.

Aging↗

Odor-aversion learning and retention span in neonatal mouse pups.

One hundred and sixty-four litters of Swiss CD-1 random-bred mice were used to assess learning and retention capacities during the first postnatal week. In Experiment 1, whole 7-day litters were exposed for 65 min to commercial extracts of either mint or lemon sprinkled over wood shavings. Five minutes after the beginning of the exposure, half of the litters were injected ip with the illness-inducing agent lithium chloride (LiCl; 0.20 M, 2% of body weight); the other half was treated with saline solution (8% NaCl). On Postnatal Day 10, the animals were singly introduced in a warmed arena for a 180-s preference test, and the time spent in the mint- and lemon-scented areas of the apparatus was recorded. When compared with saline-injected pups, mice that experienced lemon-LiCl pairings showed a significant aversion for the lemon-scented area, while the mint aversion in the mint-LiCl group just missed statistical significance. Three additional control groups (unhandled on Day 7, or only LiCl- or saline-injected) did not show significant preferences for either the mint or the lemon odor. In Experiment 2, litters of 3, 5, or 7 days were similarly exposed to lemon-scented shavings for either 5 or 20 min, injected with LiCl or saline, and then exposed for an additional 60 min to the shavings. On Postnatal Day 10, tests like those of Experiment 1 showed a significant odor-aversion in animals conditioned on Day 7, but not in those conditioned on Day 3 or 5. In Experiment 3, 3- and 5-day old pups were exposed to lemon odor-LiCl or -NaCl pairings, and tested for aversion after 3 or 7 days (CS duration 5 min before injection and either 30 or 60 min after injection). Only when the conditioning-testing interval was limited to 3 days did LiCl-injected groups show a significant aversion, which did not depend on duration of CS exposure.

Animals↗

[Corrective methods of the aphaque eye (author's transl)].

While in most cases, the operation for cataract gives full satisfaction to the patient, it is nevertheless a fact that in some cases--perhaps only a few but certainly not to be neglected--the long term effects of such an operation are not well tolerated. The cause is not faculty performance of the operation, but most often unsuitable operational timing or technics or else defective or illchosen visual aids. These, therefore are the problems dealt with in this paper by the authors who made thorough study of the aphaque eye and its corrective methods.

Aphakia, Postcataract↗

Nerve growth factor influences neurobehavioral development of newborn mice.

Thirty-six male pups of the CD-1 outbred strain received from postnatal day 2 to day 10 a daily subcutaneous injection of either highly purified murine Nerve Growth Factor (NGF; 5 mg/kg), cytochrome c (5 mg/kg), or saline solution. NGF-treated pups showed a slight, but significant, reduction in body weight gain and a concomitant acceleration in the appearance of early signs of neurobehavioral maturation such as righting reflex, cliff aversion, and response to tactile stimulation of the perioral area. Other responses, including the ultrasonic vocalization pattern on day 7, were unaffected or affected to a lesser extent.

Animals↗

Neonatal exposure to bFGF exerts NGF-like effects on mouse behavioral development.

Brain cells are naturally exposed to a variety of trophic factors during development. Basic Fibroblast Growth Factor (bFGF), a protein found in the central nervous system (CNS) enhances both survival and proliferation of several CNS cell lines. Neonatal mice of the CD1 outbred strain were injected intracerebroventricularly (ICV) with bovine bFGF on postnatal days 2, 4, and 7. bFGF, dissolved in 25 microliters of saline, was given in the 1, 5, 25, and 1000 ng doses. Physical traits such as body weight gain, body length, and tail length were recorded from postnatal day (PND) 2 to PND 12. Neurobehavioral development was scored according to a modified Fox's Scale. The ultrasonic vocalization pattern (PND 8), homing performance (PND 10), open-field activity and exploration of a novel object (PND 18) were also assessed. Pups receiving 25 and 1000 ng doses of bFGF showed a slight but significant acceleration in the appearance of some early sensorimotor reflexes, such as weak and tactile stimulation, forelimb placing and grasping, and screen climbing, during the first postnatal weeks. The other responses were less affected or not affected at all. Data are compared with similar systemic exposure of neonatal mice to Nerve Growth Factor (NGF).

Animals↗

Neonatal exposure to anti-nerve growth factor antibodies affects exploratory behavior of developing mice in the hole board.

The aim of this study was to assess in developing mice whether the neutralization of endogenous NGF following ICV administration of anti-NGF antibodies (50 micrograms/2 microliters) on postnatal days 3, 6, 9, and 12 affected locomotor activity, exploratory behavior, and response to the cholinergic blocker scopolamine. In Experiments 1 and 2 activity and age-typical scopolamine effects were evaluated on PND 13 or 17 in an automated apparatus. No significant main effect of anti-NGF treatment was found at either age. On day 13 scopolamine (0.2, 1, or 2 mg/kg) decreased locomotion in both anti-NGF and control animals. In Experiment 3, locomotion and exploratory behavior were analyzed in an open field arena or in a hole board apparatus on PND 16. No significant effects of anti-NGF treatment on general motor activity and investigation of a novel object in the open field was found, though anti-NGF animals tended to be less active than controls. In the hole board anti-NGF pups showed a different pattern of head dipping behavior from controls, exploring mainly the holes located in the periphery of the apparatus.

Animals↗

Prenatal exposure to anti-HIV drugs. long-term neurobehavioral effects of lamivudine (3TC) in CD-1 mice.

The present study was aimed at investigating the long-term effects of prenatal exposure to lamivudine (3TC), an antiretroviral drug used in clinical practice alone or in combination with zidovudine (AZT) to prevent mother-to-child transmission of the HIV virus. Pregnant CD-1 mice were given per os twice daily either 3TC at different doses (125, 250, or 500 mg/kg) or vehicle solution (NaCl 0. 9%) from pregnancy day 10 to delivery. Offspring behavior was examined on postnatal day 35 in a 20-min social interaction test. At adulthood different behavioral endpoints were analyzed, including locomotor activity and exploration in an open field following administration of the muscarinic antagonist scopolamine (2 mg/kg), spatial learning in either radial arm or Morris water maze, virgin female behavior in a maternal induction test, and pain sensitivity in a hot-plate test (52 +/- 0.1 degrees C). Our findings confirm the low neurotoxicity of 3TC in comparison to AZT. However some significant behavioral alterations were found, namely (1) a decrease in immobility in the open field test, (2) an increase in the responsiveness to scopolamine shown by the 500-mg/kg 3TC mice (sniffing behavior) in the open field, and (3) a longer escape latency in the first day of the reversal phase in the Morris task (particularly marked in the 250-mg/kg treatment group). No significant changes in either pain sensitivity, social/affiliative, or maternal behavior were found, although a higher occurrence of aggressive behavior toward foster pups was noted in both 125- and 500-mg/kg 3TC females.

Animals↗

Effects of prenatal AZT on mouse neurobehavioral development and passive avoidance learning.

Recent evidence has shown that perinatal administration of zidovudine (AZT) to HIV-infected mothers reduces the risk of maternal-infant transmission of the virus. Treatment of pregnant seropositive women with AZT is becoming a common medical practice, despite the paucity of information about the potential neurotoxic/behavioral-teratogenic effects of AZT on the developing organism. The aim of the present study is to evaluate in mice the short-, medium-, and long-term effects of prenatal exposure to AZT on neurobehavioral development. Pregnant mice were given 0.2, 0.4, and 2.0 mg/ml AZT in drinking water from day 10 of gestation to delivery. Offspring's viability was severely affected in the 2.0 mg/ml AZT group. Thus, behavioral analysis was carried out in offspring of 0.2 and 0.4 mg/ml AZT-treated females only. Some limited but significant alterations were found, such as stunted body weight, delayed appearance of the pole-grasping reflex, and a slight impairment in the acquisition phase of a passive avoidance response. Moreover, sexual differences in some items of the social behavior repertoire appeared to be affected by AZT treatment.

Agonistic Behavior↗

Neurobehavioral effects of prenatal lamivudine (3TC) exposure in preweaning mice.

The present study provides a characterization of the behavioral changes induced in preweaning mice by prenatal exposure to lamivudine (3TC), an antiviral drug recently entered in the clinical practice to treat HIV patients. Pregnant CD1 mice were given per os bidaily either 3TC at different doses (125, 250, or 500 mg/kg) or vehicle solution (saline 0.9%) from pregnancy day 10 to delivery. Data on reproductive performance, such as gestation length, litter size, and offspring viability, were collected. Offspring were then examined for a series of different somatic and behavioral end points, including sensorimotor development, ontogenetic pattern of ultrasonic vocalization, passive avoidance learning, and locomotor activity. In the absence of gross changes in somatic and sensorimotor development, a slight change in ultrasound emission was found on postnatal day (PND) 3, with 125 and 500 mg/kg 3TC-treated offspring emitting a lower number of ultrasounds. Learning and retention performances of a passive-avoidance task on PND 20-21 were unaffected by 3TC treatment, while decreased habituation in an automated locomotor activity test was evident in male offspring exposed to 250 and 500 mg/kg 3TC.

Animals↗