Biomedical subjects

G Calamandrei

Publications and source records attributed to G Calamandrei.

At least 19 recordsLinked to original sources

PubMed2006

The cannabinoid receptor agonist WIN 55,212-2 attenuates the effects induced by quinolinic acid in the rat striatum.

The ability of CB(1) receptors to regulate the release of glutamate in the striatum, together with the finding that, in experimental models of Huntington disease (HD), both endocannabinoid levels and CB(1) receptor densities are reduced, has prompted the investigation on the neuroprotective role of the cannabinoids in HD. Quinolinic acid (QA) is an excitotoxin that, when injected in the rat striatum reproduces many features of HD and that acts by stimulating glutamate outflow. The aim of the present study was to test the ability of the cannabinoid receptor agonist WIN 55,212-2 to prevent the effects induced by QA in the rat striatum. In microdialysis experiments, probe perfusion with WIN 55,212-2 significantly and dose-dependently prevented the increase in extracellular glutamate induced by QA. In electrophysiological recordings in corticostriatal slices, the application of WIN 55,212-2 prevented QA-induced reduction of the field potential amplitude. Both effects of WIN 55,212-2 were prevented by the CB(1) receptor antagonist AM 251. In in vivo experiments, intrastriatal WIN 55,212-2 significantly attenuated the striatal damage induced by QA, although no significant effects were observed on a behavioural ground. These data demonstrate that the stimulation of CB(1) receptors might lead to neuroprotective effects against excitotoxic striatal toxicity.

Animals↗

PubMed2003

Neonatal cholinergic lesions and development of exploration upon administration of the GABAa receptor agonist muscimol in preweaning rats.

Neonatal rats were administered 192 IgG-saporin (192 IgG-Sap), a selective cholinergic immunotoxin, on postnatal day (PND) 7. Behavioural responsiveness to muscimol, a GABAa receptor agonist, was then assessed using locomotor activity and object exploration tests on PND 18. In Experiment 1, 192 IgG-Sap-lesioned and control rats were injected with the GABAa agonist, muscimol, on PND 18 and tested in a standard open field test. Muscimol reduced rearing responses in both control and 192 IgG-Sap-lesioned animals whereas reduced wall-rearing responses occurred in control animals only. 192 IgG-Sap also reduced rearing and wall-rearing responses. In Experiment 2, muscimol effects were evaluated on PND 18 in a spatial open field test in which object exploration in addition to locomotion and rearing responses was assessed. Neonatal cholinergic lesion per se increased locomotion during object exploration while decreasing time spent exploring objects. Depressant effects of muscimol on object exploration were also evident. As a whole, these data provide evidence for (i) basal forebrain (BF) cholinergic control on locomotor activity and object exploration and (ii) GABAa-mediated regulation of selective behavioural patterns associated with locomotion and exploration in weaning rats. Neonatal cholinergic lesions, however, do not appear to alter reactivity to GABAergic agonists in juvenile rats.

Animals↗

PubMed2001

Prenatal exposure to anti-HIV drugs: neurobehavioral effects of zidovudine (AZT) + lamivudine (3TC) treatment in mice.

BACKGROUND: The new antiretroviral treatments that combine the zidovudine (AZT) regimen with lamivudine (3TC) appear as a cost-effective alternative to the current AZT monotherapy to prevent mother-to-fetus transmission of the HIV-1 virus. Recent evidence in uninfected children raised concern about the long-term effects of perinatal exposure to AZT and 3TC, especially when used in combination. Animal studies indicated behavioral changes in offspring exposed perinatally to both AZT and 3TC, whereas no animal data are available on the effects of the perinatal exposure to the AZT + 3TC combination on neurodevelopment. METHODS: Pregnant CD-1 mice received p.o. AZT + 3TC (160 and 500 mg/kg, respectively) or vehicle solution (NaCl 0.9%) twice daily from gestational day 10 to delivery. Maternal reproductive endpoints such as pregnancy length, abortion, litter size, sex ratio, and offspring viability were assessed. Pups were scored for different somatic and behavioral endpoints, including sensorimotor development, homing performance on postnatal day (PND) 10, passive-avoidance testing (PND 22-23), locomotor activity (PND 23), and social interaction (PND 35). RESULTS: While no effects were observed on maternal reproductive endpoints, treated pups showed a long-lasting reduction of body weight and a slightly delayed maturation of placing and grasping reflexes and pole grasping. No effects on passive-avoidance or locomotor activity were found. AZT + 3TC-treated mice showed selective alterations in the social interaction test; the treated female offspring also displayed a significant reduction of affiliative interactions. CONCLUSIONS: The combination of AZT and 3TC (1) induced small, but more marked, effects on somatic and sensorimotor development than either of these drugs administered separately; and (2) affected juvenile social behavior.

Animals↗

PubMed2001

Delayed developmental effects following prenatal exposure to drugs.

Increasing evidence points to the possible risks of delayed effects upon prenatal exposure to chemicals; the evaluation of such effects may pose serious problems to clinicians, epidemiologists and toxicologists. In fact, several systems (e.g., nervous, excretory) show important developmental processes well after the organogenetic period, up to the postnatal phase; accordingly, these are also expected to be sensitive targets of developmental toxicants, resulting in impairment of the function and/or functional reserve. This review describes the effects of several groups of drugs on the functional maturation and histogenesis of the kidney (e.g., aminoglycosides, angiotensin-converting enzyme inhibitors, indomethacin) and brain (e.g., anticonvulsivants, antiretroviral compounds, benzodiazepines) upon exposure in utero of humans and laboratory animals. The available data stress the importance for risk assessment of an adequate knowledge of both developmental biology and mechanisms of toxicity. The design of developmental toxicity studies should allow an evaluation of targets most relevant for a given drug (or group of drugs); moreover, the analysis of functional development should receive the due attention within the safety assessment of chemicals.

Animals↗

PubMed2001

[Animal models of hypoxic-ischemic encephalopathy].

This review presents the animal models more widely used to study neurological and neuropathological outcomes of perinatal asphyxia. Methods used to induce hypoxia/ischemia in fetal and newborn non-human primates, lambs, piglets and rodents are concisely described, reporting the more relevant neuropathological and behavioural findings. In line with human observational data, experimental studies indicate that motor behaviour and attentional/cognitive abilities are among those behavioural regulations more significantly affected by perinatal asphyxia.

Animals↗

PubMed2001

Developmental profile of serum nerve growth factor levels in Rett complex.

Rett syndrome (RS) is a progressive neurodevelopmental disorder predominant in females, characterised by mental deficiency, stereotyped hand-washing and apraxia. Notwithstanding the recent identification of the MECP2 gene likely involved in the pathogenesis of SR, the neurobiological bases of this syndrome are still largely unknown. Converging evidence shows that the brain levels of nerve growth factor (NGF), a neurotrophin regulating the development and functioning of central cholinergic neurons, are decreased in RS girls. In this study, the serum levels of NGF were measured in classic RS, in the preserved speech variant (PSV) and in normal controls. Overall analysis failed to evidence significant differences among the three groups. However, whereas NGF levels increased significantly with age in controls, the opposite profile was observed in classic RS, with a progressive age-dependent decrease of NGF. In PSV subjects NGF levels remained constant with age. These findings strengthen the hypothesis of NGF involvement in the pathogenesis of RS.

Adolescent↗

PubMed2000

Ontogeny of spatial discrimination in mice: a longitudinal analysis in the modified open-field with objects.

The present longitudinal study investigated the emergence of spatial discrimination and reaction to novelty in CD-1 mice, using a modified open-field test with four objects, a test in which responses to both spatial rearrangement of familiar objects and object novelty are assessed. Male and female mice were tested on postnatal days (pnd) 18, 28, 46 and 90. Locomotor activity was highest on pnd 90, whereas time spent on objects before rearrangement was highest on pnd 46. Eighteen-day old mice were unable to detect both object rearrangement and object novelty, suggesting immaturity in processing spatial information. On days 28 and 46 mice showed a clear response to object novelty, actively exploring the unfamiliar object placed in the arena, while at these ages object displacement elicited a generalized increase of exploration, not directed towards the displaced objects. A clear and selective response to object displacement emerged only at adulthood (day 90).

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

Effects of prenatal AZT+3TC treatment on open field behavior and responsiveness to scopolamine in adult mice.

Treatment of pregnant seropositive women and their neonates with the nucleoside analogs (reverse transcriptase inhibitors) zidovudine (AZT), lamivudine (3TC) and their combination has become a standard of care in industrialized countries to prevent transmission of the HIV-1 virus. Animal studies indicated limited but significant behavioral changes in AZT or 3TC-prenatally exposed offspring, whereas data on the potential neurobehavioral outcomes of AZT+3TC combination are still lacking. The aim of the present study was to assess in mice prenatally exposed to AZT+3TC the functional state of cholinergic muscarinic neuroregulation at adulthood. Pregnant CD-1 mice received per orem twice daily AZT+3TC (160 and 500 mg/kg, respectively) or vehicle solution (NaCl 0.9%) from gestational day (GD) 10 to delivery (GD 19). Locomotor activity, exploratory behavior and responsiveness to the muscarinic cholinergic blocker scopolamine (2 mg/kg) were analyzed at adulthood (PND 70) in offspring of both sexes in an open field test. Results indicated that prenatal AZT+3TC exposure does not influence responsiveness to the muscarinic cholinergic antagonist as measured by analysis of the drug's effects on locomotor and exploratory activity and different behavioral items. However, AZT+3TC-treated mice displayed higher frequency of rearing, and lower frequency and duration of self-grooming behavior, consistent with an effect on dopaminergic neurotransmission. However, this would need confirmatory experiments.

Animals↗

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

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↗

PubMed1999

Neonatal 192 IgG-saporin lesions of basal forebrain cholinergic neurons selectively impair response to spatial novelty in adult rats.

The role of the developing cholinergic basal forebrain system on cognitive behaviors was examined in 7 day-old rats by giving lesions with intraventricular injections of 192 IgG-saporin or saline. Rats were subjected to passive avoidance on postnatal days (PND) 22-23, water maze testing on PND 50-60, and a open-field test (in which reactions to spatial and object novelty were measured) on PND 54. Behavioral effects of the lesions were evident only in the open-field test with 5 objects. Unlike controls, the lesioned rats did not detect a spatial change after a displacement of 2 of the 5 objects. Control and lesioned rats, however, showed comparable novelty responses to an unfamiliar object. Lesion effectiveness was confirmed by 75% and 84% decreases in choline acetyltransferase activity in cortex and hippocampus. These results suggest that the developing cholinergic system may be involved in spatial information processing or attention to spatial modifications.

Animals↗

PubMed1999

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↗

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

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↗

PubMed1997

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↗

PubMed1997

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↗

PubMed1997

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↗