Biomedical subjects

Laura Ricceri

Publications and source records attributed to Laura Ricceri.

11 recordsLinked to original sources

PubMed2006

Developmental neurotoxicity of organophosphorous pesticides: fetal and neonatal exposure to chlorpyrifos alters sex-specific behaviors at adulthood in mice.

Developmental exposure to the organophosphorous insecticide chlorpyrifos (CPF) induces long-term effects on brain and behavior in laboratory rodents. We evaluated in adult mice the behavioral effects of either fetal and/or neonatal CPF exposure at doses not inhibiting fetal and neonatal brain cholinesterase. CPF (3 or 6 mg/kg) was given by oral treatment to pregnant females on gestational days 15-18 and offspring were treated sc (1 or 3 mg/kg) on postnatal days (PNDs) 11-14. Serum and brain acetylcholinesterase (AChE) activity was evaluated at birth and 24 h from termination of postnatal treatments. On PND 70, male mice were assessed for spontaneous motor activity in an open-field test and in a socioagonistic encounter with an unfamiliar conspecific. Virgin females underwent a maternal induction test following presentation of foster pups. Both sexes were subjected to a plus-maze test to evaluate exploration and anxiety levels. Gestational and postnatal CPF exposure (higher doses) affected motor activity in the open field and enhanced synergically agonistic behavior. Postnatal CPF exposure increased maternal responsiveness toward pups in females. Mice of both sexes exposed to postnatal CPF showed reduced anxiety response in the plus-maze, an effect greater in females. Altogether, developmental exposure to CPF at doses that do not cause brain AChE inhibition induces long-term alterations in sex-specific behavior patterns of the mouse species. Late neonatal exposure on PNDs 11-14 was the most effective in causing behavioral changes. These findings support the hypothesis that developmental CPF may represent a risk factor for increased vulnerability to neurodevelopmental disorders in humans.

Acetylcholinesterase↗

PubMed2006

A social recognition test for female mice reveals behavioral effects of developmental chlorpyrifos exposure.

CD-1 mice were exposed to the organophosphate pesticide chlorpyrifos (CPF) both prenatally (gestational days 15-18; doses 0, 3 or 6 mg/kg) and postnatally (postnatal days 11-14, doses 0, 1 or 3 mg/kg). When four-month-olds, females underwent a social recognition test in which ultrasound vocalizations (USVs) and social investigation behavior emitted by a resident female in the presence of a female partner were measured during two subsequent 3 min sessions (interval between the two sessions 45 min). Throughout the social recognition test a marked increase in USVs was found in females prenatally treated with the highest CPF dose; USV increase was also paralleled by a selective increase in frequency and not in duration of social investigation. These results confirm that developmental exposure to CPF induces long-lasting alterations in the social behavior repertoire of the mouse, thus extending our previous observations on the effects of postnatal CPF on male agonistic behavior to the female sex. They also suggest that social recognition can be easily and rapidly assessed in the female mouse making it possible to evaluate, primarily by means of USV emission, even subtle alteration of social behavioral patterns dissociated from cognitive components of individual recognition.

Agonistic Behavior↗

PubMed2006

An altered neonatal behavioral phenotype in Mecp2 mutant mice.

We examined somatic growth, somatosensory reflexes, and ultrasonic calls from postnatal day 3 to day 18 in Mecp2 mutant mice, a mouse model of Rett syndrome. Both Mecp2 null male and Mecp2 heterozygous female mice exhibited normal somatic growth, but transient delays in the development of some reflexes relative to sex-matched wild-type mice. Both Mecp2 null male and heterozygous female mice exhibited dramatic increases in ultrasonic vocalizations in response to social isolation; these differences were evident as early as postnatal day 5. These results suggest very early abnormalities in sensory reflex development and behavioral responsiveness in the Mecp2 mutants that may provide a target for early therapeutic intervention.

Animals↗

PubMed2005

Basal forebrain cholinergic lesions in 7-day-old rats alter ultrasound vocalisations and homing behaviour.

We analysed the effects of 192 IgG-saporin lesions on pnd 7 upon neonatal behavioural responses. Number of ultrasonic vocalisations (USVs) were recorded on pnds 9, 11 and 13. On pnd 13 rats underwent a homing test to measure olfactory orientation towards nest material. 192 IgG-saporin reduced the number of USVs at all ages considered while increasing number of entrancies into the nest area. These data suggest that early damage to the basal forebrain cholinergic nuclei induces significant changes in the rat behavioural repertoire as early as the second-postnatal week.

Age Factors↗

PubMed2004

Cognitive and neurological deficits induced by early and prolonged basal forebrain cholinergic hypofunction in rats.

In the present study we examined the long-term effects of neonatal lesion of basal forebrain cholinergic neurons induced by intracerebroventricular injections of the immunotoxin 192 IgG saporin. Animals were then characterised behaviourally, electrophysiologically and molecularly. Cognitive effects were evaluated in the social transmission of food preferences, a non-spatial associative memory task. Electrophysiological effects were assessed by recording of cortical electroencephalographic (EEG) patterns. In addition, we measured the levels of proteins whose abnormal expression has been associated with neurodegeneration such as amyloid precursor protein (APP), presenilin 1 and 2 (PS-1, PS-2), and cyclooxygenases (COX-1 and COX-2). In animals lesioned on postnatal day 7 and tested 6 months thereafter, memory impairment in the social transmission of food preferences was evident, as well as a significant reduction of choline acetyltransferase activity in hippocampus and neocortex. Furthermore, similar to what observed in Alzheimer-like dementia, EEG cortical patterns in lesioned rats presented changes in alpha, beta and delta activities. Levels of APP protein and mRNA were not affected by the treatment. Levels of hippocampal COX-2 protein and mRNA were significantly decreased whereas COX-1 remained unaltered. PS-1 and PS-2 transcripts were reduced in hippocampus and neocortex. These findings indicate that neonatal and permanent basal forebrain cholinergic hypofunction is sufficient to induce behavioural and neuropathological abnormalities. This animal model could represent a valid tool to evaluate the role played by abnormal cholinergic maturation in later vulnerability to neuropathological processes associated with cognitive decline and, possibly, to Alzheimer-like dementia.

Acetylcholine↗

PubMed2004

Refining learning and memory assessment in laboratory rodents. An ethological perspective.

In neuroscientific research, the importance of a multi-level approach in studying behaviour, ranging from the molecular to the behavioural level, has been increasingly recognised. In fact, behaviour represents the ultimate output of the brain, and behavioural phenotyping may provide functional information that may not be detectable using molecular, cellular, or histological evaluations. To correctly exploit the study of behaviour in the field of neuroscience, the principles and strategies of ethology must be carefully considered, so as to design appropriate experiments and accurately interpret data. In particular, ethological-type scoring, which entails both the close observation of the studied behaviour and the taking into account of its possible evolutionary history and adaptive significance, can contribute to standardising experimental protocols, so as to improve the quality of data and the welfare of the experimental animal.

Animals↗

PubMed2003

Developmental exposure to chlorpyrifos alters reactivity to environmental and social cues in adolescent mice.

Neonatal mice were treated daily on postnatal days (pnds) 1 through 4 or 11 through 14 with the organophosphate pesticide chlorpyrifos (CPF), at doses (1 or 3 mg/kg) that do not evoke systemic toxicity. Brain acetylcholinesterase (AChE) activity was evaluated within 24 h from termination of treatments. Pups treated on pnds 1-4 underwent ultrasonic vocalization tests (pnds 5, 8, and 11) and a homing test (orientation to home nest material, pnd 10). Pups in both treatment schedules were then assessed for locomotor activity (pnd 25), novelty-seeking response (pnd 35), social interactions with an unfamiliar conspecific (pnd 45), and passive avoidance learning (pnd 60). AChE activity was reduced by 25% after CPF 1-4 but not after CPF 11-14 treatment. CPF selectively affected only the G(4) (tetramer) molecular isoform of AChE. Behavioral analysis showed that early CPF treatment failed to affect neonatal behaviors. Locomotor activity on pnd 25 was increased in 11-14 CPF-treated mice at both doses, and CPF-treated animals in both treatment schedules were more active when exposed to environmental novelty in the novelty-seeking test. All CPF-treated mice displayed more agonistic responses, and such effect was more marked in male mice exposed to the low CPF dose on pnds 11-14. Passive avoidance learning was not affected by CPF. These data indicate that developmental exposure to CPF induces long-term behavioral alterations in the mouse species and support the involvement of neural systems in addition to the cholinergic system in the delayed behavioral toxicity of CPF.

Acetylcholinesterase↗

PubMed2003

Behavioral patterns under cholinergic control during development: lessons learned from the selective immunotoxin 192 IgG saporin.

The immunotoxin 192 IgG saporin (192 IgG-sap) offers a valuable tool to investigate the role of the developing basal forebrain cholinergic system in modulating behavioral functions in developing, as well as adult rats. After neonatal 192 IgG-sap lesions, rats display reduced ultrasonic vocalizations as neonates, deficits in passive avoidance learning as juveniles, and altered reactions to spatial novelty as adults. These data suggest that neonatal cholinergic depletion affects cognitive performance in juvenile and adult rats. Additionally, neonatal cholinergic depletion alters ultrasonic vocalizations, which could then alter establishing normal mother-infant relationships, and thus compound the pup's cognitive deficits. These findings underscore the importance of assessing behavior during ontogeny, as well as in adulthood.

Acetylcholine↗

PubMed2002

Early neonatal 192 IgG saporin induces learning impairments and disrupts cortical morphogenesis in rats.

We have shown previously that neonatal intraventricular injections of the selective cholinergic immunotoxin 192 IgG saporin on postnatal day 7 (pnd 7) induce marked cholinergic loss in hippocampus and neocortex and a learning impairment on pnd 15. In the present study, we analysed the behavioural, morphological and neurochemical effects of earlier intraventricular injection of the immunotoxin 192 IgG saporin (pnd 1 and 3). We hypothesised that these earlier lesions would interrupt a critical stage in neocortical maturation, and impair behavior more profoundly than the later lesions. Passive avoidance (PA) learning and locomotor activity during the PA test were assessed on pnd 15. Retention of the PA task was assessed on pnd 16. Reactivity to spatial and object novelty was assessed on pnd 180 in a spatial open field test with five objects. Choline acetyltransferase (ChAT) activity was measured in basal forebrain targets on pnd 20 and pnd 180. Neonatal administration of 192 IgG saporin resulted in a slower acquisition of the PA task in females; retention and locomotor activity were not affected. On pnd 180, reaction to spatial novelty was mildly impaired in lesioned rats of both sexes. There was a marked reduction of ChAT in the hippocampus and neocortex of lesioned rats of both sexes, at both ages. Morphological analysis of the somatosensory cortex of lesioned rats revealed alterations in cortical development with sex specific variations in total cortical thickness. These results suggest that interrupting cholinergic basal forebrain innervation of neocortex and hippocampus during the first postnatal days affects the development of cognitive behaviour, neurochemistry and cortical organisation in a sex specific manner. Furthermore, the alterations in cortical organization are more profound than those noted after a lesion later in postnatal development. These behavioural and morphological abnormalities could be considered a model for several neurodevelopmental disorders associated with mental retardation.

Animals↗

PubMed2002

NGF induces appearance of adult-like response to spatial novelty in 18-day male mice.

We investigated the effects of Nerve Growth Factor (NGF) administration on the maturation of reactivity to spatial and non-spatial novelty in developing mice. CD-1 mice of both sexes received intracerebral administration of NGF on postnatal day (pnd) 15, and their response to object displacement (spatial novelty) and object substitution (object novelty) were assessed in a spatial open-field with four objects on pnd 18 or 28. On pnd 18, NGF induced only in males precocious appearance of spatial novelty discrimination, while increasing choline acetyltransferase activity in neocortex and hippocampus of both sexes. The behavioral and neurochemical effects disappeared by pnd 28. NGF triggers adult-like responding to spatial novelty in developing mice and such effect is gender-specific.

Animals↗

PubMedDate not supplied

Animal models of mental retardation: from gene to cognitive function.

About 2-3% of all children are affected by mental retardation, and genetic conditions rank among the leading causes of mental retardation. Alterations in the information encoded by genes that regulate critical steps of brain development can disrupt the normal course of development, and have profound consequences on mental processes. Genetically modified mouse models have helped to elucidate the contribution of specific gene alterations and gene-environment interactions to the phenotype of several forms of mental retardation. Mouse models of several neurodevelopmental pathologies, such as Down and Rett syndromes and X-linked forms of mental retardation, have been developed. Because behavior is the ultimate output of brain, behavioral phenotyping of these models provides functional information that may not be detectable using molecular, cellular or histological evaluations. In particular, the study of ontogeny of behavior is recommended in mouse models of disorders having a developmental onset. Identifying the role of specific genes in neuropathologies provides a framework in which to understand key stages of human brain development, and provides a target for potential therapeutic intervention.

Animals↗