Biomedical subjects

Elena Choleris

Publications and source records attributed to Elena Choleris.

12 recordsLinked to original sources

PubMed2006

Decreased cADPR and increased NAD+ in the Cd38-/- mouse.

CD38 is a type II glycoprotein that catalyzes the formation of cyclic ADP-ribose (cADPR), an intracellular calcium signalling molecule, from nicotinamide adenine dinucleotide (NAD(+)). Using a modified version of the fluorimetric cycling assay for cADPR which reduces between-subject variability, we report significant decreases in brain and lung cADPR, which although similar to previously published values, showed much less individual variation. The reduced variation within each group suggests that the range of cADPR is narrower than previously thought, and that the regulatory mechanisms controlling these levels are more finely tuned. We also report significant increases in brain, lung, and kidney NAD(+) in the Cd38(-/-) mouse, and provide the first experimental demonstration of the proximate relationship between CD38 and NAD(+).

ADP-ribosyl Cyclase 1↗

PubMed2006

Inadvertent social information and the avoidance of parasitized male mice: a role for oxytocin.

Social information can be acquired either directly or indirectly from cues inadvertently produced by individuals with similar interests and requirements ("inadvertent social information," ISI). These inadvertent cues provide "public information" that other individuals can use to guide their behavior. We show here that female mice use olfactory ISI to determine their choice of, and responses to, males and that the use of this ISI involves the gene for oxytocin (OT). Female mice (OT wild type and CF-1 strain) displayed a significant interest in, and choice of, the odors of uninfected males of varying sexual status that were associated with the odors of an another estrous female. This recognition of, and choices for, specific, individual male odors was evident 24 h later. Female mice also distinguished between males subclinically infected with the gastrointestinal nematode parasite, Heligimosomoides polygyrus, and nonparasitized males, displaying aversive responses (analgesia, increased corticosterone) to, and avoidance of, the odors of infected males. The presence of the odors of another estrous female with that of the infected male, which are indicative of potential mate interests, attenuated these aversive responses and resulted in a choice for the odors of infected male. OT gene-deficient (knockout) females were impaired in their use of this ISI to modulate their responses to either uninfected males of differing sexual states or infected males. These findings suggest that OT genes are necessary for the processing of inadvertent social information and likely the integration of both direct and indirect social information.

Animals↗

PubMed2006

Use of salient and non-salient visuospatial cues by rats in the Morris Water Maze.

In the Morris Water Maze (MWM), an animal learns the location of a hidden platform relative to distal visual cues in a process known as spatial learning. The visual cues used in MWM experiments are invariably salient in nature, and non-salient cues, such as subtle environmental variations, have not traditionally been considered to play a significant role. However, the role of non-salient cues in spatial navigation has not been adequately investigated experimentally. The objective of this experiment was therefore to determine the relative contribution of salient and non-salient visual cues to spatial navigation in the MWM. Animals were presented with an environment containing both types of visual cues, and were tested in three successive phases of water maze testing, each with a new platform location. Probe tests were used to assess spatial accuracy, and several cue variation trials were run in which both salient and non-salient visual cues were manipulated. It was observed that removal of the salient visual cues did not cause a significant deterioration in performance unless accompanied by disruption of the non-salient visual cues, and that spatial navigation was unimpaired when only the salient visual cues were removed from view. This suggests that during place learning in Long-Evans rats, non-salient visual cues may play a dominant role, at least when salient cue presentation is limited to four cues.

Analysis of Variance↗

PubMed2005

Recognition and avoidance of the odors of parasitized conspecifics and predators: differential genomic correlates.

In many species of animals chemical stimuli are an important source of information about the threats and dangers present in the social and non-social world. Olfactory cues play a fundamental role in modulating social recognition and interactions in a wide variety of mammals. Rodents, in particular, utilize chemical signals, to recognize and avoid conspecifics infected with parasites and other pathogens. Animals also respond to, and utilize, predator odor related information to assess and minimize their risk of predation. In this review, we briefly focus on the relations between odors, parasite recognition and avoidance and consider some of the associated hormonal, neural and genomic mechanisms. We describe how both male and female rodents distinguish between infected and uninfected males on the basis of odors, displaying aversive response to, and avoidance of, the urine odors of infected individuals. We further describe how the recognition and avoidance of the odors of infected individuals involves genes for the neuropeptide, oxytocin, (OT), and estrogenic mechanisms. We show that mice with deletions of the oxytocin gene (OT knockout mice (OTKO)) and mice whose genes for estrogen receptor (ER)-alpha or ER-beta [ER knockout mice (ERKO), alphaERKO and betaERKO] have been disrupted are specifically impaired in their recognition, avoidance, and memory of the odors of infected individuals. We contrast this with the recognition and display of aversive responses to predator (cat) odor that are insensitive to these genetic manipulations. These findings reveal some of the mechanisms associated with the olfactory mediated recognition of parasitized individuals and predators.

Animals↗

PubMed2005

Genes, odours and the recognition of parasitized individuals by rodents.

Social recognition, whereby animals identify and recognize other individual conspecifics, is a crucial prerequisite for a wide range of social behaviours. There are relationships among social odours (chemical signals), parasite recognition and avoidance that are associated with hormonal, neural and genomic mechanisms in rodents. Rodents use social odours to: (i) distinguish between infected and uninfected individuals; (ii) recognize specific infected individuals; and (iii) avoid and display aversive responses to infected individuals. There are genomic correlates of this parasite recognition and avoidance in which genes expressing the neuropeptide oxytocin have roles. In this article, we provide a framework ("micronet") by which the genetic, hormonal and neural interactions associated with social behaviours and recognition and avoidance of parasitized individuals can be explored.

Animals↗

PubMed2005

Genes for sex hormone receptors controlling mouse aggression.

The stereotypies of mouse social behaviours have encouraged their systematic analysis in this genetically tractable animal. Following experiments with genes for nuclear receptors and other neuroendocrine genes, we can state seven 'lessons' of gene/behaviour causal relations bearing on sociosexual and aggressive behaviours. The effect of a given gene on a given behaviour depends upon: (1) exactly when and where that gene is expressed in the brain; (2) the gender of the animal in which it is expressed; (3) the age of the animal; (4) the nature of the opponent; and (5) the form of aggression (e.g. testosterone-facilitated aggression vs. maternal aggression). (6) Better social recognition is correlated with lower levels of aggression. We have gathered evidence for a four-gene micronet involving oestrogen receptors alpha and beta, oxytocin, and the oxytocin receptor as expressed in the hypothalamus and amygdala. (7) Some genetic influences on aggression derive from their effects on fundamental, generalized arousal of the mammalian brain, which underlies the expression of any emotional behaviour.

Aggression↗

PubMed2004

Olfactory-mediated parasite recognition and avoidance: linking genes to behavior.

A major cost of social behavior is the increased risk of exposure to parasites and infection. Animals utilize social information, including chemical signals, to recognize and avoid conspecifics infected with either endoparasites or ectoparasites. Here, we briefly discuss the relations among odors, parasite recognition, and avoidance, and consider some of the associated hormonal, neural, and genomic mechanisms. In rodents, odor cues mediate sexual and competitive interactions and are of major importance in individual recognition and mate detection and choice. Female mice distinguish between infected and uninfected males by urinary odors, displaying aversive response to, and avoidance of, the odors of infected individuals. This reduces both the likelihood of the transmission of parasites to themselves and allows females to select for parasite-free males. This set of olfactory and mate choice responses can be further modulated by social factors such as previous experience and exposure to infected males and the mate choices of other females. Male mice, who also face the threat of infection, similarly distinguish and avoid parasitized individuals by odor, thus reducing their likelihood of infection. This recognition and avoidance of the odors of infected individuals involves genes for the neuropeptide, oxytocin (OT), and estrogenic mechanisms. Mice with deletions of the oxytocin gene [OT knockout mice (OTKO)] and mice whose genes for estrogen receptor (ER)-alpha or ER-beta have been disrupted [ER knockout mice (ERKO), alpha-ERKO and beta-ERKO] are specifically impaired in their recognition of, aversion to, and memory of the odors of infected individuals. These findings reveal some of the genes involved in the mediation of social recognition in the ecologically relevant context of parasite recognition and avoidance.

Animals↗

PubMed2004

Genetic influences on aggressive behaviors and arousability in animals.

In a variety of species, strain differences in aggressive behaviors strongly indicate genetic influences. In people, as suggested, for example, by the work of Kagan, Rothbart, Cloninger, and their collaborators, long-lasting differences in temperament argue for genetic as well as environmental effects. After well-controlled experimentation in mice, we have learned five lessons about gene/behavior causal relations bearing on sociosexual and aggressive behaviors. The effect of a given gene on a given behavior depends upon: (1) exactly when and where that gene is expressed in the brain; (2) the gender of the animal in which it is expressed; (3) the age of the animal; (4) the nature of the opponent; and (5) the form of aggression (e.g., testosterone-facilitated aggression vs. maternal aggression). Moreover, in female mice, better social recognition is correlated with lower levels of aggression. We have gathered evidence for a four-gene micronet involving estrogen receptors alpha and beta, oxytocin, and the oxytocin receptor as expressed in the hypothalamus and amygdala. Normal performance of this micronet is required for social recognition and thus for control over aggression. Underlying certain genetic influences on sociosexual behaviors and aggression may be alterations in generalized brain arousal.

Aggression↗

PubMed2003

Effects of magnetic field exposure on open field behaviour and nociceptive responses in mice.

Results of previous studies have shown that nociceptive sensitivity in male C57 mice is enhanced by exposure to a regular 37 Hz or an irregularly varying (<1 Hz) electromagnetic field. In order to test whether these fields affect more generally mouse behaviour, we placed Swiss CD-1 mice in a novel environment (open field test) and exposed them for 2 h to these two different magnetic field conditions. Hence, we analysed how duration and time course of various behavioural patterns (i.e. exploration, rear, edge chew, self-groom, sit, walk and sleep) and nociceptive sensitivity had been affected by such exposure. Nociceptive sensitivity was significantly greater in magnetically treated mice than in controls. The overall time spent in exploratory activities was significantly shorter in both magnetically treated groups (< 1 Hz, 33% and 37 Hz, 29% of total time), than in controls (42%). Conversely, the time spent in sleeping was markedly longer in the treated groups (both 27% of total time) than in controls (11%). These results suggest that exposure to altered magnetic fields induce a more rapid habituation to a novel environment.

Animals↗

PubMed2003

An estrogen-dependent four-gene micronet regulating social recognition: a study with oxytocin and estrogen receptor-alpha and -beta knockout mice.

Estrogens control many physiological and behavioral processes, some of which are connected to reproduction. These include sexual and other social behaviors. Here we implicate four gene products in a micronet required for mammalian social recognition, through which an individual learns to recognize other individuals. Female mice whose genes for the neuropeptide oxytocin (OT) or the estrogen receptor (ER)-beta or ER-alpha had been selectively "knocked out" were deficient specifically in social recognition and social anxiety. There was a remarkable parallelism among results from three separate gene knockouts. The data strongly suggest the involvement in social recognition of the four genes coding for ER-alpha, ER-beta, OT, and the OT receptor. We thus propose here a four-gene micronet, which links hypothalamic and limbic forebrain neurons in the estrogen control over the OT regulation of social recognition. In our model, estrogens act on the OT system at two levels: through ER-beta, they regulate the production of OT in the hypothalamic paraventricular nucleus, and through ER-alpha, they drive the transcription of the OT receptor in the amygdala. The proper operation of a social recognition mechanism allows for the expression of appropriate social behaviors, aggressive or affiliative.

Animals↗

PubMed2002

Estradiol differentially regulates lipocalin-type prostaglandin D synthase transcript levels in the rodent brain: Evidence from high-density oligonucleotide arrays and in situ hybridization.

Microarrays comprise an efficient approach to discovering large numbers of differentially expressed mRNA transcripts in the CNS resulting from changes in hormonal milieu. We used high-density oligonucleotide microarrays to examine the short- and long-term actions of estradiol (E(2)) on the transcriptomes from the medial basal hypothalamus and other brain regions of E(2)-treated (10 microg) adult female mice. Our results have revealed several unanticipated gene regulations. Most striking is lipocalin prostaglandin D(2) synthase (L-PGDS), which catalyzes the conversion of prostaglandin (PG) H(2) to PGD(2), a neuromodulator involved in a variety of functions, including sleep, pain, and odor responses. In situ hybridization revealed significant increases in L-PGDS expression in the arcuate and ventromedial nucleus of the medial basal hypothalamus compared with vehicle controls. The magnitude of these changes is approximately 2-fold and suggests a modulatory role for PGD(2) in E(2)-controlled neuroendocrine secretions and behaviors. Surprisingly, L-PGDS gene expression is reduced 2-fold after E(2) treatment in the ventrolateral preoptic area (VLPO), the suspected site of action for the sleep-promoting effects of PGD(2). Finally, whereas L-PGDS has been reported to be expressed primarily in oligodendrocytes of the adult rodent brain, we demonstrate, immunocytochemically, that L-PGDS is also expressed in a population of VLPO neurons. Thus, our data suggest the intriguing possibility that E(2) modulation of L-PGDS plays a role in the regulation of sleep-wake states through hitherto unknown mechanisms in VLPO neurons and through hormone-dependent neuronal-glial cooperation.

Animals↗

PubMed1998

Sex differences in opioid and N-methyl-D-aspartate mediated non-opioid biting fly exposure induced analgesia in deer mice.

There is evidence for sex differences in responses to noxious stimuli and in the expression and mediation of analgesia. In particular, results of investigations with swim stress and the more ethologically appropriate stress of predator odor exposure have suggested sex differences in N-methyl-D-aspartate (NMDA) receptor system involvement in the mediation of analgesia. Whether or not this sex difference generalizes to other environmental stressors is, however, not clear. Biting flies are a natural aversive stimuli commonly encountered by wild and domestic animals and humans. The present study examined the opioid and non-opioid mediated nociceptive (50 degrees C hot plate) responses of reproductive male and female deer mice, Peromyscus maniculatus, exposed to biting fly attack. A 30 min exposure to biting flies (stable flies, Stomoxys calcitrans (L.)) elicited a naloxone sensitive, opioid-mediated analgesia that was of a greater magnitude in males than in female deer mice. In contrast, a 5 min exposure to biting flies elicited a 'on-opioid' analgesia that was of similar magnitude in both sexes and insensitive to both naloxone and the specific kappa opiate antagonist, nor-binaltorphimine. In male mice this non-opioid analgesia was antagonised by the competitive NMDA antagonist, NPC 1262, while in reproductive females the biting fly-induced analgesia was insensitive to NPC 12626. These results show that there are sex differences in NMDA involvement in the mediation of the non-opioid analgesia arising from brief exposure to the stress of biting fly attack. These data from a common, natural environmental challenge support the presence of basic sex difference in NMDA involvement in the mediation of stress-induced analgesia.

Amino Acids↗