The Experts below are selected from a list of 15969 Experts worldwide ranked by ideXlab platform
Richard Kinkead - One of the best experts on this subject based on the ideXlab platform.
-
The influence of sex and Neonatal Stress on medullary microglia in rat pups.
Experimental physiology, 2018Co-Authors: Cécile Baldy, Stéphanie Fournier, Samuel Boisjoly-villeneuve, Marie-Ève Tremblay, Richard KinkeadAbstract:NEW FINDINGS What is the central question of the study? Does Neonatal Stress, in the form of Neonatal maternal separation, influence the maturation of microglial density, morphology and neuronal signalling in medullary regions regulating cardiorespiratory function in rat pups? What is the main finding and its importance? Using Iba-1 immunohistochemistry, we show that Neonatal maternal separation augments microglial density and the proportion of cells with an amoeboid morphology in the medulla. Although the current understanding of the effect of early life Stress on medullary development is relatively limited, these data show that within this area, microglia are affected by Neonatal Stress. Microglia could therefore be important effectors in cardiorespiratory disorders resulting from maternal separation. ABSTRACT Neonatal Stress has wide-ranging consequences for the developing brain, including the medullary cardiorespiratory network. In rat pups, the reflexive cardiorespiratory inhibition triggered by the presence of liquids near the larynx is augmented by Neonatal maternal separation (NMS), especially in males. Sex-specific enhancement of synaptic connectivity by NMS might explain this cardiorespiratory dysfunction. Microglia influence the formation, maturation, activity and elimination of developing synapses, but their role in the wiring of medullary networks is unknown. Owing to their sensitivity to sex hormones and Stress hormones, microglial dysfunction could contribute to the abnormal cardiorespiratory phenotype observed in NMS pups. Here, we first used ionized calcium-binding adapter molecule-1 (Iba-1) immunolabelling to compare the density and morphology of microglia in the medulla of male versus female rat pups (14-15 days old) that were either undisturbed or subjected to NMS (3 h day-1 ; postnatal days 3-12). Neonatal maternal separation augmented the density of Iba-1+ cells (caudal region of the NTS), increased the size of the soma and reduced the arborization area (especially in the dorsal motor nucleus of the vagus). Sex-based differences were not observed. Given that the actions of microglia are regulated by neuronal fractalkine (CX3 CL1 ), we then used western blot analysis to compare the expression of CX3 CL1 and its microglial receptor (CX3 CR1 ) in medullary homogenates from control and NMS pups. Although CX3 CR1 expression was 59% greater in males versus females, NMS had no effect on CX3 CL1 /CX3 CR1 signalling. Given that an amoeboid morphology reflects an immature phenotype in developing microglia, NMS could interfere with synaptic pruning via a different mechanism.
-
Neonatal Stress affects the aging trajectory of female rats on the endocrine, temperature, and ventilatory responses to hypoxia
American journal of physiology. Regulatory integrative and comparative physiology, 2015Co-Authors: Stéphanie Fournier, Roumiana Gulemetova, Cécile Baldy, Vincent Joseph, Richard KinkeadAbstract:Human and animal studies on sleep-disordered breathing and respiratory regulation show that the effects of sex hormones are heterogeneous. Because Neonatal Stress results in sex-specific disruption...
-
The effects of sex and Neonatal Stress on pituitary adenylate cyclase-activating peptide expression.
Experimental physiology, 2015Co-Authors: E. V. Mosca, Roumiana Gulemetova, Richard Kinkead, Jean-philippe Rousseau, Richard J. A. WilsonAbstract:New Findings What is the central question of this study? Does sex or Neonatal Stress affect the expression of pituitary adenylate cyclase-activating peptide or its receptors? What is the main finding and its importance? Neonatal–maternal separation Stress has little long-lasting effect on the expression of pituitary adenylate cyclase-activating peptide or its receptors, but sex differences exist in these genes between males and females at baseline. Sex differences in classic Stress hormones have been studied in depth, but pituitary adenylate cyclase-activating peptide (PACAP), recently identified as playing a critical role in the Stress axes, has not. Here we studied whether baseline levels of PACAP differ between sexes in various Stress-related tissues and whether Neonatal–maternal separation Stress has a sex-dependent effect on PACAP gene expression in Stress pathways. Using quantitative RT-PCR, we found sex differences in PACAP and PACAP receptor gene expression in several respiratory and/or Stress-related tissues, while Neonatal–maternal separation Stress did little to affect PACAP signalling in adult animals. We propose that sex differences in PACAP expression are likely to contribute to differences between males and females in responses to Stress.
-
Testosterone potentiates the hypoxic ventilatory response of adult male rats subjected to Neonatal Stress.
Experimental physiology, 2014Co-Authors: Stéphanie Fournier, Roumiana Gulemetova, Vincent Joseph, Richard KinkeadAbstract:New Findings What is the central question of this study? Does testosterone contribute to the enhancement of the hypoxic ventilatory response observed in Stressed rats? What is the main finding and its importance? Castration reduces the hypoxic ventilatory response of Stressed rats (but not control rats). Neonatal Stress disrupts the gonadotrophic axis and its impact on respiratory control. These results bring new insight into the pathophysiology of sleep-disordered breathing and the sex-based difference in its prevalence. Neonatal Stress disrupts development of homeostatic systems. During adulthood, male rats subjected to Neonatal maternal separation (NMS) are hypertensive and show a larger hypoxic ventilatory response (HVR), with greater respiratory instability during sleep. Neonatal Stress also affects sex hormone secretion; hypoxia increases circulating testosterone of NMS (but not control) male rats. Given that these effects of NMS are not observed in females, we tested the hypothesis that testosterone elevation is necessary for the Stress-related increase of the HVR in adult male rats. Pups subjected to NMS were placed in an incubator for 3 h per day from postnatal day 3 to 12. Control pups remained undisturbed. Rats were reared until adulthood, and the HVR was measured by plethysmography (fractional inspired O2 = 0.12, for 20 min). We used gonadectomy to evaluate the effects of reducing testosterone on the HVR. Gonadectomy had no effect on the HVR of control animals but reduced that of NMS animals below control levels. Immunohistochemistry was used to quantify androgen receptors in brainstem areas involved in the HVR. Androgen receptor expression was generally greater in NMS rats than in control rats; the most significant increase was noted in the caudal region of the nucleus tractus solitarii. We conclude that the abnormal regulation of testosterone is important in Stress-related augmentation of the HVR. The greater number of androgen receptors within the brainstem may explain why NMS rats are more sensitive to testosterone withdrawal. Based on the similarities of the cardiorespiratory phenotype of NMS rats and patients suffering from sleep-disordered breathing, these results provide new insight into its pathophysiology, especially sex-based differences in its prevalence.
-
Neonatal Stress augments the hypoxic chemoreflex of adult male rats by increasing AMPA receptor‐mediated modulation
Experimental physiology, 2013Co-Authors: Roumiana Gulemetova, Guy Drolet, Richard KinkeadAbstract:New Findings • What is the central question of this study?Early life exposure to Stress augments the hypoxic chemoreflex of adult male rats. This effect predisposes to respiratory instability during sleep. We used pharmacological and neuroanatomical approaches to determine whether a change in glutamatergic neurotransmission contributes to this abnormal respiratory phenotype. • What is the main finding and its importance?We initially showed that Neonatal Stress augments sensitivity to an AMPA/kainate receptor antagonist. Results from autoradiography experiments support this observation because they demonstrate that Neonatal Stress increases expression of AMPA receptors in key regions that regulate breathing. Region-specific changes in brain-derived neurotrophic factor expression may contribute to these changes in glutamatergic neurotransmission. These results bring new insight into the pathophysiology of sleep-disordered breathing. Neonatal Stress disrupts the developmental trajectory of homeostatic systems. Adult (8- to 10-week-old) male rats exposed to maternal separation (a form of Neonatal Stress) display several traits reported in patients suffering from sleep-disordered breathing, including an augmented hypoxic chemoreflex. To understand the mechanisms behind this effect, we tested the hypothesis that Neonatal Stress augments glutamatergic neurotransmission in three regions involved in respiratory regulation, namely the nucleus of the solitary tract, the paraventricular nucleus of the hypothalamus and the phrenic motor nucleus. Maternal separation was performed for 3 h day−1 from postnatal day 3 to 12. Control pups were undisturbed. Adult rats were instrumented for intracerebroventricular injection of the AMPA/kainate receptor antagonist CNQX (0–4.3 μm). Using plethysmography, ventilatory activity was measured at rest in awake animals during normoxia (fractional inspired O2= 0.21) and during acute hypoxia (fractional inspired O2= 0.12; 20 min). Following vehicle injection, the hypoxic ventilatory response of Stressed rats was 35% greater than that of controls. Microinjection of CNQX attenuated the hypoxic ventilatory response, but the effect observed in Stressed rats was greater than that in control animals. Autoradiography experiments showed that Neonatal Stress augments expression of AMPA receptors within the paraventricular nucleus of the hypothalamus and the phrenic motor nucleus. Quantification of brain-derived neurotrophic factor showed that Neonatal Stress augments brain-derived neurotrophic factor expression only within the paraventricular nucleus. We conclude that Neonatal Stress augments the hypoxic chemoreflex by increasing the efficacy of glutamatergic synaptic inputs projecting onto key respiratory structures, especially the paraventricular nucleus of the hypothalamus. These data provide new insight into the aetiology of sleep-disordered breathing.
Ronit Avitsur - One of the best experts on this subject based on the ideXlab platform.
-
Neonatal Stress modulates sickness behavior: role for proinflammatory cytokines.
Journal of Neuroimmunology, 2013Co-Authors: Ronit Avitsur, Rachel Maayan, Abraham WeizmanAbstract:Neonatal Stress increased the duration and augmented symptoms of sickness behavior induced by influenza virus infection or endotoxin challenge in mice. Since proinflammatory cytokines were implicated in sickness behavior, the present study sought to determine the effect of Neonatal Stress on cytokines-induced sickness behavior and on proinflammatory cytokine secretion. Data indicate that separation of mouse pups from the dams at an early age (maternal separation, MSP) increased the duration and augmented some of the symptoms of sickness behavior induced by proinflammatory cytokines. In addition, MSP partially suppressed cytokine and corticosterone secretion in response to endotoxin administration. These data may suggest that MSP increased sensitivity to the effects of proinflammatory cytokines on sickness behavior following an immune challenge.
-
Neonatal Stress modulates sickness behavior.
Brain behavior and immunity, 2009Co-Authors: Ronit Avitsur, John F SheridanAbstract:The quality of the early environment, especially during the Neonatal period, influences the development of individual differences in resistance to Stress and illness in adulthood. A previous study demonstrated that Neonatal Stress augmented proinflammatory cytokine expression and viral replication in influenza virus-infected adult mice. The goal of the following study was to examine the lifelong effects of Neonatal Stress on the behavioral response to an immune challenge. Neonatal Stress consisted of separating mouse pups from their dams (maternal separation, MSP) at critical points of their development. In the first study, pups were separated from the dam daily for 6 h between postnatal day 1 and 14. As adults, these mice were infected with influenza A/PR8 virus. In a second study, a similar paradigm of MSP was employed, and as adults mice were injected with lipopolysaccharide (LPS) (ip). In a third study pups were separated from the dam for 24 h on postnatal day 4 or 9. As adults, these mice received ip injections of LPS. In all three studies, changes in body weight, food and sweet solution consumption were examined following immune challenge. As previously described, activation of the immune system using influenza virus infection or LPS administration resulted in sickness behavior that consisted of body weight loss, anorexia and reduced consumption of a sweet solution. Furthermore, Neonatal Stress induced more rapid kinetics of sickness behavior and augmented several aspects of these symptoms. Together with previous studies, these findings suggest that Neonatal Stress disrupted the regulation of innate resistance to an immune challenge resulting in enhanced immunological and behavioral responses to immune activation. Thus, long lasting effects of early Stress events may be the basis for individual differences in health and susceptibility to disease.
María J. Ramírez - One of the best experts on this subject based on the ideXlab platform.
-
Venlafaxine reverses decreased proliferation in the subventricular zone in a rat model of early life Stress.
Behavioural brain research, 2015Co-Authors: Eva Martisova, Bárbara Aisa, Rosa M. Tordera, Elena Puerta, Maite Solas, María J. RamírezAbstract:It is believed that glucocorticoids control the proliferation of neural progenitor cells, and this process is highly involved in mood disorders and cognitive processes. Using the maternal separation model of chronic Neonatal Stress, it has been found that Stress induced depressive-like behavior, cognitive deficits and a decrease in proliferation in the subventricular zone (SVZ). Venlafaxine reversed all deleterious effects of chronic Stress by modulating HPA activity. These outcomes suggest modulation of Stress-mediated glucocorticoid secretion as a target for the treatment of mood disorders and neurodegenerative processes.
-
Neonatal Stress affects vulnerability of cholinergic neurons and cognition in the rat: involvement of the HPA axis.
Psychoneuroendocrinology, 2009Co-Authors: Bárbara Aisa, Rosa M. Tordera, Berta Lasheras, Joaquín Del Río, Francisco J. Gil-bea, Beatriz Marcos, María J. RamírezAbstract:Adverse experiences early in life may sensitize specific neurocircuits to subsequent Stressors. We have evaluated in maternal separation (MS) rats, an animal paradigm of early-life Stress, the effects of a selective cholinergic lesion on cognitive function as well as susceptibility of cholinergic neurons to the lesion. MS rats subjected to a cholinergic lesion by administration of the immunotoxin 192 IgG-saporin, showed significant decreases in both choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activity compared to control lesioned rats. Morris water maze results revealed a significant impairment in learning and memory function in MS adult rats and further cognitive deficits after the lesion. The lesion of cholinergic neurons induced a significant decrease in glucocorticoid receptor density in MS rats, accompanied by increases in CRF mRNA expression. Decreases in NGF and increases in NGF-p75NTR expression have also been found in MS rats. Our results suggest that vulnerability of basal forebrain cholinergic nerve cells might be affected by the HPA axis. The present data are discussed not only in terms of conditions that occur during ageing or Alzheimer disease, but also regarding a purported involvement of the cholinergic system in the regulation of HPA axis activity.
-
Effects of Neonatal Stress on markers of synaptic plasticity in the hippocampus: implications for spatial memory.
Hippocampus, 2009Co-Authors: Bárbara Aisa, N. Elizalde, Rosa M. Tordera, Berta Lasheras, Joaquín Del Río, María J. RamírezAbstract:Early Stressful adverse situations may increase the vulnerability to cognitive deficits and psychiatric disorders, such as depression. Maternal separation (MS) has been used as an animal model to study changes in neurochemistry and behavior associated with exposure to early-life Stress. This study investigated the effects of Neonatal Stress (MS) on the expression of synaptic plasticity markers in the hippocampus and a purported relationship to cognitive processes. Spatial learning (Morris water maze) significantly increased the expression of total levels of the neural cell adhesion molecule (NCAM), as well as its three major isoforms (NCAM-120, -140, and -180) both in the control and MS groups. Interestingly, these increases in NCAM expression after learning were lower in MS animals when compared with control rats. MS induced a significant decrease in total levels of NCAM, and specifically, in the NCAM-140 isoform expression. In the hippocampus of MS rats there was a significant decrease in brain-derived neurotrophic factor and synaptophysin mRNA densities. Cell proliferation, measured as BrdU-positive cells, was also decreased in the dentate gyrus of MS rats. Altogether these results suggest that MS can alter normal brain development, providing a potential mechanism by which early environmental Stressors may influence vulnerability to show cognitive impairments later in life. © 2009 Wiley-Liss, Inc.
Abraham Weizman - One of the best experts on this subject based on the ideXlab platform.
-
Neonatal Stress modulates sickness behavior: role for proinflammatory cytokines.
Journal of Neuroimmunology, 2013Co-Authors: Ronit Avitsur, Rachel Maayan, Abraham WeizmanAbstract:Neonatal Stress increased the duration and augmented symptoms of sickness behavior induced by influenza virus infection or endotoxin challenge in mice. Since proinflammatory cytokines were implicated in sickness behavior, the present study sought to determine the effect of Neonatal Stress on cytokines-induced sickness behavior and on proinflammatory cytokine secretion. Data indicate that separation of mouse pups from the dams at an early age (maternal separation, MSP) increased the duration and augmented some of the symptoms of sickness behavior induced by proinflammatory cytokines. In addition, MSP partially suppressed cytokine and corticosterone secretion in response to endotoxin administration. These data may suggest that MSP increased sensitivity to the effects of proinflammatory cytokines on sickness behavior following an immune challenge.
John F Sheridan - One of the best experts on this subject based on the ideXlab platform.
-
Neonatal Stress modulates sickness behavior.
Brain behavior and immunity, 2009Co-Authors: Ronit Avitsur, John F SheridanAbstract:The quality of the early environment, especially during the Neonatal period, influences the development of individual differences in resistance to Stress and illness in adulthood. A previous study demonstrated that Neonatal Stress augmented proinflammatory cytokine expression and viral replication in influenza virus-infected adult mice. The goal of the following study was to examine the lifelong effects of Neonatal Stress on the behavioral response to an immune challenge. Neonatal Stress consisted of separating mouse pups from their dams (maternal separation, MSP) at critical points of their development. In the first study, pups were separated from the dam daily for 6 h between postnatal day 1 and 14. As adults, these mice were infected with influenza A/PR8 virus. In a second study, a similar paradigm of MSP was employed, and as adults mice were injected with lipopolysaccharide (LPS) (ip). In a third study pups were separated from the dam for 24 h on postnatal day 4 or 9. As adults, these mice received ip injections of LPS. In all three studies, changes in body weight, food and sweet solution consumption were examined following immune challenge. As previously described, activation of the immune system using influenza virus infection or LPS administration resulted in sickness behavior that consisted of body weight loss, anorexia and reduced consumption of a sweet solution. Furthermore, Neonatal Stress induced more rapid kinetics of sickness behavior and augmented several aspects of these symptoms. Together with previous studies, these findings suggest that Neonatal Stress disrupted the regulation of innate resistance to an immune challenge resulting in enhanced immunological and behavioral responses to immune activation. Thus, long lasting effects of early Stress events may be the basis for individual differences in health and susceptibility to disease.
