Long-term ovariectomy changes formalin-induced licking in female rats: the role of estrogens
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Cholinergic neurons located in the medial septum and the diagonal band of Broca are a major source of cholinergic innervation to the hippocampal formation. These neurons play an important role in learning and memory processes [1]. Gonadal... more
Cholinergic neurons located in the medial septum and the diagonal band of Broca are a major source of cholinergic innervation to the hippocampal formation. These neurons play an important role in learning and memory processes [1]. Gonadal hormones can significantly affect the function of these cholinergic neurons [2]. Estrogens were found to increase cholineacetyltransferase (ChAT) activity and the number of ChAT neurons in the medial septum in ovariectomized female rats [3]. Moreover, estrogens significantly improve cognition capacities in menopausal women treated with estrogen-replacement therapy [4]. Although not a limiting factor in the synthesis of ACh, ChAT activity is considered an index of cholinergic activation [5]. We have previously shown that a persistent, painful stimulus (for-malin test) decreases ChAT activity in male rats, an effect not present in females [6], and induces higher c-Fos expression levels in the hippocampus of female rats than in males [7].
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Beta-caryophyllene (BCP) and docosahexaenoic acid (DHA) are components of several plants with documented anti-inflammatory and analgesic effects in animal pain models. In the present study,in vitroandin vivotests were carried out to... more
Beta-caryophyllene (BCP) and docosahexaenoic acid (DHA) are components of several plants with documented anti-inflammatory and analgesic effects in animal pain models. In the present study,in vitroandin vivotests were carried out to evaluate their effects, alone or in combination, during long-lasting administration in a model of persistent pain. IR spectra of the two compounds were obtained to determine their chemical stability and thenin vitrotoxicity was evaluated in fibroblasts and astrocytes. In thein vivotests, the analgesic effects of BCP and BCP+DHA were determined in male rats subjected to a model of persistent recurrent pain (three repetitions of the formalin test once a week) to mimic recurrent pain. Both substances were administeredper osin almond oil for 2 weeks. Gonadal hormones were determined at the end of the tests to evaluate treatment-induced effects on their levels. BCP changed fibroblast and astrocyte survival in a dose-dependent manner and the effect was counter...
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Research Interests: Pain, Chronic Pain, Quality of life, Reproductive Biology, Pain Management, and 15 moreBiological Sciences, Cortisol, Prospective studies, Humans, Chronic Disease, Male, Morphine, Aged, Middle Aged, Adult, Indexation, Hormone Replacement Therapy, hypogonadism, Medical and Health Sciences, and free testosterone
Background: Besides functioning as chemosensors for a broad range of endogenous and synthetic ligands, transient receptor potential vanilloid (TRPV) 1–4 channels have also been related to capsaicin (TRPV1), pain, and thermal stimuli... more
Background: Besides functioning as chemosensors for a broad range of endogenous and synthetic ligands, transient receptor potential vanilloid (TRPV) 1–4 channels have also been related to capsaicin (TRPV1), pain, and thermal stimuli perception, and itching sensation (TRPV1–4). While the expression of the TRPV1–4 genes has been adequately proved in skin, sensory fibres and keratinocytes, less is known about TRPV3 and TRPV4 expression in human blood cells. Results: To study the gene expression of TRPV1–4 genes in human leukocytes, a quantitative Real-Time PCR (qRT-PCR) method, based on the calculation of their relative expression, has been developed and validated. The four commonly used house-keeping genes (HKGs), β-Actin (Act-B), glyceraldehyde-3P-dehydrogenase (GAPDH), hypoxanthine ribosyltransferase (HPRT1), and cyclophilin B (hCyPB), were tested for the stability of their expression in several human leukocyte samples, and used in the normalization procedure to determine the mRNA l...
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Background: The steroid hormone testosterone has been found to be greatly reduced by opioids in different experimental and clinical conditions. The purpose of this study on male rats was to determine the effects of a single injection of... more
Background: The steroid hormone testosterone has been found to be greatly reduced by opioids in different experimental and clinical conditions. The purpose of this study on male rats was to determine the effects of a single injection of morphine (5 mg/Kg) on persistent pain (formalin test) and the single or combined effects on p450-aromatase and 5-alpha reductase type 1 mRNA expression in the brain, liver and testis. Testosterone was determined in the plasma and in the brain, morphine was assayed in the plasma. Results: In the morphine-treated rats, there were increases of 5-alpha reductase mRNA expression in the liver and aromatase mRNA expression in the brain and gonads. Morphine was detected in the blood of all morphine-treated rats even though there were no clear analgesic affects in the formalin-treated animals three hours after treatment. Testosterone was greatly reduced in the plasma and brain in morphine-treated subjects. Conclusions: It appears that morphine administration ...
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The aim of the present study was to evaluate the effect of an exhaustive exercise on platelet adhesion and aggregation on polyethylene (PE) in relation to changes in plasma cortisol concentration in order to ascertain the effect of... more
The aim of the present study was to evaluate the effect of an exhaustive exercise on platelet adhesion and aggregation on polyethylene (PE) in relation to changes in plasma cortisol concentration in order to ascertain the effect of physical stress response in the blood-contacting properties of polymeric materials. Twelve healthy sedentary subjects, six males and six females, were studied. Each subject performed an exercise test on a bicycle ergometer at intensity corresponding to 70% VO2 max until exhaustion. One month after the exercise session, each subject participated in a control rest session. In both sessions, blood samples were drawn every 5 min for cortisol, lactate, hemoglobin, and hematocrit determinations and every 15 min for evaluation of platelet adhesion and aggregation. Individual comparisons between the rest and exercise cortisol patterns identified three categories of cortisol responders to exercise: positive responders (C +, showing higher concentrations during exercise than during rest), negative responders (C -, showing lower concentrations during exercise than during rest), and nonresponders (NR, showing similar concentrations during exercise and rest). The results revealed that C + had lower platelet adhesion and aggregation scores during exercise than during rest; moreover C - had higher scores than C + and NR during exercise. The results obtained demonstrated no effects of sex or exercise on either cortisol plasma levels or platelet adhesion and aggregation on PE surface. With regard to cardiovascular risk, the results suggest that exercise favorably affects platelet functions when mechanisms of metabolic adaptation to prolonged muscular work, expressed by a cortisol increase, are activated during exercise.
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Menopause is the last step in the reproductive history of a woman. The ovaries stop producing hormones and the body reacts by lowering its functions, including the neuronal one. Phytoestrogens are plant products with estrogen-like... more
Menopause is the last step in the reproductive history of a woman. The ovaries stop producing hormones and the body reacts by lowering its functions, including the neuronal one. Phytoestrogens are plant products with estrogen-like activity able to affect many body functions. The aim of the present experiment was to study the effects of 30 days of regular consumption of a soy-enriched bread containing a known amount of phytoestrogens (genistein and daidzein). Women at climacteric, within 5 years or more than 5 years of menopause, were asked to include in their diet 200 g/day of a bread containing 40 mg of phytoestrogens. The effect on common menopausal symptoms and neurophysiological, hormonal and antioxidant parameters were determined before and after 30 days through questionnaires and experimental tests. Phytoestrogens were measured in the urine. In all groups, there was a significant increase of phytoestrogens in the urine and a decrease of the classical symptoms of menopause as w...
The effects of two environmental endocrine disruptors, the synthetic pharmaceutical estrogen 17-ethinylestradiol (EE) and bisphenol-A (BPA), were analysed in male and female rats in a very sensitive developmental period, puberty.... more
The effects of two environmental endocrine disruptors, the synthetic pharmaceutical estrogen 17-ethinylestradiol (EE) and bisphenol-A (BPA), were analysed in male and female rats in a very sensitive developmental period, puberty. Immunohistochemistry was used to evaluate changes in the number of cells expressing estrogen receptors (ER-alpha) in the arcuate nucleus (ARC), ventromedial nucleus (VMH) and medial preoptic area (MPA) of the hypothalamus. Animals were treated during early puberty, from PND 23 to PND 30, with EE and BPA given orally every day. They were then sacrificed and perfused on PND 37 or PND 90, and blood and brains were collected for hormonal determination (testosterone and estradiol) and immunohistochemistry (estrogen receptors, ER). At PND 37, ER-labelled neurons were higher in males than in females in the ARC and MPA. EE and BPA increased ER-labelled neurons in the ARC and MPA. At PND 90, females showed higher ER-labelled neurons in the VMH. EE and BPA increased ER-labelled neurons in the MPA in females. EE increased testosterone in males at PND 37 and estradiol in females at PND 90. These results indicate the ability of estrogenic chemicals to change the reproductive neural circuits during puberty in male and female rats.
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Research Interests: Psychology, Cognitive Science, Immunohistochemistry, Lactation, Estrogen Receptor, and 15 moreBrain Mapping, bisphenol A, Female, Animals, Arcuate Nucleus, Estrogen Receptors, Phenols, Rats, Rat, Brain Chemistry, Neurosciences, Estrous cycle, Estrogen receptor alpha, Medial Preoptic Area, and Cell count
The modulation of acetylcholine (ACh) release by 5-HT3 receptor activation was studied using in vivo microdialysis. Spontaneous and K+-stimulated ACh release were measured in frontoparietal cortex and hippocampus of freely moving rats.... more
The modulation of acetylcholine (ACh) release by 5-HT3 receptor activation was studied using in vivo microdialysis. Spontaneous and K+-stimulated ACh release were measured in frontoparietal cortex and hippocampus of freely moving rats. Two consecutive exposures to high K+ produced ACh release of similar magnitude. In the cortex, serotonin (5-HT) failed to alter spontaneous ACh release, but caused a concentration-dependent decrease of K+-evoked ACh release. Phenylbiguanide (PBG) and m-chlorophenylbiguanide, two selective 5-HT3 agonists, mimicked the 5-HT responses, but 8-hydroxy-2-(di-n-propylamino)tetralin, a selective 5-HT1A agonist, was without effect. However, PBG failed to modify K+-evoked ACh release from the hippocampus. Systemic and local administration of a highly selective 5-HT3 antagonist, tropisetron ((3-alpha-tropanyl)1H-indole-carboxylic acid ester) blocked the effect of both 5-HT and PBG. The inhibition of ACh release by PBG was sensitive to tetrodotoxin. These observations provide direct evidence that, in rat cortex, 5-HT modulates in-vivo release of ACh through activation of 5-HT3 receptors.
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The effects of two environmental endocrine disruptors, the synthetic pharmaceutical estrogen 17-ethinylestradiol (EE) and bisphenol-A (BPA), were analysed in male and female rats in a very sensitive developmental period, puberty.... more
The effects of two environmental endocrine disruptors, the synthetic pharmaceutical estrogen 17-ethinylestradiol (EE) and bisphenol-A (BPA), were analysed in male and female rats in a very sensitive developmental period, puberty. Immunohistochemistry was used to evaluate changes in the number of cells expressing estrogen receptors (ER-α) in the arcuate nucleus (ARC), ventromedial nucleus (VMH) and medial preoptic area (MPA) of the hypothalamus. Animals were treated during early puberty, from PND 23 to PND 30, with EE and BPA given orally every day. They were then sacrificed and perfused on PND 37 or PND 90, and blood and brains were collected for hormonal determination (testosterone and estradiol) and immunohistochemistry (estrogen receptors, ER). At PND 37, ER-labelled neurons were higher in males than in females in the ARC and MPA. EE and BPA increased ER-labelled neurons in the ARC and MPA. At PND 90, females showed higher ER-labelled neurons in the VMH. EE and BPA increased ER-labelled neurons in the MPA in females. EE increased testosterone in males at PND 37 and estradiol in females at PND 90. These results indicate the ability of estrogenic chemicals to change the reproductive neural circuits during puberty in male and female rats.
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17α-Ethinylestradiol (EE), the main component of the contraceptive pill, is a synthetic estrogen found in rivers of the United States and Europe as an environmental contaminant. It is one of the most studied xenoestrogens due to its... more
17α-Ethinylestradiol (EE), the main component of the contraceptive pill, is a synthetic estrogen found in rivers of the United States and Europe as an environmental contaminant. It is one of the most studied xenoestrogens due to its possible effect on the reproductive system. In the present study we evaluated the modulation of pain responses induced by formalin injection (licking, flexing, paw-jerk) in 8-month-old male and female offspring of female rats treated with two different doses of EE (4ng/kg/day or 400ng/kg/day) during pregnancy and lactation. Spontaneous behaviors and gonadal hormone levels were also determined. Both concentrations of EE induced an increase of pain behaviors in males only, i.e. higher flexing and licking of the formalin-injected paw than in OIL-exposed rats, during the second, inflammatory, phase of the formalin test. Grooming duration was increased by EE exposure in both males and females. Prenatal EE exposure (both concentrations) decreased estradiol plasma levels in the formalin-injected females but not in the males. These results underline the possibility that exposure to an environmental contaminant during the critical period of development can affect neural processes (such as those involved in pain modulation) during adulthood, indicating long-term changes in brain circuitry. However, such changes may be different in males and females.
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Gonadal hormones have been shown to exert modulatory effects on nociception and analgesia. To investigate the role of gonadal hormones in the response by female rats to both phasic and persistent nociceptive stimulation, we evaluated the... more
Gonadal hormones have been shown to exert modulatory effects on nociception and analgesia. To investigate the role of gonadal hormones in the response by female rats to both phasic and persistent nociceptive stimulation, we evaluated the effects of long-term ovariectomy (OVX, 6 months) on the thermal pain threshold and on formalin-induced responses. The thermal pain threshold was evaluated with the plantar test apparatus, while persistent pain was induced by a subcutaneous injection of dilute formalin (50 microliter, 10%) in the dorsal hind paw. The formalin test was carried out in an open field apparatus where the animal's spontaneous behavior and formalin-induced responses (licking duration, flinching frequency and flexing duration of the injected paw) were recorded for 60 min. Estradiol and corticosterone plasma levels were determined in blood collected from the anesthetized animals at the end of the test. In OVX females, the duration of formalin-induced licking was longer th...
Research Interests: Pain, Biological Sciences, Brain, Female, Animals, and 14 moreSpinal Cord, Corticosterone, Open Field, Molecular endocrinology and reproductive biology, Estrogens, Rats, Formaldehyde, Pain Measurement, Estradiol, Hyperalgesia, Pain Threshold, Formalin Test, Ovariectomy, and Medical and Health Sciences
Women have a higher incidence of chronic pain syndromes than men and are generally more sensitive to experimental pain. Numerous studies have shown that the female gonadal hormones, estrogens, can profoundly affect the nervous and immune... more
Women have a higher incidence of chronic pain syndromes than men and are generally more sensitive to experimental pain. Numerous studies have shown that the female gonadal hormones, estrogens, can profoundly affect the nervous and immune systems, including mechanisms involved in pain and nociception. In the present study, we used antagonists of estrogen receptors (ER) or mu-opioid receptors (mu OR) to evaluate the effects of estrogens on formalin-induced behavioural and immune responses in male rats. After two days of priming with 17 beta-estradiol or saline (i.c.v.), animals were subjected to the formalin test; 15 min prior to formalin (50 microl, 5%) or sham injection in the hind paw, animals were treated with an ER antagonist (ICI 182,780, ICI) or a mu OR antagonist (beta-funaltrexamine, FNA) or saline. The spontaneous behaviours, pain-related behaviours and interferon-gamma (IFN-gamma) production by peripheral blood mononuclear cells were studied in all groups. We found that cen...
Research Interests: Immune response, Animal Behavior, Pain, Chronic Pain, Drug interactions, and 15 moreEstrogen Receptor, Animals, Male, Immune system, Rats, Immune function, Naltrexone, Opioid Receptor, Pain Measurement, Estradiol, Formalin Test, Interferon gamma, Psychology and Cognitive Sciences, Estrogen antagonists, and Medical and Health Sciences
Women have a higher incidence of chronic pain syndromes than men and are generally more sensitive to experimental pain. Numerous studies have shown that the female gonadal hormones, estrogens, can profoundly affect the nervous and immune... more
Women have a higher incidence of chronic pain syndromes than men and are generally more sensitive to experimental pain. Numerous studies have shown that the female gonadal hormones, estrogens, can profoundly affect the nervous and immune systems, including mechanisms involved in pain and nociception. In the present study, we used antagonists of estrogen receptors (ER) or μ-opioid receptors (μOR) to
Research Interests: Immune response, Animal Behavior, Pain, Chronic Pain, Drug interactions, and 15 moreEstrogen Receptor, Animals, Male, Immune system, Rats, Immune function, Naltrexone, Opioid Receptor, Pain Measurement, Estradiol, Formalin Test, Interferon gamma, Psychology and Cognitive Sciences, Medical and Health Sciences, and Male rat
Résumé La présence de différences entre les sexes en termes de douleur est reconnue depuis longtemps. Cette étude met en évidence les nombreuses données, anciennes ou plus récentes, concernant les différences entre les sexes en termes de... more
Résumé La présence de différences entre les sexes en termes de douleur est reconnue depuis longtemps. Cette étude met en évidence les nombreuses données, anciennes ou plus récentes, concernant les différences entre les sexes en termes de douleur. Ces données concernent tout particulièrement le système limbique, notamment l’hypothalamus et l’hippocampe, avec ses effets sur la stimulation et l’attention, et confirment la
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Gonadal hormones are known to be affected by morphine and other opioids. In this paper, we summarize data collected in recent years which clearly indicate that the opioid-induced effects on steroid hormones depend on the opioid used and... more
Gonadal hormones are known to be affected by morphine and other opioids. In this paper, we summarize data collected in recent years which clearly indicate that the opioid-induced effects on steroid hormones depend on the opioid used and in some cases on the sex of the subject. Indeed morphine is able to reduce hormones like testosterone and cortisol in both male and female subjects in just a few hours, probably acting directly on peripheral glands. These depressant effects of morphine on hormones are also present in the treatment of surgical pain and are quickly reversible once opioid administration is suspended. Similar actions were also found to occur in experimental animals and in vitro in glial cells, further confirming the morphine-induced reduction of testosterone cell content. Testosterone and its metabolites are well known substances involved in the development and maintenance of the brain and all body structures. Thus when treating pain with opioids, their effects on hypothalamo-pituitary-gonadal and hypothalamo-pituitary-adrenal-related hormones must be considered and, where possible, hormone replacement therapy should be started.
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Research Interests: Pain, Behavior, Immunohistochemistry, Gene expression, Hippocampus, and 15 moreFemale, Animals, Male, Open Field, Gene, Dentate Gyrus, Gen, Analysis of Variance, Neuronal Activity, Nociception, Formaldehyde, Pain Measurement, Estrous cycle, Formalin Test, and Pharmacology and pharmaceutical sciences
Chronic pain is gender-related, since there is a clear predominance of one sex with respect to the other in most pain syndromes. Gonadal hormones are known to affect the occurrence and incidence of pain. Transsexuals receive cross-sex... more
Chronic pain is gender-related, since there is a clear predominance of one sex with respect to the other in most pain syndromes. Gonadal hormones are known to affect the occurrence and incidence of pain. Transsexuals receive cross-sex hormones to develop and maintain somatic characteristics of the opposite sex: male to female transsexuals (MtF) are administered estrogens and anti-androgens, while female to male transsexuals (FtM) are administered androgens. Hence, these subjects represent a model to study the relationship between sex hormones and pain. Questionnaires dealing with sociodemographic data and pain (occurrence, frequency, duration, intensity, location and associated symptoms) were administered to both MtF and FtM transsexuals under hormone treatment for sex reassignment for at least 1 year. Forty-seven MtF and 26 FtM completed the questionnaires. Fourteen of the 47 MtF (29.8%) reported painful conditions, which in 11 subjects were not present before the beginning of hormone treatment. Pain consisted mainly of headaches and breast and musculoskeletal pain. Five subjects suffered from more than one pain condition. Sixteen of the 26 FtM (61.5%) reported pain. In 11 subjects, the pain was present before the beginning of hormone intake, and in 6 of them it improved after testosterone administration. These data suggest that marked changes in sex hormones affect the occurrence of pain in a high percentage of humans but not in all of them. Whether these effects are due to peripheral or central actions of sex steroids is unknown.
Research Interests: Pain, Chronic Pain, Humans, Female, Headache, and 15 moreGender Relations, Male, Musculoskeletal pain, Breast, Questionnaires, Cyproterone Acetate, Adult, Musculoskeletal system, Female To Male, Pain Measurement, Estradiol, Pain Threshold, Sex Characteristics, Psychology and Cognitive Sciences, and Medical and Health Sciences
The role of gonadal hormones in inducing long-term modifications in response to transient nociceptive stimuli was investigated in adult male rats. Three weeks after gonadectomy or sham surgery, animals were randomly divided into groups to... more
The role of gonadal hormones in inducing long-term modifications in response to transient nociceptive stimuli was investigated in adult male rats. Three weeks after gonadectomy or sham surgery, animals were randomly divided into groups to be exposed to sham (only a prick in the dorsal hind paw) or formalin treatment (50 microl, 5% s.c. in the dorsal hind paw) once a week for the following 3 weeks. In gonadectomized animals the formalin-induced responses (licking, flexing and jerking of the injected paw) did not differ from those of intact animals after the first formalin injection. However, their levels were higher after the second or third injections. Indeed, in intact animals the formalin-induced responses progressively decreased, being significantly lower after the third injection than after the first; in gonadectomized animals, the formalin-induced responses did not change with repetition of the formalin treatment. In intact rats, c-Fos expression in the paraventricular nucleus of the thalamus and arcuate nucleus of the hypothalamus remained at control levels or decreased in animals injected two or three times with formalin; in gonadectomized rats, c-Fos expression increased with repetition of the noxious stimulation, reaching the highest levels in animals injected three times with formalin. These results show that male gonadal hormones have an inhibitory, adaptive effect on the behavioral and neuronal responses to repeated nociceptive stimulation.
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The effects of two environmental endocrine disruptors, the synthetic pharmaceutical estrogen 17-ethinylestradiol (EE) and bisphenol-A (BPA), were analysed in male and female rats in a very sensitive developmental period, puberty.... more
The effects of two environmental endocrine disruptors, the synthetic pharmaceutical estrogen 17-ethinylestradiol (EE) and bisphenol-A (BPA), were analysed in male and female rats in a very sensitive developmental period, puberty. Immunohistochemistry was used to evaluate changes in the number of cells expressing estrogen receptors (ER-alpha) in the arcuate nucleus (ARC), ventromedial nucleus (VMH) and medial preoptic area (MPA) of the hypothalamus. Animals were treated during early puberty, from PND 23 to PND 30, with EE and BPA given orally every day. They were then sacrificed and perfused on PND 37 or PND 90, and blood and brains were collected for hormonal determination (testosterone and estradiol) and immunohistochemistry (estrogen receptors, ER). At PND 37, ER-labelled neurons were higher in males than in females in the ARC and MPA. EE and BPA increased ER-labelled neurons in the ARC and MPA. At PND 90, females showed higher ER-labelled neurons in the VMH. EE and BPA increased ER-labelled neurons in the MPA in females. EE increased testosterone in males at PND 37 and estradiol in females at PND 90. These results indicate the ability of estrogenic chemicals to change the reproductive neural circuits during puberty in male and female rats.
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Estrogens have a variety of effects in addition to their action on reproductive structures, including permanent effects on the Central Nervous System (CNS). Therefore environmental chemicals with estrogenic activity (xenoestrogens) can... more
Estrogens have a variety of effects in addition to their action on reproductive structures, including permanent effects on the Central Nervous System (CNS). Therefore environmental chemicals with estrogenic activity (xenoestrogens) can potentially affect a number of CNS functions. In the present experiment, female rats receiving ethynylestradiol (EE) or methoxychlor (MXC) via the mothers during pregnancy (pre) or lactation (post) were tested in comparison with females born from mothers treated with OIL. The Object Recognition, Plantar and Formalin tests were carried out to evaluate the effects of these compounds on integrated functions such as memory and pain. Testosterone and estradiol plasma levels were determined by RIA. The results of the Object Recognition and Plantar tests did not differ among groups. However the groups differed in the Formalin test since flexing duration was higher in the EE- and MXC-pre groups than in the EE- and MXC-post and OIL groups. Estradiol plasma levels were higher in EE-pre than in the other groups. These results confirm the possibility that estrogen-like compounds (EE and MXC) can affect complex neural processes like pain when taken during critical stages of CNS development.
Research Interests: Cognitive Science, Pain, Cognition, Lactation, Brain development, and 15 moreMemory, Neurotoxicology, Female, Animals, Object Recognition, Central Nervous System, Exposure, Estrogens, Hormone, Memory Disorders, Neurosciences, Pain Measurement, Environmental Exposure, Pain Threshold, and Formalin Test
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Research Interests: Psychology, Cognitive Science, Immunohistochemistry, Lactation, Estrogen Receptor, and 15 moreBrain Mapping, bisphenol A, Female, Animals, Arcuate Nucleus, Estrogen Receptors, Phenols, Rats, Rat, Brain Chemistry, Neurosciences, Estrous cycle, Estrogen receptor alpha, Medial Preoptic Area, and Cell count
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α7 Nicotinic acetylcholine receptors (α7 nAChR) represent promising therapeutic candidates for the treatment of cognitive impairment associated with... more
α7 Nicotinic acetylcholine receptors (α7 nAChR) represent promising therapeutic candidates for the treatment of cognitive impairment associated with Alzheimer's disease (AD) and schizophrenia. A medicinal chemistry effort around previously reported compound 1 (SEN15924, WAY-361789) led to the identification of 12 (SEN78702, WYE-308775) a potent and selective full agonist of the α7 nAChR that demonstrated improved plasma stability, brain levels, and efficacy in behavioral cognition models.
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... Giuliano Fontani, Anna Lisa Suman, Silvia Migliorini, Fausto Corradeschi, Ilaria Ceccarelli, Annamaria Aloisi, and Giancarlo Carli ... patients exhibit lowered thresholds to experimentally induced mechanical, thermal and ischemic... more
... Giuliano Fontani, Anna Lisa Suman, Silvia Migliorini, Fausto Corradeschi, Ilaria Ceccarelli, Annamaria Aloisi, and Giancarlo Carli ... patients exhibit lowered thresholds to experimentally induced mechanical, thermal and ischemic painful stimuli (Bennett 1999; Yunus 2001; Carli et ...