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Fukuko Kimura

Publications and source records attributed to Fukuko Kimura.

At least 19 recordsLinked to original sources
PubMed2006

Effects of neonatal testosterone treatment on sex differences in formalin-induced nociceptive behavior in rats.

There are sex differences in nociceptive behavior induced by formalin in rats. To determine whether these sex differences are the result of the sexual differentiation of the brain, that is masculinization and defeminization [A.P. Arnold, R.A. Gorski, Gonadal steroid induction of structural sex differences in the central nervous system, Annu. Rev. Neurosci. 7 (1984) 413-442; M.M. McCarthy, A.T.M. Konkle, When is a sex difference not a sex difference? Front Neuroendocrinol. 26 (2005) 85-102], some female rats were injected with testosterone propionate (TP, 100 microg/25 microl/rat) on the day of birth and on the following day. As controls, other female rats and all male rats were injected with the same volume of sesame oil. They were castrated at the age of 8 weeks, and implanted with a silicon tube containing 20% of 17beta-estradiol or cholesterol. Two weeks after the implantation, rats were injected with 50 microl of 2% formalin in the right hind paw and their behavioral changes were observed for 1h. In cholesterol-implanted rats, all rats exhibited three typical phases of pain response and there were no significant differences in the scores of nociceptive behavior. In 17beta-estradiol implanted rats, female and TP-treated female rats had a significantly higher score of nociceptive behavior than male rats. These results indicate that estrogen produces sex differences in nociceptive behavior induced by formalin, and suggest that these differences are not due to the sexual differentiation of the brain, since the dose and the timing of the TP treatment effectively defeminize and masculinize female rats. Alternatively, sexual differentiation of the brain response to formalin-induced nociceptive behavior may be different from ordinary sexual differentiation.

Analysis of Variance↗
PubMed2006

Bisphenol A induces transforming growth factor-beta3 mRNA in the preoptic area: a cDNA expression array and Northern blot study.

To gain better understanding of the effects of bisphenol A (BPA) in the adult brain, a cDNA expression array was used to screen possible candidates for BPA-inducible genes in the medial preoptic area (MPOA). Adult ovariectomized rats were given a subcutaneous injection of 10 mg BPA or sesame oil alone as a control. Twenty-four hours after the injection, the MPOAs were dissected and total RNAs were extracted. When expression levels of cDNAs derived from pooled samples were compared to controls, the expression levels of some genes in BPA-injected rats appeared to be different from those in sesame oil-injected rats. Among the candidate genes, we focused on an increase in the expression of transforming growth factor (TGF)-beta3 mRNA. To quantify the change in TGF-beta3 mRNA by BPA, we examined the effects of 10 mg BPA (n=6), 1 microg 17beta-estradiol (n=6), or oil injection (n=6) on the expression of TGF-beta3 mRNA in the MPOA of ovariectomized rats by Northern blot. The TGF-beta3 mRNA level in the MPOA of BPA-injected rats was significantly increased compared to the level in oil-injected rats (p<0.05). Injection of 1 microg 17beta-estradiol did not have any significant effect. The results suggest that, in the adult female rat, BPA acts on the MPOA by altering the expression of the TGF-beta3 gene in a manner distinct from that of estrogen.

Animals↗
PubMed2006

Effects of p-nonylphenol and 4-tert-octylphenol on the anterior pituitary functions in adult ovariectomized rats.

p-Nonylphenol (NP) and 4-tert-octylphenol (OP) are known to mimic the action of estrogens as endocrine disruptors. However, their acute effects on the pituitary and the hypothalamus functions in vivo have been uncertain. We therefore determined their effects on the anterior pituitary, in particular, gonadotropin secretion. Two weeks after ovariectomy, the rats were given a subcutaneous injection of 10 mg NP, 10 mg OP, 10 mg bisphenol A, 1 microg 17beta-estradiol, or sesame oil alone as control. Twenty-four hours after the treatment, the expression of progesterone receptor mRNA in the anterior pituitary and the level of luteinizing hormone (LH), follicle-stimulating hormone, and prolactin were determined. The expression of progesterone receptor mRNA in the anterior pituitary was significantly increased by either NP, OP, bisphenol A, or estradiol, but bisphenol A was less effective. The level of LH was significantly decreased by either NP or OP, but not by bisphenol A and estradiol. Only estradiol significantly increased the level of prolactin. The level of follicle-stimulating hormone was unchanged by any of the treatments. To check the effects of NP and OP on pulsatile LH secretion, blood samplings were done at 6-min intervals for 3 h. Twenty-four hours after treatment in ovariectomized adult rats, we found that the injection of NP significantly decreased the amplitude of LH pulses and the mean LH concentrations, but not the frequency of LH pulses. The injection of OP significantly decreased the mean LH concentrations without affecting the frequency and amplitude of the LH pulses. Finally, the rats given an injection of NP or sesame oil were intravenously injected with 50 ng of gonadotropin-releasing hormone (GnRH) to check whether NP affected the LH secretory responsiveness of the anterior pituitary to GnRH. We found that the responsiveness to GnRH in NP-injected rats was significantly attenuated compared to the sesame oil-injected rats. The present study suggests that NP, even with a single injection, suppresses the pulsatile LH secretion in adult ovariectomized rats, probably by affecting the anterior pituitary level.

Animals↗
PubMed2006

Sex differences in the basolateral amygdala: the extracellular levels of serotonin and dopamine, and their responses to restraint stress in rats.

The sex difference in the emotional response to stress suggests a sex-specific stress response in the amygdala. To examine the sex difference in extracellular levels of serotonin (5HT) and dopamine (DA) in the basolateral amygdala (BLA) and their responses to restraint stress, in vivo microdialysis studies were performed in male and female rats. In experiment I, dialysates were collected from the BLA at 15-min intervals under the freely moving condition. Mean extracellular levels of 5HT or DA in the BLA were higher in male rats than in female rats. In experiment II, rats were subjected to restraint stress for 60 min to examine the stress response of 5HT or DA levels. Although restraint stress significantly increased extracellular 5HT levels in both sexes of rats, female rats showed a greater response than male rats. Moreover, restraint stress significantly increased extracellular DA levels in female rats, but not in male rats. In experiment III, rats were subjected to restraint stress for 30 min to examine behavioral responses to restraint stress. Although no sex difference was observed in the number of audible vocalizations, male rats defecated a larger number of fecal pellets than female rats. In experiment IV, rats were tested for freezing behavior to examine contextual fear responses. Conditioned male rats showed a longer freezing time than conditioned female rats. We found sex differences in the extracellular levels of 5HT and DA in the BLA and their responses to restraint stress, which may be involved in the sex-specific emotional response to stress in rats.

Aggression↗
PubMed2005

Sex difference in the response of melanin-concentrating hormone neurons in the lateral hypothalamic area to glucose, as revealed by the expression of phosphorylated cyclic adenosine 3',5'-monophosphate response element-binding protein.

Because there are sex differences in feeding behavior in rats, we looked for a possible sex difference in the response to glucose of melanin-concentrating hormone (MCH) neurons in the lateral hypothalamic area using phosphorylated cAMP response element-binding protein (pCREB) as a marker of neural activity. Intact male rats and female rats at diestrus 2, proestrus, or estrus were fed normally or fasted for 48 h and injected with saline or glucose (400 mg/kg). Thereafter, preparations were subjected to immunohistochemical processing for the double staining of MCH and pCREB. Fasting increased the ratio of MCH neurons with pCREB (double-stained cells) in both male and female rats. In fasted rats, glucose injection decreased the ratio of double-stained cells more promptly in females than in males. The magnitude of decrease caused by glucose was greater at proestrus and estrus than at diestrus 2. Gonadectomy in males enhanced and in females attenuated the response of MCH neurons to glucose. Testosterone and estrogen replacement in males and females, respectively, restored the response of MCH neurons to glucose. The demonstrated sex differences in the response of MCH neurons to glucose correlated well with the gonadal steroid milieu; thus, MCH neurons may play an important role in sex differences in feeding behavior.

Animals↗
PubMed2005

Nicotine inhibits pulsatile luteinizing hormone secretion in human males but not in human females, and tolerance to this nicotine effect is lost within one week of quitting smoking.

CONTEXT AND OBJECTIVE: Despite having increased knowledge of the adverse reproductive effects of smoking, it is unclear whether nicotine affects the pulsatile LH secretion in humans. We addressed this issue in male and female smokers and nonsmokers. SUBJECTS AND METHODS: Twenty-nine male and 16 female nonsmokers and smokers were recruited as volunteers. In male smokers, nicotine effect was also studied before and after quitting smoking. In females, cyclic ovulatory function was assessed by measuring basal body temperature, and sampling studies were performed during the follicular phase. In the morning of the sampling day, an iv catheter was inserted into an anterobrachial vein, and blood samples (1.0-1.5 ml each) were taken at 10-min intervals for 480 min, during which, at 240 min, nicotine was administered via a transdermal patch (Nicotinell transdermal therapeutic system) containing 17.5 mg nicotine. Plasma LH was measured by immunoradiometric assay kits. RESULTS: Nicotine significantly lengthened the interpulse interval of pulsatile LH secretion in male nonsmokers but not in female nonsmokers. In male smokers, nicotine did not lengthen the interpulse interval, and in female smokers it was also ineffective. After quitting cigarette smoking in male smokers, the refractory to nicotine effect disappeared within 1 wk. CONCLUSIONS: We conclude that nicotine inhibits pulsatile LH secretion only in males, and the tolerance developed to the nicotine effect disappears within 1 wk of quitting cigarette smoking. However, we cannot deny the possibility that nicotine effect would have been detected in females if more subjects had been studied.

Drug Tolerance↗
PubMed2005

Feeding with powdered diet after weaning increases visuospatial ability in association with increases in the expression of N-methyl-D-aspartate receptors in the hippocampus of female rats.

We determined whether feeding with powdered diet improved the visuospatial ability in female rats by checking the expression of N-methyl-D-aspartate receptor (NMDAR) subunit 1 (NR1) mRNA in the hippocampus. In rats fed standard pelleted diet, males performed better than females in a radial 8-arm maze task as we reported previously. We found that the expression of NR1 mRNA, which may be the key mediator in visuospatial ability in the hippocampus, was also higher in males than in females. However, in rats fed powdered diet, no sex difference was seen in the radial 8-arm maze task and the expression of NR1 mRNA in the hippocampus, since feeding with powdered diet improved the visuospatial ability with increases in the expression of NR1 mRNA in the hippocampus in females. We suggest that the sex difference in visuospatial ability is at least in part due to feeding conditions.

Animals↗
PubMed2004

Intracerebroventricular injection of corticotropin-releasing hormone receptor antagonist blocks the suppression of pulsatile luteinizing hormone secretion induced by neuromedin U in ovariectomized rats after 48 hours of fasting.

We recently reported that neuromedin U (NMU) and fasting synergistically suppressed the pulsatile LH secretion, even though NMU has been shown to act as a satiety factor. In the present study, we examined whether this synergistic effect on the pulsatile LH secretion was mediated via corticotropin-releasing hormone (CRH) neurons. Adult ovariectomized (OVX) rats were stereotaxically implanted with a guide cannula into the third ventricle. After 2 weeks of recovery, blood samples were taken under freely-moving conditions at 6-min intervals for 180 min from 09:00 to 12:00 h in OVX rats that had been fasted for 48 h. After first 60 min of blood sampling, astressin (2 nmol/3 microl), a CRH receptor antagonist, dissolved in artificial cerebrospinal fluid (aCSF) or aCSF (3 microl) was injected as a control into the third ventricle. Thirty minutes after the first injection, the rats were injected with NMU (1 nmol/3 microl) into the third ventricle. We found that pre-treatment with astressin completely blocked the prolongation of the interpulse interval, which should be induced by NMU. We confirmed that a single intracerebroventricular injection of astressin per se did not affect the pulsatile LH secretion. The present study suggests that synergistic inhibitory effect of NMU and fasting on the pulsatile LH secretion is at least in part mediated via CRH neurons.

Analysis of Variance↗
PubMed2004

Female rats living in small cages respond to restraint stress with both adrenocortical corticosterone release and acetylcholine release in the hippocampus.

Since we found that the stress response of acetylcholine release in the hippocampus was attenuated in male rats living in a small cage, we individually housed female rats in a large (diameter=35 cm) or a small (19 cm) cylindrical cage for 4 days and examined the response to restraint stress which was applied from 12:00 h to 13:00 h. Both groups of rats showed a significant increase in the acetylcholine release in the hippocampus, as well as an increase in corticosterone release. But neither housing condition affected the expression of the 4-day estrous cycle. We surmise that there may be a sex difference in the effect of housing condition in the stress response of acetylcholine release in the hippocampus.

Acetylcholine↗
PubMed2004

Exposure to bisphenol A during gestation and lactation causes loss of sex difference in corticotropin-releasing hormone-immunoreactive neurons in the bed nucleus of the stria terminalis of rats.

It has been suspected that endocrine disrupters induce abnormal differentiation and development of reproductive organs. In the present study, we examined whether exposure to bisphenol A (BPA), a known endocrine disrupter, during gestation and lactation affects sex difference in the number of corticotropin-releasing hormone-immunoreactive neurons (CRH neurons) in the preoptic area (POA) and the bed nucleus of the stria terminalis (BST). For that purpose, pregnant female Wistar rats (n=8-11 per treatment group) were treated with either 0.1% ethanol (control group) or 10 mg/l BPA (BPA group) dissolved in their drinking water until their offspring were weaned. In the control group, we confirmed a previous report that the POA of female rats contained significantly more CRH neurons than that of male rats (p<0.05). This significant sex difference was also evident in the BPA group, indicating that BPA exposure used in the present study had no effect on the sex difference in CRH neurons in the POA. We also found in the control group that the BST of female rats contained significantly more CRH neurons (p<0.05) than that of male rats. However, this significant sex difference was not observed in the BPA group (p>0.05), suggesting that BPA exposure affected the sex difference in CRH neurons in the BST. Since there was no statistically significant difference in the number of CRH neurons between the control and the BPA group, irrespective of the sex, the results suggested that a loss of sex difference in CRH neurons was due to both an increase in CRH neurons in male rats and a decrease in CRH neurons in female rats. The present study indicates that there is a significant sex difference in the number of CRH neurons in the BST as well as in the POA and that exposure to BPA during gestation and lactation causes a loss of this sex difference in the rat BST, but not in the POA. We suggest that CRH neurons in the BST are more susceptible to endocrine disrupters than those in the POA, irrespective of the sex.

Animals↗
PubMed2004

Nicotine inhibition of pulsatile GnRH secretion is mediated by GABAA receptor system in the cultured rat embryonic olfactory placode.

In past work, we suggested that nicotine inhibition of in vivo pulsatile LH release is not mediated by opiate receptors known to be involved in the inhibition of LH release. In the present study, we examined whether nicotine inhibits the pulsatile gonadotropin-releasing hormone (GnRH) release, and whether this inhibition of GnRH release by nicotine is mediated by the GABA receptor system, by checking in vitro pulsatile GnRH release from cultured GnRH neurons obtained from olfactory placodes of rat embryos at E13.5. The mean interpulse interval of pulsatile GnRH release into the medium was 34.2+/-2.0 min in the control period and increased to 95.3+/-19.0 min (n=6) in the period of nicotine treatment at a concentration of 500 nM, showing an inhibitory effect of nicotine on pulsatile GnRH release. The GABA(A) receptor antagonist bicuculline used alone at a concentration of 20 microM caused no significant changes in the pulsatile GnRH release, but when used in combination with 500 nM of nicotine, bicuculline blocked the nicotine inhibition of GnRH release. In a separate experiment, nicotine treatment at a concentration of 500 nM significantly increased GABA release. These results suggest that, in the cultured embryonic olfactory placode, nicotine stimulates GABA release, which then inhibits GnRH release through GABA(A) receptor system.

Animals↗
PubMed2004

Effects of GABA and bicuculline on the electrical activity of rat olfactory placode neurons derived at E13.5 and cultured for 1 week on multi-electrode dishes.

The present study was performed to record the electrical activity of olfactory placode neurons and to check the effect of GABA and bicuculline on it. Olfactory placodes obtained at day 13.5 of gestation were cultured for 1 week on multi-electrode dishes. Olfactory placode neurons showed spontaneous firing, with firing rates of 0.77 +/- 0.05 Hz (0.03-3.82 Hz, n = 12), but there was no bursting activity. Perfusion with 10 microM GABA almost immediately inhibited 8 of 11 firing activities (we could not test it in 1 activity). In contrast, perfusion with 10 microM bicuculline induced facilitation in 5 of 12 activities and did not induce any change in 7 other activities. Statistical analysis by chi(2)-test showed a significant difference in the response of neurons to the two drugs. Fisher's exact probability test showed that the inhibitory effect of GABA was significant (p<0.05) whereas neither the facilitatory effect nor the lack of effect of bicuculline was significant (p>0.1). These results suggest that cultured olfactory placode neurons, even in a probably immature stage, respond to GABA with inhibition, as generally observed at mature stages.

Animals↗
PubMed2003

Effects of neuromedin U on the pulsatile LH secretion in ovariectomized rats in association with feeding conditions.

We examined the effects of intracerebroventricular injection of neuromedin U (NMU), at a dose that is reported to induce satiety in rats, on the pulsatile luteinizing hormone (LH) secretion in adult ovariectomized (OVX) rats under a normal feeding or a 48-h fasted condition. In OVX rats under the normal feeding condition, injection of NMU (1 nmol/3 microl) significantly decreased the mean LH concentration without affecting the frequency or amplitude of LH pulses, but under the 48-h fasted condition, it significantly decreased the mean LH concentration and the frequency of LH pulses without affecting the amplitude. The interpulse interval was significantly lengthened by NMU injection under the normal and the 48-h fasted condition, but the effect under the 48-h fasted condition was greater than under the normal feeding condition. We also confirmed that the 48-h fasted condition per se did not affect the pulsatile LH secretion in OVX rats. We suggest that NMU and fasting synergistically inhibit the pulsatile LH secretion, even though NMU has been said to act as a satiety factor.

Animal Feed↗
PubMed2003

Estrogen increases messenger RNA and immunoreactivity of aryl-hydrocarbon receptor nuclear translocator 2 in the rat mediobasal hypothalamus.

We examined the effect of estrogen on the expression of aryl-hydrocarbon receptor (AhR) and two types of AhR nuclear translocator (Arnt1 and Arnt2) mRNAs in the hypothalamus of ovariectomized rats. Northern blotting demonstrated that, in the mediobasal hypothalamus, a subcutaneous injection of 20 microg estradiol benzoate (E(2)) significantly increased the expression of Arnt2 mRNA, but induced no significant changes in the expression of AhR and Arnt1 mRNAs. The expression of Arnt2 mRNA was significantly increased at 4, 24, and 72h after the injection. Immunocytochemical study revealed that the number of Arnt2 immunoreactive cells was also significantly increased at 72h after the injection. Conversely, in the preoptic area, injection of E(2) did not cause significant changes in the expression of any of the three mRNAs. These observations suggest that estrogen regulates Arnt2 expression in the mediobasal hypothalamus and modulates the toxic action of dioxins in rats.

Animals↗
PubMed2003

Sexual dimorphism in the GABAergic control of gonadotropin release in intact rats.

GABA is a potent regulator of gonadotropin release both in male and female rats. We reported 24 h profiles of GABA release in the medial preoptic area (MPO) where gonadotropin-releasing hormone (GnRH) surge generator resides in female rats. In this article, we review the sex difference in 24 h profiles of GABA release. GABA release is high and episodic in male rats without any time dependency, but female rats showed a surge-like secretion of GABA in the early morning of the proestrous day. GABA release rapidly decreased until the afternoon of the day of proestrus followed by the preovulatory luteinizing hormone (LH) surge. The peak time of GABA episodes changes with estrous cycle in female rats. Fitting with the double cosinor method demonstrated that the acrophase of the GABA release in proestrous female rats occurs in the early morning, whereas the acrophases in diestrous females, estrous females and males occur at various time of day. Proestrous female rats showed significant difference in the peak time and acrophase of the GABA release compared with other estrous stages of female and male rats. These results demonstrated further sexual dimorphism of GABA release in the MPO, suggesting that coupling between the GABA release and the circadian clock may be a determining factor in the sex difference of the hypothalamo-pituitary-gonadal (HPG) axis in rats.

Animals↗
PubMed2003

Rats living in small cages respond to restraint stress with adrenocortical corticosterone release but not with hippocampal acetylcholine release.

We previously reported that the restriction of environmental space attenuated the hippocampal acetylcholine release and impaired spatial learning function. To examine the effect of the restriction of environmental space on the stress response of the hippocampal acetylcholine release, an in vivo microdialysis study was performed in male rats after 4 days of housing in a large cylindrical cage (diameter=35 cm) or a small cylindrical cage (diameter=19 cm). Significant stress response of the hippocampal acetylcholine release was observed in rats in the large cages (N=5), but it was not observed in rats in the small cages (N=5). The corticosterone concentration in serum was significantly increased by the restraint stress in both groups of rats. Although cage size does not influence stress-induced secretion of corticosterone, rats housed in a small cage exhibit lower levels of stress-induced ACh release than rats living in a large cage.

Acetylcholine↗