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ABSTRACT: To elucidate the effects of hyperpolarization-activated current If on robustness of sinoatrial node (SAN) pacemaking in connection with intracellular Na(+) concentration (Nai) changes, we theoretically investigated 1) the impacts of If on dynamical properties of central SAN model cells during inhibition of L-type Ca(2+) channel currents (ICaL) or hyperpolarizing loads, and 2) If-dependent changes in Nai and their effects on dynamical properties of model cells. Bifurcation analyses were performed for Nai-variable and Nai-fixed versions of mathematical models for rabbit SAN cells; equilibrium points (EPs), limit cycles (LCs), and their stability were determined as functions of model parameters. Increasing If conductance (gf) shrank ICaL conductance (gCaL) region of unstable EPs and stable LCs (rhythmic firings) in the Nai-variable system, while slightly broadening that of rhythmic firings at lower gf in the Nai-fixed system. In the Nai-variable system, increased gf yielded elevations in Nai at EPs and during spontaneous oscillations, which caused EP stabilization and shrinkage in the parameter regions of unstable EPs and rhythmic firings. As gf increased, parameter regions of unstable EPs and stable LCs determined for hyperpolarizing loads shrank in the Nai-variable system, while enlarging in the Nai-fixed system. These findings suggest that 1) If does not enhance but attenuates robustness of rabbit SAN cells via facilitating EP stabilization and LC destabilization even in physiological gf ranges, and 2) the enhancing effect of If on robustness of pacemaker activity, which could be observed at lower gf when Nai was fixed, is actually reversed by If-dependent changes in Nai.
AJP Heart and Circulatory Physiology 03/2013; · 3.71 Impact Factor
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ABSTRACT: We previously demonstrated that the peptidergic neurotransmitter pituitary adenylate cyclase-activating polypeptide (PACAP) affects autonomic system and contributes to the control of metabolic and cardiovascular functions. Previous studies have demonstrated the importance of centrally-mediated sympathetic effects of leptin for obesity-related hypertension. Here we tested whether PACAP signaling in the brain is implicated in leptin-induced sympathetic excitation and appetite suppression. In anesthetized mice, intracerebroventricular (ICV) pre-treatment with PACAP6-38, an antagonist of the PACAP receptors (PAC1-R and VPAC2), inhibited the increase in white adipose tissue sympathetic nerve activity (WAT-SNA) produced by ICV leptin (2 μg). In contrast, leptin-induced stimulation of renal sympathetic nerve activity (RSNA) was not affected by ICV pre-treatment with PACAP6-38. Moreover, in PACAP-deficient (Adcyap1-/-) mice, ICV leptin-induced WAT-SNA increase was impaired, whereas RSNA response was preserved. The reduction in food intake and body weight evoked by ICV leptin were attenuated in Adcyap1-/- mice. Our data suggests that hypothalamic PACAP signaling play a key role in the control by leptin of feeding behavior and lipocatabolic sympathetic outflow, but spares the renal sympathetic traffic.
Neuroscience 02/2013; · 3.38 Impact Factor
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Mamoru Tanida,
Atsuko Hayata,
Norihito Shintani,
Naoki Yamamoto,
Yasutaka Kurata,
Toshishige Shibamoto,
Donald A Morgan,
Kamal Rahmouni,
Hitoshi Hashimoto,
M Tanida,
A Hayata,
N Shintani,
N Yamamoto,
Y Kurata,
T Shibamoto,
D A Morgan,
K Rahmouni,
H Hashimoto
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ABSTRACT: Central PACAP mediates the sympathetic effects of leptin in a tissue-specific manner, Neuroscience (2013), doi: http://dx.doi.org/10.1016/j.neuroscience.2013.02.016 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Neuroscience 02/2013; · 3.38 Impact Factor
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ABSTRACT: Intestinal administration of various lactobacilli has been reported to affect autonomic neurotransmission, blood pressure, and body weight in rats. In this study, we isolated 3 molecules (Peaks A, B, C) from the Lactobacillus pentosus strain S-PT84 (S-PT 84) culture supernatants. Intraduodenal (ID) injection of these molecules increased or inhibited renal sympathetic nerve activity (RSNA) in rats as follows: Peak A: 134%, Peak B: 40.1%, Peak C: 408%. Furthermore, we identified Peak C as 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one (DDMP). ID injection of DDMP increased brown adipose tissue sympathetic nerve activity (BAT-SNA; 118% ± 15.3%), while intra-oral injection of DDMP increased the body temperature above the interscapular brown adipose tissue (BAT-T; 0.72 ± 0.13°C) in rats. These data suggest that S-PT84 produces molecules that modulate autonomic nerve activity. In addition, DDMP increased BAT-SNA and BAT-T, and these changes in BAT-T may be caused by changes in BAT-SNA.
Journal of Agricultural and Food Chemistry 10/2012; · 2.82 Impact Factor
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ABSTRACT: L-carnosine (β-alanyl-L-histidine; CAR) is synthesized in mammalian skeletal muscle. Although the physiological roles of CAR have not yet been clarified, there is evidence that the release of CAR from skeletal muscle during physical exercise affects autonomic neurotransmission and physiological functions. In particular, CAR affects the activity of sympathetic and parasympathetic nerves innervating the adrenal glands, liver, kidney, pancreas, stomach, and white and brown adipose tissues, thereby causing changes in blood pressure, blood glucose, appetite, lipolysis, and thermogenesis. CAR-mediated changes in neurotransmission and physiological functions were eliminated by histamine H1 or H3 receptor antagonists (diphenhydramine or thioperamide) and bilateral lesions of the hypothalamic suprachiasmatic nucleus (SCN), a master circadian clock. Moreover, a carnosine-degrading enzyme (carnosinase 2) was shown to be localized to histamine neurons in the hypothalamic tuberomammillary nucleus (TMN). Thus, CAR released from skeletal muscle during exercise may be transported into TMN-histamine neurons and hydrolyzed. The resulting L-histidine may subsequently be converted into histamine, which could be responsible for the effects of CAR on neurotransmission and physiological function. Thus, CAR appears to influence hypoglycemic, hypotensive, and lipolytic activity through regulation of autonomic nerves and with the involvement of the SCN and histamine. These findings are reviewed and discussed in the context of other recent reports, including those on carnosine synthetases, carnosinases, and carnosine transport.
Amino Acids 02/2012; 43(1):97-109. · 3.25 Impact Factor
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ABSTRACT: In this study, we examined the effect of intracerebroventricular (ICV) injection of 5-aminoimidazole-4-carboxamide 1-beta-d-ribofuranoside (AICAR), an AMP-activated protein kinase (AMPK) activator, or compound C (CC), an AMPK inhibitor, on the activity of sympathetic nerves innervating the adrenal gland and kidney in urethane-anesthetized rats to elucidate the role of AMPK in sympathetic nervous system function. We found that an ICV injection of AICAR or CC significantly stimulated renal sympathetic nerve activity (RSNA) and adrenal sympathetic nerve activity (ASNA) in a dose-dependent manner. Following this, we examined the role of AMPK on the sympatho-excitation caused by leptin injection. Pretreatment with AICAR or CC eliminated the leptin-induced increase in RSNA, however, neither pretreatment with AICAR or CC affected the leptin-induced increase in ASNA. Our data suggest that AMPK may regulate the sympathetic nerve system, and that the stimulating effect of leptin on sympathetic nerve activity in kidney may depend on central AMPK.
Neuroscience Letters 08/2011; 503(3):167-70. · 2.11 Impact Factor
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ABSTRACT: Earlier examination reported that central injection of nesfatin-1 elevated blood pressure and suppressed food intake in conscious rats. In this study, we analyzed the effects of the intracerebroventricular injection of nesfatin-1 on the sympathetic nerve outflow to the kidney in urethane-anesthetized rats. An intracerebroventricular injection of nesfatin-1 significantly stimulated renal sympathetic nerve activity and blood pressure in a dose-dependent manner. Moreover, we examined the role of the melanocortin system on the sympathoexcitation caused by the nesfatin-1 injection. Pretreatment with the melanocortin-3/4 receptor antagonist, SHU9119, abolished the increase in nerve activity and blood pressure induced by nesfatin-1. Thus, the stimulating effects of nesfatin-1 administration on the sympathetic nerve activity of the kidney may depend on the central melanocortin system.
Neuroreport 04/2011; 22(6):309-12. · 1.66 Impact Factor
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ABSTRACT: Lentinus edodes, known as shiitake mushroom in Japan and Xiang Gu or fragrant mushroom in China, is an edible mushroom that is commonly cultivated
worldwide. This mushroom has been consumed for centuries as a delicacy and for its beneficial effects on human health. Early
in the fourteenth century, the Chinese physician Wu Rui recorded that shiitake was beneficial for the treatment of various
forms of malignancy. Since 1969, groundbreaking investigations have performed in this subject, and a large number of high
quality scientific studies have demonstrated the immunomodulatory, antitumor, antiviral, and cholesterol-regulating effects
of this mushroom. In addition, the use of shiitake in combination with chemotherapy and radiotherapy has reported in Japan.
Since cancer is a leading cause of death worldwide and it is exceptionally difficult to cure malignant tumors, cancer prevention
may be a more effective strategy to control and ultimately overcome cancer. Here, we will summarize the antitumor activity
and immunomodulating action of biologically active polysaccharides, mostly β-glucans, from shiitake mushroom fruit bodies
and/or cultured mycelium based on experimental and clinical findings. The following aspects of shiitake mushroom in relation
to cancer would be discussed: mechanisms of action, optimal dosage, and timing of administration for clinical use of its antitumor
and immunostimulating properties, prospective use in clinical therapy, clinical safety, and possible adverse effects.
03/2011: pages 303-317;
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Naohiro Tsukiyama,
Yoko Saida,
Michiya Kakuda,
Norihito Shintani,
Atsuko Hayata,
Yoshiko Morita, Mamoru Tanida,
Minako Tajiri,
Keisuke Hazama,
Katsuya Ogata,
Hitoshi Hashimoto,
Akemichi Baba
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ABSTRACT: Pituitary adenylate cyclase-activating polypeptide (PACAP) is a pleiotropic neuropeptide widely distributed in the nervous system. Recently, PACAP was shown to be involved in restraint stress-induced corticosterone release and concomitant expression of the genes involved in hypothalamic-pituitary-adrenal (HPA) axis activation. Therefore, in this study, we have addressed the types of stressors and the levels of the HPA axis in which PACAP signaling is involved using mice lacking PACAP (PACAP⁻/⁻). Among four different types of stressors, open-field exposure, cold exposure, ether inhalation, and restraint, the corticosterone response to open-field exposure and restraint, which are categorized as emotional stressors, but not the other two, was markedly attenuated in PACAP⁻/⁻ mice. Peripheral administration of corticotropin releasing factor (CRF) or adrenocorticotropic hormone induced corticosterone increase similarly in PACAP⁻/⁻ and wild-type mice. In addition, the restraint stress-induced c-Fos expression was significantly decreased in the paraventricular nucleus (PVN) and medial amygdala (MeA), but not the medial prefrontal cortex, in PACAP⁻/⁻ mice. In the PVN of PACAP⁻/⁻ mice, the stress-induced c-Fos expression was blunted in the CRF neurons. These results suggest that PACAP is critically involved in activation of the MeA and PVN CRF neurons to centrally regulate the HPA axis response to emotional stressors.
Stress (Amsterdam, Netherlands) 03/2011; 14(4):368-75. · 3.21 Impact Factor
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ABSTRACT: Niijima previously reported that intragastric infusion of glutamate has increased the activity of the efferent parasympathetic nerves that innervate the stomach and pancreas in urethane-anesthetized rats. In the present study, the effects of intragastric injection of glutamate on the efferent sympathetic nerve outflow to the kidney and the white adipose tissue in rats were analyzed. Although the sympathetic nerve activities of the renal and white adipose tissues were not affected after intragastric glutamate injection in rats that were fasted for 3h, these activities were significantly accelerated after intragastric glutamate injection in rats that were fasted for 48h. Moreover, to test the role of the afferent neural pathway on sympathoexcitation caused by glutamate injection, the effects of vagotomy, or sympathetic denervation, were also examined. In vagotomized rats, the sympathetic nerve activities of the renal and white adipose tissues were eliminated after glutamate injection, but these activities remained unaffected in rats that underwent sympathetic denervation. Thus, the stimulating effects of glutamate administration on the sympathetic nerve activities of the renal and white adipose tissues could depend on the length of the fast and the vagal afferent pathway.
Neuroscience Letters 03/2011; 491(3):211-5. · 2.11 Impact Factor
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ABSTRACT: Pituitary adenylate cyclase-activating polypeptide (PACAP) is a peptidergic neurotransmitter that is highly expressed in the nervous system. We have previously reported that a central injection of PACAP leads to changes in the autonomic nervous system tones including sympathetic excitation and parasympathetic inhibition. An anatomical study revealed that melanocortin and PACAP are colocalized in some hypothalamic nuclei. Here, we investigated the possible role of the melanocortin system in autonomic control by PACAP using SHU9119, an antagonist of the melanocortin receptors (MC3-R/MC4-R). Pretreatment with SHU-9119 did not affect the activating neural responses of adrenal, renal, and lumbar sympathetic nerves following a PACAP injection However, SHU9119 significantly eliminated the suppressing effect of a PACAP injection on gastric vagal nerve activity and excitation effects on liver and brown adipose tissue sympathetic nerve activities. These results suggest that the brain melanocortin system might play a key role in the control of thermogenic sympathetic outflows and digestive parasympathetic outflow by PACAP, but this system does not participate in the central effects of PACAP on cardiovascular function and neural activities of renal, adrenal, and lumbar sympathetic nerves.
Neuroscience Research 02/2011; 70(1):55-61. · 2.25 Impact Factor
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ABSTRACT: Pituitary adenylate cyclase-activating polypeptide (PACAP) is a highly conserved pleiotropic neuropeptide that functions as a neurotransmitter, neuromodulator and neurotrophic factor. Accumulating evidence implicates PACAP as an important regulator of both central and/or peripheral components of the stress axes, particularly exposure to prolonged or traumatic stress. Indeed, PACAP and its cognate receptors are widely expressed in the brain regions and peripheral tissues that mediate stress-related responses. In the sympathoadrenomedullary system, PACAP is required for sustained epinephrine secretion during metabolic stress. It is likely that PACAP regulates autonomic function and contributes to peripheral homeostasis by maintaining a balance between sympathetic and parasympathetic activity, favoring stimulation of the sympathetic system. Furthermore, PACAP is thought to act centrally on the paraventricular nucleus of the hypothalamus to regulate both the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. Intriguingly, PACAP is also active in brain structures that mediate anxiety- and fear-related behaviors, and the expression of PACAP and its receptors are dynamically altered under pathologic conditions. Thus PACAP may influence both hard-wired (genetically determined) stress responses and gene-environment interactions in stress-related psychopathology. This article aims to overview the molecular mechanisms and psychiatric implications of PACAP-dependent stress responses.
Current pharmaceutical design 01/2011; 17(10):985-9. · 4.41 Impact Factor
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ABSTRACT: Eucommia ulmoides Oliver leaf extracts (ELE) have been shown to exert a hypolipidemic effect in hamsters. Therefore, it was hypothesized that ELE might affect lipid metabolism via changes in autonomic nerve activities and causes changes in thermogenesis and body weight. We examined this hypothesis, and found that intraduodenal (ID) injection of ELE elevated epididymal white adipose tissue sympathetic nerve activity (WAT-SNA) and interscapular brown adipose tissue sympathetic nerve activity (BAT-SNA) in urethane-anesthetized rats and elevated the plasma concentration of free fatty acids (FFA) (a marker of lipolysis) and body temperature (BT) (a marker of thermogenesis) in conscious rats. Furthermore, it was observed that ID administration of ELE decreased gastric vagal nerve activity (GVNA) in urethane-anesthetized rats, and that ELE given as food reduced food intake, body and abdominal adipose tissue weights and decreased plasma triglyceride level. These findings suggest that ELE stimulates lipolysis and thermogenesis through elevations in WAT-SNA and BAT-SNA, respectively, suppresses appetite by inhibiting the activities of the parasympathetic nerves innervating the gastrointestinal tract, including GVNA, and decreases the amount of abdominal fat and body weight via these changes.
Neuroscience Letters 08/2010; 479(3):181-6. · 2.11 Impact Factor
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ABSTRACT: We observed that olfactory stimulation with scent of grapefruit oil elevated the activities of sympathetic nerves, and increased the plasma glycerol concentration and blood pressure. In contrast, olfactory stimulation with scent of lavender oil had opposite effects in rats. These suggest that changes in autonomic activities cause physiological functions via histaminergic H1 and H3 receptor. Moreover, it has been reported that somatic sensory stimulation affected autonomic neurotransmission. To examine effects of skin application of urea-containing cream on cutaneous arterial sympathetic nerve activity (CASNA), blood flow, and transepidermal water loss (TEWL).
The activity of CASNA was determined by electrophysiological method, and cutaneous blood flow was determined using laser flowmeter in urethane-anesthetized rats, TEWL was measured using VapoMeter in the back skin of HWY hairless rats.
CASNA was markedly and significantly inhibited by skin application of 10% urea-containing cream, whereas cutaneous blood flow was significantly elevated via histaminergic H3-receptor. In conscious hairless rats, TEWL was significantly decreased 24 h after application of 10% urea-containing cream to the back skin.
These findings suggest that skin application of 10% urea-containing cream increases the cutaneous blood flow and water retaining ability, and that histaminergic H3-receptors may mediate these effects.
Skin Research and Technology 08/2010; 17(1):75-81. · 1.71 Impact Factor
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ABSTRACT: Nutrient information from the gastrointestinal tract to the brain plays a critical role in the regulation of appetite and energy homeostasis. The autonomic nervous system controls the functions of several tissues to regulate the energy homeostasis of the whole body. Autonomic nerve activity is influenced by environmental or exogenous changes in even a single tissue. In the present study, we investigated the effect of an intraduodenal injection of fat on the activities of the autonomic nerves innervating the adrenal gland and stomach in urethane-anesthetized rats. An intraduodenal injection of corn oil suppressed adrenal efferent sympathetic nerve activity (ASNA) and stimulated gastric efferent vagal nerve activity (GVNA). A lipase inhibitor, epsilon-polylysine, coinjected with corn oil completely suppressed the corn oil-induced changes in ASNA and GVNA. Further, an intraduodenal injection of fatty acid (linoleic acid) moderately suppressed ASNA and significantly stimulated GVNA; these results indicate that fat may affect autonomic nerve activity partly through the chemoreception of free fatty acids (FFAs), which are produced during the hydrolysis of fat (corn oil) by a pancreatic lipase, in the intestinal lumen. Furthermore, an intraduodenal injection of an intravenous fat emulsion with the same pH and osmotic pressure as the body fluid affected ASNA and GVNA in a similar manner as corn oil. These results suggest that intraduodenal fat suppresses ASNA and stimulates GVNA partly via the chemoreception of FFAs-the degradation products of fats-in the intestinal lumen.
Neuroscience Research 03/2010; 67(3):236-44. · 2.25 Impact Factor
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ABSTRACT: Pituitary adenylate cyclase-activating polypeptide (PACAP) is a peptidergic neurotransmitter that is expressed in high levels in nervous systems. Here, we investigated the roles of PACAP in autonomic system regulation by evaluating the changes caused in the autonomic nerve activities after injecting PACAP into the central nervous system (CNS) and examining stress-induced blood glucose changes in PACAP-deficient (PACAP-/-) mice. Renal sympathetic nerve activity (RSNA), blood pressure, and heart rate were elevated after injecting PACAP into the third cerebral ventricle (3CV). Similarly, other sympathetic nerve activities, including adrenal sympathetic nerve activity (ASNA), celiac sympathetic nerve activity (CSNA), and brown adipose tissue sympathetic nerve activity (BAT-SNA), were accelerated by PACAP injection. In contrast, injecting PACAP into 3CV significantly suppressed parasympathetic nerve activities, including gastric vagal nerve activity (GVNA) and celiac vagal nerve activity (CVNA). In addition, blood glucose elevations induced by stress, such as immobilization or ether exposure, were disrupted in PACAP-/- mice, although basal glucose levels in mutants were comparable to that in wild-type mice. These results suggest that CNS PACAP regulates autonomic function by maintaining a sympathetic-parasympathetic balance and contributes to peripheral homeostatic maintenance, especially under conditions of stress.
Regulatory Peptides 02/2010; 161(1-3):73-80. · 2.11 Impact Factor
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ABSTRACT: In a previous report, evidence was presented that flavangenol supplementation has an anti-ischemic effects in rats. In the study presented here, we examined the autonomic effects of intraduodenal (ID) injection of flavangenol in urethane-anesthetized rats and found that it increased sympathetic nerve activity innervating brown adipose tissue (BAT-SNA) in a dose-dependent manner, while it suppressed gastric vagal nerve activity (GVNA). In addition, intra-oral (IO) injection of flavangenol elevated brown adipose tissue temperature (BAT-T). Furthermore, flavangenol drinking for 15 d reduced body weight gain in rats fed a high-fat diet. These results thus suggest that flavangenol supplementation exerts its reducing action on body weight through changes in autonomic neurotransmission.
Bioscience Biotechnology and Biochemistry 11/2009; 73(11):2374-8. · 1.28 Impact Factor
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ABSTRACT: Changes in the activity of the autonomic nervous system are good indicators of alterations in physiological phenomena such as the body temperature, blood glucose, blood pressure. Hesperidin, a flavanone known as vitamin P, has been shown to reduce the levels of serum lipids, cholesterol, and blood pressure. However, hesperidin is not water-soluble and is not well absorbed from the intestine. G-hesperidin (4G-alpha-glucopyranosyl hesperidin) is more water-soluble and more rapidly absorbed than hesperidin. In order to clarify the functions of G-hesperidin, we examined the effects of oral administration of G-hesperidin on interscapular brown adipose tissue-sympathetic nerve activity (BAT-SNA) and cutaneous sympathetic nerve activity (CASNA) in rats weighing about 300 g. In this study, we found that oral administration of 60 mg of G-hesperidin increased the BAT-SNA but decreased the CASNA in urethane-anesthetized rats. Since an elevation in BAT-SNA increases heat production (i.e. body temperature (BT)) and a decrease in CASNA increases cutaneous perfusion, we examined whether oral administration of G-hesperidin had an effect on the peripheral BT in rats. Consequently, we observed that the subcutaneous BT at the caudal end of the back after oral administration of 60 mg of G-hesperidin was significantly higher than the subcutaneous BT after oral administration of water in conscious rats. These findings suggest that G-hesperidin enhances the BAT-SNA and suppresses the CASNA resulting in an increase in the peripheral BT, probably by an increase in the thermogenesis in the BAT and an elevation in the cutaneous blood flow.
Neuroscience Letters 07/2009; 461(1):30-5. · 2.11 Impact Factor
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Hitoshi Hashimoto,
Ryota Hashimoto,
Norihito Shintani,
Kazuhiro Tanaka,
Akiko Yamamoto,
Michiyoshi Hatanaka,
Xiaohong Guo,
Yoshiko Morita, Mamoru Tanida,
Katsuya Nagai,
Masatoshi Takeda,
Akemichi Baba
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ABSTRACT: Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide with pleiotropic functions. We report here that PACAP-deficient (PACAP-/-) mice showed increased immobility in a forced swimming test, which was reduced by the antidepressant desipramine, to a similar extent as in wild-type mice. The atypical antipsychotic risperidone and the selective serotonin (5-HT)(2) antagonist ritanserin normalized the depression-like behavior in PACAP-/- mice. The 5-HT(2) agonist (+/-)-2,5-dimethoxy-4-iodoamphetamine-induced 5-HT syndrome was exaggerated in PACAP-/- mice, which suggests a 5-HT(2)-receptor-dependent mechanism in the depression-like behavior. The circadian rhythm of plasma corticosterone and body core temperature was significantly flattened in the mutants. mRNA expression of glucocorticoid receptor was reduced in the mutant hippocampus. The present results suggest that alterations in PACAP signaling might contribute to the pathogenesis of certain depressive conditions amenable to atypical antipsychotic drugs.
Journal of Neurochemistry 06/2009; 110(2):595-602. · 4.06 Impact Factor
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ABSTRACT: The spleen is an important organ for tumor immunity, and the splenic sympathetic nerve has a suppressive effect on splenic natural killer (NK) cytotoxicity. On the basis of this and reports that Lentinus edodes (Shiitake mushroom) has tumor-inhibitory effects, the authors hypothesized that an extract of a mycelial culture of L. edodes grown in a solid medium of sugar-cane bagasse and defatted rice bran-L.E.M-might affect the sympathetic splenic sympathetic nerve activity (Splenic-SNA) and thus inhibit tumor proliferation. Thus, the effect of L.E.M on Splenic-SNA and human cancer cell proliferation was examined. Splenic-SNA was found to be suppressed by an intraduodenal L.E.M injection in urethane-anesthetized rats, which significantly inhibited increases in the tumor volume of human colon and breast cancer cells implanted in athymic nude mice. These findings suggest that L.E.M has an inhibitory effect on tumor proliferation possibly via a reduction in NK cytotoxicity through the suppression of Splenic-SNA.
Autonomic neuroscience: basic & clinical 01/2009; 145(1-2):50-4. · 1.82 Impact Factor
