Role of peripheral catecholamine mechanisms in central activation of the hypophyseo-adrenocortical system induced by reserpine

Inhibition of the function of the peripheral divisions of the sympathico-adrenal system prevents the manifestations of stimulation of the hypophyseo-adrenocortical system by the action of reserpine.Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 70, No. 12, pp. 51–54, December, 1970.     

Role of gamma-aminobutyric acid in the activation of the pituitary-testicular complex of mice induced by the presence of a female

Conclusions Thus, the accumulation of GABA in the organism after the administration of an inhibitor of -ketoglutatrate-GABA transaminase blocks the rise in the testosterone level in the peripheral blood plasma of male mice induced by the presence of a receptive female. The inhibiting effect of the blocker of GABA metabolism depends on the genotype of the animal. When a, receptive female is encountered under normal conditions, the inhibiting effect of GABA is not manifested, since neither blockage of the GABA receptors by bicuculline nor a decrease in its content in the organism after the administration of the glutamate decarboxylase inhibitor TSC has any effect on the rise in the testosterone level in the blood during sexual excitation.It has been suggested that the GABAergic mechanism inhibits sexual excitation of the male when he encounters a receptive female only under conditions of stress.Translated from Problemy Éndokrinologii, Vol. 33, No. 4, pp. 48–51, July–August, 1987.     

Sirt1参与异丙肾上腺素诱导的小鼠心肌肥大

目的:观察Ⅲ类组蛋白去乙酰基酶1(Sirt1)在异丙肾上腺素(ISO)诱导的小鼠心肌肥大中的表达及作用。方法:昆明小鼠随机分为正常对照组、ISO模型组和ISO+NAM(烟酰胺,Sirt1抑制剂)组。皮下注射ISO诱导小鼠心肌肥大。以心脏重量指数(心脏重量/体重)、HE染色、透射电镜以及脑钠肽(BNP)mRNA表达水平观察心肌肥大的变化。同时采用RT-PCR、Western blotting检测各组心肌Sirt1 mRNA、蛋白质的表达。结果:与对照组相比,心脏重量指数,HE染色,透射电镜以及BNP mRNA表达水平均显示皮下注射ISO可明显诱导小鼠心肌肥大;Sirt1在心肌肥大模型组表达显著增多(P0.01),其抑制剂NAM可明显减轻ISO诱导的心肌肥大(P0.05),并降低Sirt1的表达(P0.01)。结论:Sirt1的激活可能参与ISO诱导的小鼠心肌肥大。     

高浓度骨桥蛋白诱导双足直立雌性小鼠脊柱侧凸模型

BACKGROUND: In recent years, the relevant research confirmed that increased levels of osteopontin may lead to the development of adolescent idiopathic scoliosis. The establishment of appropriate animal models of adolescent idiopathic scoliosis is of great significance in the research and treatment of such diseases. OBJECTIVE: To observe the occurrence of scoliosis of the bipedal female mice induced by high concentration of osteopontin, and provide evidence for establishing ideal drug models of adolescent idiopathic scoliosis. METHODS: C3H/HeJ mice of the same age were selected and randomly assigned to high-concentration osteopontin female mice (n=20) and male mice (n=20). This study also set control male mice group (n=20) and control female mice group (n=20). Mice aged 3 weeks from four groups were subjected to upper limb amputation and rat tail resection to establish bipedal mouse models. After surgery, a special cage was used to induce the upright state. High-concentration osteopontin female mice and male mice were daily intraperitoneally injected with high-concentration osteopontin (40 μg/kg). Mice in the control group were intraperitoneally injected with physiological saline. At 3 months after induction, animal spine X-ray examination was conducted to measure Cobb angle. If Cobb angle was greater than 10°, a successful induction was set. The incidence and severity of scoliosis were evaluated. RESULTS AND CONCLUSION: (1) In the high-concentration osteopontin female mice group, scoliosis was observed in 18 mice. Cobb angle was 16°-38°, averagely (25.8±6.7)°. In the high-concentration osteopontin male mice group, scoliosis was observed in 16 mice. Cobb angle was 11°-34°, averagely (20.9±6.8)°. In the control male mice group, scoliosis was observed in 8 mice. Cobb angle was 12°-21°, averagely (15.6±3.1)°. In the control female mice group, scoliosis was observed in 9 mice. Cobb angle was 11°-24°, averagely (17.1±4.5)°. (2) The incidence of scoliosis was significantly higher in the high-concentration osteopontin female and male mice groups than in the control female and male mice groups (P < 0.05). No significant difference in the incidence of scoliosis was detected between high-concentration osteopontin female and male mice groups (P > 0.05). However, curve magnitude was significantly severer in the high-concentration osteopontin female mice group than in the high-concentration osteopontin male mice group (P < 0.05). (3) Results suggested that the scoliosis incidence was higher and scoliosis was severer in high-concentration osteopontin-induced bipedal mice, which was more closed to human. 中国组织工程研究杂志出版内容重点：肾移植;肝移植;移植;心脏移植;组织移植;皮肤移植;皮瓣移植;血管移植;器官移植;组织工程     

Clip induced analgesia and immobility in the mouse: activation by different sensory modalities

In the present study we have attempted to characterize, in mice, a situation which appears to simulate real life predation and elicits simultaneous analgesia and immobility. We utilized pinch produced by clip application to various regions of the body and examined its effect on responsiveness to noxious stimuli and motor behavior. Intense noxious clip was applied to the nape of the neck, back and base of the tail. The area most effective for the elicitation of both clip induced analgesia and immobility was the nape of the neck while tail pinch resulted in analgesia but not immobility. Evidence is provided that different systems are responsible for clip induced immobility and analgesia. Temporal dissociation of clip induced analgesia and immobility could be demonstrated with continuous clip application for 30 min showing a different time course for the analgesic and immobilizing effects. Different stimuli were effective in eliciting clip induced analgesia and immobility with noxious stimuli essential for the induction of clip induced analgesia and innocuous stimuli sufficient for clip induced immobility. Thus, low analgesic doses of local anesthetics injected into the nape of the neck prevented noxious clip from inducing analgesia but immobility was still evident. In contrast, nonnoxious pinch to the nape of the neck elicited immobility but not analgesia and clip induced immobility could still be induced after the administration of high doses of morphine which completely blocked responses to noxious stimuli. These results demonstrate that in a situation resembling natural predation both analgesia and immobility are produced concurrently but that these behavioral phenomena can be elicited differentially and may be mediated by different independent systems.     

Involvement of major histocompatibility complex class I antigens in T cell activation

During the last few years ample evidence has been collected indicating a regulatory role for major histocompatibility complex class I antigens (Ag) in T cell activation. However, due to differential effects (stimulatory and inhibitory) of anti-class I antibodies (Ab) observed under different conditions, no coherent scheme of the mechanism of action of these Ag has emerged. Here, we present evidence that the mode of action of anti-class I Ab depends upon the presence or absence of monocytes/macrophages (M phi) in the culture. The Ab inhibit Ag presentation by binding to M phi. Coating of tetanus toxin -pulsed M phi with anti-class I Ab is sufficient to suppress T cell activation. On the contrary, these Ab enhance lectin- as well as phorbol ester-induced T cell activation in the absence of M phi. Cross-linking of class I Ag on T cell surface mobilizes cytoplasmic Ca2+, and also enhances the CD3-induced Ca2+ flux inside the cells indicating a functional relationship between CD3 and class I Ag. Though surface modulation and immunoprecipitation experiments do not indicate any physical association between these two types of molecules on the T cell surface, capping studies show that cross-linking of class I Ag induces an association of these Ag with CD3. Binding of anti-CD3 Ab enhances the strength of association between CD3 and class I Ag, and the former co-caps completely with the latter. Based on these observations we propose that during antigen presentation M phi (or Ag-presenting cells) and T cells, besides interacting via peptide--class II Ag/CD3--T cell receptor complex formation, also interact through class I Ag. The latter interaction may stabilize the contact formation between T cells and Ag-presenting cell and support T cell activation.     

Neutrophil erythrotoxicity induced by phorbol myristate acetate: mechanisms involved in neutrophil activation

The capacity of phorbol myristate acetate (PMA) to prime neutrophil cytotoxic responses induced by a second stimulus was investigated. Treatment of neutrophils with low concentrations of PMA (0.2-0.5 ng/ml) for 18 hr at 37 degrees C markedly enhanced cytotoxicity triggered by Ca2+ ionophore A23187, N-formyl-methionyl-leucyl-phenylalanine (FMLP) and PMA. Pretreatment with PMA also enabled neutrophils to mediate significant cytotoxicity when triggered by platelet-activating factor (PAF), a stimulus unable to induce untreated cells to display cytotoxicity. Conversely, neutrophil cytotoxicity triggered by immune complexes (IC) was not modified by PMA treatment, whereas cytolytic activity of neutrophils against antibody-sensitized target cells was significantly increased. Treatment with PMA concentrations higher than 1 ng/ml directly triggered neutrophil cytotoxicity. Interestingly, we found that PMA-triggered neutrophils were able to sustain maximal levels of cytotoxicity for at least 8 hr after stimulation. With regard to the mechanisms involved in neutrophil activation by PMA, we found that catalase but not superoxide dismutase (SOD) prevented neutrophil activation measured as 1) induction of cytotoxic responses, 2) increase of neutrophil adhesiveness to cell-free surfaces, and 3) inhibition of chemotactic responses to FMLP. These findings suggest that H2O2 may play a major role in neutrophil activation induced by PMA.     

Polyclonal activation of lymphocytes induced in the mouse by acebutolol, a beta blocking agent

Acebutolol, a beta blocking agent, was injected at a dose of 1 mg/day, every day for 6 months in C57B1/6 and OF1 mice. No antinuclear antibodies were induced but a transient induction of anti-single stranded DNA antibodies and an increase of IgM, IgA and IgG2a levels were observed during the first 3 weeks in some treated mice as compared to control mice. This effect was more pronounced in C57B1/6 than in OF1 mice and in the C57B1/6 mice, was more frequently observed in female than in male mice. It was further found by cellular studies done in C57B1/6 female mice, that daily i.p. or oral administration of Acebutolol induces a transient polyclonal stimulation of lymphocytes. It is concluded that certain beta blockers might possess some in vivo effects on the immune system.     

Involvement of catalase in the protective effect of binaphthyl diselenide against renal damage induced by glycerol

In the present study, the protective effect of binapthyl diselenide [(NapSe)₂] was investigated on glycerol-induced renal damage in rats. Adult male Wistar rats were treated with (NapSe)₂ (50 mg/kg, orally) or vehicle. After 24 h (NapSe)₂ treatment, the animals received an intramuscular injection of glycerol (8 ml/kg, dissolved in saline) or vehicle as a divided dose into the hind limbs. Twenty-four hours afterwards, rats were euthanized and the levels of urea and creatinine were measured in plasma. Non-protein thiol (NPSH) levels and catalase (CAT) activity were evaluated in renal homogenates. Histopathological evaluations were also performed in kidneys of rats. The rats exposed to glycerol presented swelling of the proximal and distal tubules with evidence of cell damage and death. Glycerol-exposed rats presented an increase in renal failure markers (plasmatic urea and creatinine levels) and a reduction in renal CAT activity. No change was observed in NPSH levels in kidneys of rats exposed to glycerol. (NapSe)₂ protected against the alterations caused by glycerol in rats. (NapSe)₂ increased per se NPSH levels (33%) in kidneys of rats. In conclusion, the results demonstrated that treatment with (NapSe)₂ protected against renal damage induced by glycerol in rats, probably due to its antioxidant effect.     

Involvement of catecholamine neurotransmission in the rat anterior cingulate in effort-related decision making

This study examined whether catecholamine-mediated signals in the anterior cingulate cortex (ACC) contribute to effort-based decision making. Rats were tested after 6-hydroxydopamine or vehicle infusions into the ACC in a T maze cost-benefit task in which the rats could choose either to climb a barrier to obtain a high reward in one arm or run into the other arm without a barrier to obtain a low reward. Results demonstrate that infusions of 6-hydroxydopamine induced a near total loss of tyrosine hydroxylase-positive fibers in the ACC. Unlike sham-lesioned rats, 6-hydroxydopamine-lesioned rats exhibited a reduced preference for the high-cost-high-reward response option when given the choice of obtaining a low reward with little effort. Thus, catecholamine-mediated signals in the ACC could play a role in effort-based decision making.     

Isoflurane preconditioning reduces mouse microglial activation and injury induced by lipopolysaccharide and interferon-gamma

Activation and injury of microglial cells are involved in a broad range of brain diseases including stroke, brain infection and neurodegenerative diseases. However, there is very little information regarding how to reduce microglial reaction and preserve these cells to provide neuroprotection. Here, we showed that the incubation of C8-B4 mouse microglial cells with lipopolysaccharide (LPS) plus interferon-gamma (IFNgamma) for 24 h decreased the viability of these cells. Pretreatment of these cells with 1%, 2% or 3% isoflurane, a commonly used volatile anesthetic, for 1 h at 30 min before the exposure to LPS plus IFNgamma attenuated the reduction of cell viability (preconditioning effect). LPS plus IFNgamma also activated these microglial cells to express inducible nitric oxide synthase (iNOS) and to induce accumulation of nitrite, a stable oxidation product of nitric oxide, in the incubation medium. Isoflurane preconditioning attenuated these LPS plus IFNgamma effects on the iNOS expression and nitrite accumulation. Aminoguanidine, an iNOS inhibitor, attenuated the LPS plus IFNgamma-induced glutamate release and decrease of microglial viability. Isoflurane preconditioning also reduced LPS plus IFNgamma-induced glutamate release. Exogenous glutamate decreased microglial viability. Finally, the isoflurane preconditioning-induced protection was abolished by chelerythrine, a protein kinase C inhibitor. These results suggest that LPS plus IFNgamma activates the iNOS-nitric oxide-glutamate pathway to induce microglial injury and that this activation is attenuated by isoflurane preconditioning. Protein kinase C may be involved in the isoflurane preconditioning effects.     

Spinal cord mechanisms mediating behavioral hyperalgesia induced by neurokinin-1 tachykinin receptor activation in the rostral ventromedial medulla

Hyperalgesia in animal injury models is linked to activation of descending raphespinal modulatory circuits originating in the rostral ventromedial medulla (RVM). A neurokinin-1 (NK-1) receptor antagonist microinjected into the RVM before or after inflammation produced by complete Freund's adjuvant (CFA) resulted in an attenuation of thermal hyperalgesia. A transient (acute) or a continuous infusion of Substance P (SP) microinjected into the RVM of non-inflamed animals led to similar pain hypersensitivity. Intrathecal pretreatment or post-treatment of a 5-HT3 receptor antagonist (Y-25130 or ondansetron) blocked the SP-induced hyperalgesia. The SP-induced hyperalgesia was both GABA(A) and NMDA receptor-dependent after pre- and post-treatment with selective antagonists at the spinal level. A microinjection of SP into the RVM also led to increased NMDA NR1 receptor subunit phosphorylation in spinal cord tissue. The GABA(A) receptor-mediated hyperalgesia involved a shift in the anionic gradient in dorsal horn nociceptive neurons and an increase in phosphorylated NKCC1 protein (isoform of the Na-K-Cl cotransporter). Following a low dose of SP infused into the RVM, intrathecal muscimol (GABA(A) agonist) increased SP-induced thermal hyperalgesia, phosphorylated NKCC1 protein expression, and NMDA NR1 subunit phosphorylation in the spinal cord. The thermal hyperalgesia was blocked by intrathecal gabazine, the GABA(A) receptor antagonist, and MK-801, the NMDA receptor channel blocker. These findings indicate that NK-1 receptors in the RVM are involved in SP-induced thermal hyperalgesia, this hyperalgesia is 5-HT3-receptor dependent at the spinal level, and involves the functional interaction of spinal GABA(A) and NMDA receptors.     

Effect of hypotension induced by sodium nitroprusside on catecholamine overflow in the canine kidney

The overflow of noradrenaline (NA) and dopamine (DA) to plasma in the kidney in response to hypotension induced by sodium nitroprusside were studied in barbiturate-anaesthetized dogs in order to evaluate the possible existence of separately regulated renal noradrenergic and dopaminergic nerve fibres. When mean arterial blood pressure was lowered to 55 +/- 5 mmHg, arterial plasma NA, DA and adrenaline concentrations were increased and renal blood flow decreased. Renal sympathetic nerve activity was assessed by measuring the renal overflow of catecholamines to plasma. To obtain more accurate estimates of the renal contribution to catecholamines in renal venous plasma we corrected for the renal extraction of arterial catecholamines, assessed by the extraction of endogenous adrenaline. The corrected renal NA overflow to plasma increased from 164 +/- 52 to 419 +/- 137 pmol min-1 (P less than 0.05) during sodium nitroprusside induced hypotension. The renal overflow of DA to plasma was, however, not influenced significantly. The DA/NA ratio for renal venous plasma concentration as well as for renal overflow to plasma was decreased (P less than 0.05) by sodium nitroprusside induced renal nerve activation. In contrast, electrical renal nerve stimulation has previously been shown to enhance the overflows of DA and NA in parallel. One possible interpretation of these findings is that sodium nitroprusside selectively activated renal noradrenergic but not the putative dopaminergic nerve fibres while electrical stimulation activated both types of fibres.