Short-term neuronal effects of fumonisin B1 on neuronal activity in rodents

Fumonisin B1 (FB1) is a mycotoxin produced by microscopic fungi (mostly Fusarium species), which may infect our major crops. The toxin inhibits the development of these plants and may also have harmful effects on animals and humans consuming the infected crops.FB1 inhibits sphingolipid biosynthesis which leads to altered membrane characteristics and consequently, altered cellular functions. There are some indications that the toxin has inhibitory effects on neuronal activity in case of repeated consumption, presumably due to sphingolipid depletion. However, according to new literature data, FB1 may have acute excitatory neural effects, too, via different mechanisms of action. Therefore, in the present study, we addressed the neuronal network effects of FB1 following acute treatment, using different electrophysiological techniques in vitro and in vivo.Acute treatments with FB1 (10–100 μM) were carried out on brain slices, tissue cultures and live animals. After direct treatment of samples, electrically evoked or spontaneous field potentials were examined in the hippocampus and the neocortex of rat brain slices and in hippocampal cell cultures. In the hippocampus, a short-term increase in the excitability of neuronal networks and individual cells was observed in response to FB1 treatment. In some cases, the initially enhanced excitation was reversed presumably due to overactivation of neuronal networks. Normal spontaneous activity was found to be stimulated in hippocampal cell cultures. Seizure susceptibility was not affected in the neocortex of brain slices.For the verification of the results caused by direct treatment, effects of systemic administration of FB1 (7.5 mg/kg, i.p.) were also examined. Evoked field potentials recorded in vivo from the somatosensory cortex and cell activation measured by the c-fos technique in hippocampus and somatosensory cortex were analyzed. However, the hippocampal and cortical stimulatory effect detected in vitro could not be demonstrated by these in vivo assays.Altogether, the toxin enhanced the basic excitability of neurons and neuronal networks after direct treatment but there were no effects on the given brain areas after systemic treatment in vivo. Based on the observed in vitro FB1 effects and the lack of data on the penetration of FB1 across the blood-brain barrier, we assume that in vivo consequences of FB1 administration can be more prominent in case of perturbed blood-brain barrier functions.     

经颅磁刺激对脑梗死大鼠皮质c-Fos和BDNF表达的影响

目的研究经颅磁刺激(TMS)对脑梗死大鼠梗死侧皮质c-Fos、脑源性神经营养因子(BD-NF)表达的影响。方法采用80只SD大鼠制作一侧永久性大脑中动脉闭塞的脑梗死模型,随机分为模型组和TMS组。模型组自由饲养;TMS组于动物清醒后当天即给予每天2次、每次30个脉冲的TMS治疗(频率为0.5Hz,场强为1.33T)。各组在大鼠脑梗死后1,7,14,21和28d(每时间点8只)检测梗死侧大脑皮质c-Fos、BDNF的表达。结果模型组和TMS组梗死灶周围皮质均可见c-Fos和BDNF的阳性表达,与模型组相同时间点比较,TMS组7,14,21和28d时c-Fos表达较高,差异有统计学意义(P<0.05),7,14和21d时BD-NF表达较高,差异有统计学意义(P<0.01)。结论TMS能促进大鼠脑梗死后梗死侧皮质c-Fos和BDNF的表达,从而发挥其脑保护及康复治疗效应。     

Functional Connections of the Vestibulo-spino-adrenal Axis in the Control of Blood Pressure Via the Vestibulosympathetic Reflex in Conscious Rats

Significant evidence supports the role of the vestibular system in the regulation of blood pressure during postural movements. In the present study, the role of the vestibulo-spino-adrenal (VSA) axis in the modulation of blood pressure via the vestibulosympathetic reflex was clarified by immunohistochemical and enzyme immunoassay methods in conscious rats with sinoaortic denervation. Expression of c-Fos protein in the intermediolateral cell column of the middle thoracic spinal regions and blood epinephrine levels were investigated, following microinjection of glutamate receptor agonists or antagonists into the medial vestibular nucleus (MVN) and/or sodium nitroprusside (SNP)-induced hypotension. Both microinjection of glutamate receptor agonists (NMDA and AMPA) into the MVN or rostral ventrolateral medullary nucleus (RVLM) and SNP-induced hypotension led to increased number of c-Fos positive neurons in the intermediolateral cell column of the middle thoracic spinal regions and increased blood epinephrine levels. Pretreatment with microinjection of glutamate receptor antagonists (MK-801 and CNQX) into the MVN or RVLM prevented the increased number of c-Fos positive neurons resulting from SNP-induced hypotension, and reversed the increased blood epinephrine levels. These results indicate that the VSA axis may be a key component of the pathway used by the vestibulosympathetic reflex to maintain blood pressure during postural movements.     

Withdrawal of repeated morphine enhances histamine-induced scratching responses in mice

An itch is experientially well known that the scratching response of conditions such as atopic dermatitis is enhanced under psychological stress. Morphine is typical narcotic drug that induces a scratching response upon local application as an adverse drug reaction. Although long-term treatment with morphine will cause tolerance and dependence, morphine withdrawal can cause psychologically and physiologically stressful changes in humans. In this study, we evaluated the effects of morphine withdrawal on histamine-induced scratching behavior in mice. Administration of morphine with progressively increasing doses (10–50?mg/kg, i.p.) was performed for 5 consecutive days. At 3, 24, 48, and 72?hr after spontaneous withdrawal from the final morphine dose, histamine was intradermally injected into the rostral part of the back and then the number of bouts of scratching in 60?min was recorded and summed. We found that at 24?hr after morphine withdrawal there was a significant increase in histamine-induced scratching behavior. The spinal c-Fos positive cells were also significantly increased. The relative adrenal weight increased and the relative thymus weight decreased, both significantly. Moreover, the plasma corticosterone levels changed in parallel with the number of scratching bouts. These results suggest that morphine withdrawal induces a stressed state and enhances in histamine-induced scratching behavior. Increased reaction against histamine in the cervical vertebrae will participate in this stress-induced itch enhancement.     

七氟醚对兔肝缺血/再灌注损伤后肝组织丙二醛、血浆丙氨酸转氨酶和谷草转氨酶活性及c-Fos蛋白的表达的影响

目的 探讨七氟醚麻醉对兔肝缺血/再灌注损伤(ischemia/reperfusion injury,Ⅰ/RI)的影响. 方法 健康成年新西兰大白兔21只,按照随机数字表法分为3组(每组7例):假手术组(S组)、肝Ⅰ/R组(Ⅰ/R组)、七氟醚麻醉组(Sev-Ⅰ/R组).结扎肝动脉建立兔肝脏Ⅰ/RI模型,分别于缺血前(Tl)、缺血45 min(T2)和再灌注60 min(T3)测定血浆丙氨酸转氨酶(aspartate a minotransferase,AST)及谷草转氨酶(alanine aminotransferase,ALT)水平,于T3测定肝组织丙二醛(malondialdehyde,MDA)含量;免疫组化染色检测c-Fos蛋白的表达情况. 结果 与S组比较,Ⅰ/R组血浆ALT和AST活性[T2:(48±6) U/L和(48±7) U/L,T3:(66±6) U/L和(70±6)U/L]及Sev-Ⅰ/R组血浆ALT和AST活性[T2:(43±7) U/L和(41±3) U/L,T3:(48±6) U/L和(50±6) U/L]、肝组织MDA含量和c-Fos蛋白表达水平均明显升高(P＜0.05或P＜0.01);Sev-Ⅰ/R组所有这些实验指标均明显低于Ⅰ/R组(P＜0.05或P＜0.01). 结论 七氟醚对Ⅰ/RI兔肝组织有保护作用,可与其降低活性氧产物有关.     

Changes in dopamine transporter and c-Fos expression in the nucleus accumbens of alcohol-tolerant rats

BACKGROUND: We have shown that neurochemical functions of 5-HT3 receptors in regulating dopamine (DA) release in the nucleus accumbens (ACC) after alcohol exposure compensate for the dysfunction of serotonergic activity to restore the original properties in processing alcohol tolerance, and that the development of alcohol dependence may be mediated by ACC 5-HT3 receptors. In the present study, the effects of chronic alcohol consumption on the functions of the dopamine transporter (DAT) and the expression of c-Fos proteins were investigated using in vivo brain microdialysis and immunocytochemistry. METHODS: Perfusion of cocaine and 1-(2-Bis-(4-fluorophenyl) methoxy) ethyl)-4-(3-phenylpropyl) piperizine (GBR 12909) through the microdialysis probe membrane increased the extracellular levels of DA in ACC of alcohol-treated rats that had developed alcohol tolerance by drinking 10% EtOH for 30 days. RESULTS: The magnitudes of DA reuptake or DAT inhibitors, cocaine, and GBR 12909 that induced DA availability in the ACC were significantly higher in alcohol-treated rats than in controls. When compared with control rats, the alcohol-treated rats exhibited higher levels of DA and its metabolite, DOPAC, in the ACC. Increased expression of the c-Fos-like protein was found in the ACC of alcohol-treated rats. These results show that (1) chronic alcohol consumption desensitizes or decreases the DAT of DA terminals in the ACC and that (2) EtOH causes cellular hyperexcitability of ACC dopaminergic neurons with increased Fos expression during alcohol tolerance. CONCLUSION: The findings suggested that an abnormality of the dopaminergic neurons in the ACC that are involved with DAT dysfunction is associated with the development of alcohol tolerance.     

环境温度变化对去卵巢大鼠下丘脑视上核和室旁核c-Fos蛋白表达的影响

目的:以不同温度刺激去卵巢大鼠,观察下丘脑视上核(SO)和室旁核(PVN)细胞c-Fos蛋白表达的变化,探讨更年期妇女血压、渗透压以及体温调节功能异常的可能机制.方法:将去卵巢(OVX)和假手术(Sham)大鼠分别置于4,10,25,33和38℃5个温度等级的培养箱内,2 h后取脑.采用免疫组织化学法检测各实验组SO和...     

中药复方液对麻黄素仔鼠肝组织结构和抗氧化酶活性的影响

目的 探讨中药复方液对麻黄素致损伤的影响。 方法 采用递增剂量连续腹腔注射浓度为2.0g/L、3.0g/L和4.0g/L的麻黄素溶液,在注射麻黄素1h 后再分别灌胃,浓度为20.0g/L、30.0g/L和40.0g/L的中药复方液。分别于灌胃中药5、10、15d后,用比色法测定仔鼠肝组织中超氧化物歧化酶（SOD）、过氧化氢酶（CAT）活性和丙二醛（MDA）含量,用显微镜观察肝组织结构,用免疫组织化学法检测肝组织c-Fos蛋白的表达。 结果 麻黄素组仔鼠10d、15d 时肝组织SOD、CAT的活性低于对照组,MDA含量高于对照组 (P<0.05或 P<0.01),肝组织有不同程度的损伤,肝组织c-Fos蛋白表达强度高于对照组 (P<0.05或P<0.01);中药组仔鼠肝组织SOD、CAT活性升高,MDA含量降低(P<0.05或P<0.01),肝组织损伤明显减轻,肝组织c-Fos蛋白的阳性表达强度减弱(P<0.05或P<0.01)。结论 麻黄素对肝组织有明显的损伤效应,中药复方液可提高细胞抗氧化活性,具有抗炎、抗氧化和保护肝细胞等作用,能有效减轻麻黄素对肝组织的损伤。     

Effects of testosterone and estradiol on anxiety and depressive-like behavior via a non-genomic pathway

Besides their known slow genomic effects, testosterone and estradiol have rapid effects in the brain. However, their impact on mood-related behavior is not clear. The aim of this study was to investigate the non-genomic pathway of testosterone and estradiol in the amygdala in relation to anxiety and depressive-like behavior. Sham-operated and gonadectomized male rats(GDX) supplemented with testosterone propionate, estradiol, or olive oil were used. Five minutes after administration, anxiety and depression-like behavior were tested. Estradiol increased anxiolytic behavior in the open-field test compared to the GDX group, but administration of testosterone had no significant effect. Besides, c-Fos expression in the medial nucleus of the amygdala significantly increased after testosterone treatment compared to the GDX group, while no significant difference was observed in the central and the basolateral nuclei of the amygdala in the testosterone-treated group compared to the GDX group. In conclusion, estradiol had an anxiolytic effect via a rapid pathway, but no rapid effect of testosterone on anxiety was found. Further studies elucidating whether the rapid effect is mediated by a non-genomic pathway are needed.     

氯胺酮抑制昆明小鼠扣带后回Fos表达

目的 探讨慢性氯胺酮使用对扣带后回c -Fos与磷酸化的转录因子环磷酸腺苷反应元件结合蛋白(cAMP responsive element binding protein,CREB)的影响.方法 成年昆明小鼠,采用随机数字表法分组:腹腔注射50、100、200 mg/kg组以及生理盐水组,5d给药1次,共注射6次后4％多聚甲醛灌注固定、取脑、30μm冰冻切片,应用免疫组化法检测c-Fos和磷酸化cAMP反应元件结合蛋白(phosphorylated cAMP responsive element binding protein,pCREB)的表达.结果 ①扣带后回和压部后皮质有一定的c -Fos与pCREB基础;②氯胺酮慢性使用扣带后回神经元的c-Fos表达减少,50 mg/kg组、100 mg/kg组、200 mg/kg组分别下降到生理盐水组的80％、43％和37％.而pCREB的表达增加,50 mg/kg组、100 mg/kg组、200 mg/kg组分别增加到生理盐水组的180％、195％和170％.结论 慢性氯胺酮使用抑制昆明小鼠扣带后回神经元c-Fos表达,其抑制可能与pCREB表达增加有关.