Arginine vasopressin in the caudate nucleus plays an antinociceptive role in the rat

Our previous work has shown that arginine vasopressin (AVP) regulates antinociception through brain nuclei rather than the spinal cord and peripheral organs. The present study investigated the nociceptive effect of AVP in the caudate nucleus (CdN) of the rat. Microinjection of AVP into the CdN increased pain threshold in a dose-dependent manner, while local administration of AVP-receptor antagonist-d(CH(2))(5)Tyr(Et)DAVP decreased pain threshold. Pain stimulation elevated AVP concentration in CdN perfuse liquid. CdN pretreatment with AVP-receptor antagonist completely reversed AVP's effect on pain threshold in the CdN. The data suggest that AVP in the CdN is involved in antinociception.     

Melatonin prevents oxidant damage in various tissues of rats with hyperthyroidism

Impairment of thyroid functions brings about pathological changes in different organs of body. Findings of in vivo and in vitro studies indicate that thyroid hormones have a considerable impact on oxidative stress. Melatonin reduces oxidative damage through its free radical eliminating and direct anti-oxidant effects. The present study was undertaken to determine how a 3-week period of intraperitoneal melatonin administration affected oxidative damage caused in experimental hyperthyroidism in rat. The experimental animals were divided into 3 groups (control, hyperthyroidism, hyperthyroidism+melatonin). Malondialdehyde (MDA) and glutathione (GSH) levels were determined in different tissues. MDA levels in cerebral, liver and cardiac tissues in hyperthyroidism group were significantly higher than those in control and hyperthyroidism+melatonin supplemented groups (p<0.001). The highest GSH levels were observed in the group that was administered melatonin in addition to having hyperthyroidism (p<0.001). These results show that hyperthyroidism increased oxidative damage in cerebral, hepatic and cardiac tissues of rat. Melatonin supplementation may also suppress oxidative damage.     

Influences of isotonic, hypertonic and hypovolemic treatments on vasopressin response and fluid-electrolyte balance in l-thyroxine-induced hyperthyroid rat

The present study was performed to determine how l-thyroxine-induced hyperthyroidism affects the vasopressin response to different stimulations (isotonic, hypertonic and hypovolemic) in rats. Spraque-Dawley rats were initially separated into 3 groups; control (n=24), sham hyperthyroidism (n=24, hyperthyroidism (n=24). At the end of the experiment additional sub-groups were formed before decapitation. These sub-groups were formed as; without stimulation (n=6), isotonic stimulation (n=6), hypertonic stimulation (n=6) and hypovolemic stimulation (n=6). Total T3, total T4 and AVP levels were evaluated in the plasma. Haematocrit and osmolality levels were also determined. When the parameters related to thyroid hormones were evaluated, it was determined that total T3 and T4 levels were higher in hyperthyroid group than the other groups. Plasma AVP levels showed more increase in hyperthyroid group both in basal grade and against to hypertonic and hypovolemic stimulations than the other groups (P<0.001). The results of the present study indicate that l-thyroxine-induced experimental hyperthyroidism increased basal and stimulated AVP release in rats.     

Age-related changes of the GABA-B receptor in the lumbar spinal cord of male rats and penile erection

Dorsal horn neurons of lumbosacral spinal cord innervate penile vasculature and regulate penile erection. GABAergic system is involved in the regulation of male sexual behavior. Because aging is frequently accompanied by a progressive decline in erectile function, the aim of this work was to examine age-related changes of the GABA-B receptor in the lumbar spinal cord. Sprague-Dawley rats of 10 and 21 days old, 3, 9 and 20 months old were used. GABA-B receptors were evaluated by quantitative autoradiography using [3H]-Baclofen as ligand with or without GABA (10 microM) to determine the non-specific binding. Ten days after birth a homogeneous neuroanatomical distribution pattern was found in the gray matter, however at 20-day-old adult distribution emerged becoming heterogeneous with the highest binding values at layers II-III and X. In dorsal layers a significant decrease was observed in 9-month-old rats while layer X showed an earlier decrease (21-day-old). GABA-B receptor affinity showed significant age-dependent and regional increase. The GABA-B receptor decrease in aged rats seems not to be related to this receptor inhibitory function in penile erection. Moreover the changes found in GABA-B receptor binding anatomical distribution may indicate its role in the morphological development of the lumbar spinal cord rather than in the decline of the erectile function.     

Benzo(alpha)pyrene-induced up-regulation of CYP1A2 gene expression: role of adrenoceptor-linked signaling pathways

CYP1A2, a principal catalyst for metabolism of various therapeutic drugs and carcinogens, among others, is in part regulated by the stress response. This study was designed to assess whether catecholamines and in particular adrenergic receptor-dependent pathways, modulate benzo(alpha)pyrene (B(alpha)P)-induced hepatic CYP1A2. To distinguish between the role of central and peripheral catecholamines in the regulation of CYP1A2 induction, the effect of central and peripheral catecholamine depletion using reserpine was compared to that of peripheral catecholamine depletion using guanethidine. The effects of peripheral adrenaline and L-DOPA administration were also assessed. The results suggest that alterations in central catecholamines modulate 7-methoxyresorufin O-demethylase activity (MROD), CYP1A2 mRNA and protein levels in the B(alpha)P-induced state. In particular, central catecholamine depletion, dexmedetomidine-induced inhibition of noradrenaline release and blockade of alpha(1)-adrenoceptors with prazosin, up-regulated CYP1A2 expression. Phenylephrine and dexmedetomidine-induced up-regulation may be mediated, in part, via peripheral alpha(1)- and alpha(2)-adrenoceptors, respectively. On the other hand, the L-DOPA-induced increase in central dopaminergic activity was not followed by any change in the up-regulation of CYP1A2 expression by B(alpha)P. Central noradrenergic systems appeared to counteract up-regulating factors, most likely via alpha(1)- and alpha(2)-adrenoceptors. In contrast, peripheral alpha- and beta-adrenoceptor-related signaling pathways are linked to up-regulating processes. The findings suggest that drugs that bind to adrenoceptors or affect central noradrenergic neurotransmission, as well as factors that challenge the adrenoceptor-linked signaling pathways may deregulate CYP1A2 induction. This, in turn, may result in drug-therapy and drug-toxicity complications.     

General administration of cyclohexenonic long-chain fatty alcohol ameliorates hyperreactivity of STZ-induced diabetic rat aorta

Diabetic neuropathy, a major complication of diabetes mellitus, is associated with the development of vascular dysfunction and autonomic neuropathy. We studied the effects of cyclohexenonic long-chain fatty alcohol (FA) on streptozotocin-diabetic hyperreactivity in the rat aorta smooth muscle. The rats were divided randomly into four groups and were maintained for 4 weeks: age-matched control rats, diabetic rats without treatment with FA, and diabetic rats treated with FA (2 and 8 mg/kg, i.p. everyday). The serum glucose and insulin levels were determined, and the contractile responses of the aorta induced by a thromboxane A2 agonist, U46619 and KCl were investigated. Treatment with FA did not alter rats' diabetic status, i.e., body weight, thickness of the aorta, serum glucose levels, and serum insulin levels, but significantly improved the diabetic-induced hyperreactivity of the rat aorta in a dose-dependent manner. Removal of endothelium did not change contractile force between groups. In histological examinations, thinning of smooth muscle bundle in the wall of aorta was observed in the diabetic rat, which was not significantly improved by treatment with FA. Our data indicate that FA can prevent hyperreactivity in the diabetic aorta.     

慢性复合应激对大鼠学习和记忆及海马神经元神经颗粒素表达的影响

目的探讨慢性复合应激对大鼠学习和记忆功能及海马内神经元神经颗粒素(neurogranin,Ng)表达的影响。方法成年雄性Wistar大鼠随机分为对照组和复合应激组,复合应激组动物每天无规律交替暴露于复合应激原环境中,为期6周。应激结束后,用Morris水迷宫测试大鼠空间学习和记忆成绩,同时用免疫组织化学方法观察海马各亚区Ng表达的变化,并用RT-PCR技术分析各组大鼠海马Ng mRNA水平的变化。结果Morris水迷宫测试显示,应激组动物寻找隐蔽平台潜伏期明显短于对照组(P<0.05);应激组大鼠海马DG和CA3区Ng的蛋白表达水平明显高于对照组(P<0.05),而两组海马CA1区的Ng的免疫反应性无明显差别;与对照组相比,应激组动物的Ng mRNA水平亦明显上调(P<0.05)。结论慢性复合性应激大鼠的学习与记忆能力增强;Ng在海马中的表达和Ng mRNA转录水平增高,提示Ng参与了该增强机制。     

Tropic 1808基因重组蛋白对大鼠坐骨神经再生的影响

目的观察Tropic1808基因重组蛋白对坐骨神经损伤后再生的影响。方法SD大鼠16只,分为Tropic1808基因重组蛋白组和生理盐水组,切断左侧坐骨神经,硅胶管套接后两神经断端间距10mm,再生室内注入Tropic 1808基因重组蛋白液(500μg/ml)或生理盐水13μl。术后每4周做一次足迹试验,16周时作神经干动作电位、脊髓前角运动神经元数、腓肠肌纤维截面积、硅胶管中段再生神经等检测。结果Tropic1808基因重组蛋白组SFI的恢复、神经干动作电位、脊髓前角运动神经元数、腓肠肌纤维截面积、硅胶管中段再生神经有髓神经纤维数等结果均明显优于生理盐水组,有统计学意义。电镜观察表明Tropic1808组再生轴突较NS组粗,髓鞘较生理盐水组厚。结论Tropic1808基因重组蛋白有促进大鼠坐骨神经再生的作用。     

基于IPA分析自噬对大鼠肝再生中树突状细胞的调节作用

为探讨自噬对大鼠肝再生中树突状细胞(Dendritic cells, DCs)的调节作用,文章通过Percoll 密度梯度离心结合免疫磁珠分选分离大鼠DCs,Rat Genome 230 2.0芯片检测大鼠肝再生中自噬相关基因表达变化,利用IPA等软件分析自噬在DCs中的生理活动。结果表明,LC3、BECN1、ATG7和SQSTM1等关键基因在部分肝切除后不同恢复时间段有明显表达变化;芯片中对应的自噬相关基因为593个,其中210个基因发生了有意义的变化。比较分析自噬生理活动情况,发现自噬在再生早期和晚期阶段增强,增殖期减弱。与自噬相关的生理活动主要有RNA表达、RNA转录细胞分化和增殖,其中涉及的信号通路主要有PPARα/RXRα激活、急性期反应、TREM1 信号通路、IL-6 信号通路、IL-8 信号通路和IL-1 信号通路等,它们在肝再生阶段发生了不同程度的上调或下调。Cluster 分析还发现,P53和AMPK信号参与调控DCs的自噬活动,在肝再生早期主要是AMPK信号,在肝再生末期P53和AMPK信号共同参与自噬的调节。以上研究结果说明DCs自噬可能在肝再生早期激活细胞免疫反应和后期清除DCs等方面发挥着重要作用。     

Rho-associated kinase connects a cell cycle-controlling anchorage signal to the mammalian target of rapamycin pathway

When deprived of anchorage to the extracellular matrix, fibroblasts arrest in G(1) phase at least in part due to inactivation of G(1) cyclin-dependent kinases. Despite great effort, how anchorage signals control the G(1)-S transition of fibroblasts remains highly elusive. We recently found that the mammalian target of rapamycin (mTOR) cascade might convey an anchorage signal that regulates S phase entry. Here, we show that Rho-associated kinase connects this signal to the TSC1/TSC2-RHEB-mTOR pathway. Expression of a constitutively active form of ROCK1 suppressed all of the anchorage deprivation effects suppressible by tsc2 mutation in rat embryonic fibroblasts. TSC2 contains one evolutionarily conserved ROCK target-like sequence, and an alanine substitution for Thr(1203) in this sequence severely impaired the ability of ROCK1 to counteract the anchorage loss-imposed down-regulation of both G(1) cell cycle factors and mTORC1 activity. Moreover, TSC2 Thr(1203) underwent ROCK-dependent phosphorylation in vivo and could be phosphorylated by bacterially expressed active ROCK1 in vitro, providing biochemical evidence for a direct physical interaction between ROCK and TSC2.