糖尿病大鼠下丘脑中胃动素的表达及中枢注射红霉素对胃运动的影响(英文)

目的以往的研究表明胃动素存在于大鼠的中枢神经系统,在中枢注射胃动素具有促进清醒大鼠胃运动的作用。但糖尿病大鼠中枢胃动素表达含量及中枢注射胃动素对糖尿病大鼠胃运动的潜在作用目前尚未报导。本研究探索糖尿病大鼠胃动素免疫阳性神经元在下丘脑的表达,观察侧脑室微量注射胃动素受体激动剂红霉素(erythromycin, EM)对正常和糖尿病大鼠胃运动的作用。方法采用免疫组织化学方法测定下丘脑胃动素免疫阳性神经元的分布特征。在胃窦浆膜层植入应力传感器,测定清醒大鼠胃运动的幅度和频率。结果糖尿病大鼠下丘脑室旁核和视上核胃动素免疫阳性神经元数量明显高于正常对照大鼠(P<0.05)。脑室内微量注射EM可以明显促进糖尿病大鼠的胃运动。注射91.56nmol的EM五分钟后,大鼠胃窦运动幅度升高(174.82±48.62)%(P<0.05),运动频率加快(70.43±27.11)% (P<0.05)。在脑室内微量注射胃动素拮抗剂GM-109后,再注射EM, 其促胃运动效应可被部分阻断。结论糖尿病大鼠中枢胃动素对胃运动有一定的调制作用,而且脑室内微量注射的EM是通过脑内的胃动素受体介导而发挥其促胃动力效应。     

不同强度运动对糖尿病大鼠认知功能的影响及机理探索

目的 观察对比不同强度运动对糖尿病大鼠认知功能的影响及其机制.方法 将SD大鼠随机分组,正常对照组10只,模型组30只为链脲佐菌素(streptozotocin,STZ)造模成功的1型糖尿病模型.模型组义分为阳性对照组(未游泳),1 h/d游泳组和力竭游泳组,每组10只.在3个月时进行开场实验测试活动度和探索能力,Morris水迷宫测试空间搜索和学习记忆能力,免疫组织化学方法检测脑部海马区纤维连接蛋白(fibronectin,Fn),反映脑内纤维增生及退行性变情况.结果 阳性对照组大鼠学习记忆与正常对照组相比显著下降(P＜0.05),1 h/d游泳组明显好于阳性对照组(P＜0.05),力竭游泳组效果不明显(P＞0.05).正常对照组和1 h/d游泳组比阳性对照组海马厌脑组织Fn阳性区域显著减少(P＜0.05).结论 适度运动可以改善糖尿病模型大鼠的学习记忆和探索能力,究其机理与运动可抑制脑组织退行性变密切相关.     

冈田酸诱导大鼠脑tau蛋白磷酸化和神经细胞退化

采用免疫组织化学、荧光双标记技术及大鼠额叶皮质定位注射OA的方法,观察和研究蛋白磷酸酶抑制剂冈田酸(okadaic acid,OA)对大鼠脑tau蛋白高度磷酸化和神经细胞退化的影响,结果表明:①AT8免疫组织化学染色观察到在20 ng OA作用下神经细胞突起远端tau蛋白首先磷酸化,出现AT8即PHF-tau免疫阳性反应,并逐渐向胞体发展,形成营养不良的神经细胞突起和神经纤维缠结样神经细胞;②细胞计数表明额叶皮质注射20ng OA后12 h AT8免疫阳性神经细胞数显著增多(P＜0.01),1 d时达峰值(P＜0.01),3d后减少;注射OA 20,50,100 ng 1 d时均大量表达AT8阳性细胞(P＜0.05),但其各组间无显著差异;③免疫荧光双标记结果显示磷酸化tau蛋白在神经元和星形胶质细胞均存在,部分tau蛋白高度磷酸化的神经细胞TUNEL染色阳性,并伴有核浓缩断裂现象.这提示OA能有效诱导大鼠脑星形胶质细胞和神经元微管相关蛋白tau高度磷酸化,从而导致神经细胞DNA损伤;后者可能参与了OA诱导的神经细胞退化过程,其机制则有待阐明.     

大鼠脑缺血再灌注后不同时间段中枢组织ACTH样蛋白表达变化

目的采用免疫细胞化学技术,探讨大鼠脑缺血再灌注后不同时期中枢几个重要脑区促肾上腺皮质激素样阳性免疫物的表达变化。方法雄性Wistar大鼠70只,随机分成正常对照组、假手术对照组、脑缺血再灌注组。以颈动脉引流法行全脑缺血再灌注造模,术后分6h、24h、72h三个时间段取脑,脑组织恒冷箱连续冠状切片,免疫细胞化学ABC反应,图像分析系统行顶皮质1区、下丘脑室旁核、丘脑室旁核、海马CAl区促肾上腺皮质激素样阳性免疫面积、平均吸光度检测。结果镜下观察,促肾上腺皮质激素样阳性免疫物呈深棕色,深染胞核广泛分布于中枢皮质、海马、丘脑及下丘脑等各脑区,核仁清晰可辩。在丘脑及下丘脑区域散在分布有“串珠”状阳性纤维。图像分析结果显示,假手术对照组、脑缺血再灌注组两组阳性免疫面积和平均吸光度值呈同步变化。从术后6h开始,假手术对照组、脑缺血再灌注组两组均较正常对照组显著升高,术后24h达高峰(P<0.05),然后逐渐回落。在三个不同时间段,三组间均存在显著差异(P<0.05),术后6h及24h脑缺血再灌注组>假手术对照组>正常对照组;术后72h假手术对照组>正常对照组>脑缺血再灌注组。结论在脑缺血再灌注不同时间段,中枢神经元促肾上腺皮质激素样阳性免疫物表达呈现明显的时间规律;促肾上腺皮质激素可能在神经元功能调控、中枢内环境控制及脑缺血再灌注损伤过程中发挥重要作用。     

损毁下丘脑室旁核尿崩症动物模型的建立及评价

目的建立下丘脑室旁核损伤引起的中枢性尿崩症的大鼠模型.方法选择SD清洁级大鼠,采用立体定向技术向下丘脑室旁核注射海人藻酸而损毁之;对照组则注射人工脑脊液.注射30 min后收集1 h尿量,并用放免法检测血浆精氨酸加压素（AVP）水平,同时取注药部位的脑组织作组织学检查,观察室旁核神经元活性.结果下丘脑室旁核损毁后的大鼠尿量明显多于对照组（P＜0.05）;血浆AVP水平明显低于对照组（P＜0.05）.组织学观察表明实验组室旁神经元尼氏小体较对照组明显减少.结论在严格控制实验动物及实验条件前提下,采用立体定向技术损毁下丘脑室旁核建立尿崩症动物模型的方法是可行的.     

促红细胞生成素对血管性痴呆模型大鼠认知功能、脑保护作用及海马α-微管蛋白表达的影响

目的 研究促红细胞生成素(Epo)对血管性痴呆(VD)模型大鼠认知功能、脑保护作用和海马α-微管蛋白(tubulin)表达的影响.方法 用"两血管阻断 硝普钠降压"法建立大鼠VD模型,并给予Epo腹腔注射治疗,采用Morris水迷宫试验检测大鼠的认知功能,Nissle染色、α-tubulin免疫组化染色观察细胞形态和Western blot法检测海马α-tubulin表达水平.并与VD大鼠及假手术组大鼠比较.结果 与VD组比较,Epo组大鼠水迷宫试验逃避潜伏期明显缩短(除试验第1 d)(均P＜0.05);海马神经元形态规则,尼氏小体数量多,α-tubulin阳性轴突数多,α-tubulin含量显著升高(P＜0.05).而Epo组与假手术组水迷宫试验逃避潜伏期及海马α-tubulin含量差异无统计学意义.结论 Epo可改善VD大鼠的认知功能,减轻缺血性脑损害,促进海马α-tubulin的表达.     

Celecoxib对糖尿病大鼠缺血再灌注脑组织NF-κB和COX-2表达的影响

目的 探讨celecoxib对糖尿病大鼠脑缺血再灌注后脑组织中NF-κB和COX-2表达的影响.方法 采用SD大鼠腹腔注射链脲佐菌素(STZ)和线栓法制作糖尿病大鼠大脑中动脉缺血再灌注模型.大鼠分为假手术组(S组)、脑缺血再灌注生理盐水组(NS组)、celecoxib低剂量组(LCIR组)和高剂量组(HCIR组),分别于缺血后30min给予生理盐水或celecoxib溶液灌胃,再灌注后6、12、24、48h将大鼠断头取脑,免疫组化法检测脑组织中NF-κB和COX-2的表达.并对大鼠进行神经功能缺损评分.结果 NS组、LCIR组、HCIR组大鼠神经功能缺损评分有显著差异(P＜0.05);NS组、LCIR组、HCIR组阳性细胞主要表达于缺血周边区神经元中,较S组表达明显增强(P＜0.05),LCIR组、HCIR组阳性细胞表达率较NS组减少(P＜0.05),LCIR组、HCIR组之间未见明显差异(P＞0.05),每组不同时间点之间阳性细胞表达率有明显差异(P＜0.05).结论 celeeoxib可能通过抑制糖尿病大鼠脑缺血-再灌注后脑组织中NF-κB和COX-2的表达,减轻神经功能缺损,从而发挥脑保护作用.     

大鼠海马注射溶血磷脂酸诱导tau蛋白高度磷酸化和凋亡研究

目的研究溶血磷脂酸(LPA)在大鼠体内对海马神经细胞tau蛋白磷酸化水平的影响和诱导神经细胞凋亡的细胞毒性作用.方法将72只SD大鼠分为实验组(n=32)、实验对照组(n=32)和对照组(n=8),利用脑立体定位技术在大鼠双侧海马微量注射溶血磷脂酸、溶剂,于注射后12、24、48和72 h各不同时间点采用免疫组化方法测定该区域神经细胞中ser202位点磷酸化tau蛋白(PS202-tau)的表达,TUNEL技术检测细胞凋亡.结果实验组LPA注射后24 h海马CA4区神经细胞中PS202-tau阳性表达到达高峰,阳性表达高于对照组和实验对照组(P＜0.05).LPA注射后48 h TUNEL阳性细胞数达高峰,每个视野中阳性细胞数多于对照组和实验对照组(P＜0.05).结论LPA在动物整体水平可诱导大鼠海马神经细胞tau蛋白高度磷酸化,并导致神经细胞发生凋亡.     

血栓素A_2受体在正常大鼠脑内的分布定位

目的探讨血栓素A2受体(TP)在正常大鼠脑内的表达分布特点。方法正常成年SD大鼠脑组织冰冻切片,TP免疫荧光染色,TP/神经核蛋白(Neu N),TP/胶质纤维酸性蛋白(GFAP),TP/谷氨酸脱羧酶67(GAD67)免疫荧光双标染色,观察TP在脑内分布表达情况。结果 TP免疫阳性产物主要分布在扣带回皮质、皮层Ⅲ~V层、下丘和小脑的浦肯野细胞层;免疫荧光双标结果显示TP与神经元胞核特异性标记物Neu N共存,但不与星形胶质细胞标记物GFAP共存;同时,所有TP阳性神经元表达γ氨基丁酸(GABA)能神经元标记物GAD67。结论 TP表达于大鼠扣带回皮质、皮层Ⅲ~V层、下丘脑和小脑的浦肯野细胞层,主要分布于GABA能神经元,提示TP可能参与了大鼠大脑GABA能神经元的功能调节和病变过程。     

大鼠三联单叉神经中脑核内囊泡膜谷氨酸转运体样和GAD样阳性末梢与GABAA受体α1亚单位样阳性神经元的联系

最近已在哺乳类动物脑内克隆出两种新的脑内特殊的Na+依赖的无机磷酸转运体,它们均属于囊泡膜谷氨酸转运体,被分别命名为VGluTl(Vesicular glutamate transporter of type1)和DNPI(differentiation-associatedNa+-dependent inorganicphosphate eotransporter).本研究应用免疫荧光组织化学三重染色技术,在激光共聚焦显微镜下观察了大鼠三叉神经中脑核(Vine)内VGIuT1样和DNPI样以及谷氨酸脱羧酶(GAD)样阳性末梢与GABAA受体α1亚单位(GABAARa1)样阳性神经元之间的联系.结果显示:①几乎所有的Vme神经元均呈GABAA受体α1亚单位样免疫阳性,吻尾方向在其全长出现,这些神经元绝大多数为大的假单极神经元(直径为25～50um),但也有小部分为直径小于25um的神经元.②大量的VGluT1样和DNPI样免疫阳性的神经纤维和末梢广泛分布于Vine内,其中DNPI样阳性纤维和末梢的分布密度高于VGIuT1;同时还观察到GAD样阳性纤维和末梢也密集分布于Vme内.③VGluT1样、DNPI样和GAD样免疫阳性终扣分别包绕在GABAA受体α1亚单位样阳性Vine神经元胞体周围,并与之形成密切接触.以上结果提示:Vme神经元在介导面口部本体感觉信息的传递中,可能同时接受中枢其他来源的谷氨酸能和GABA能末梢的调控,其中GABA能的投射末梢可能通过位于Vine神经元内的GABAA受体对面口部本体感觉信息的传递发挥抑制性调控作用.     

The paraventricular nucleus modulates thyroidal motilin release and rat gastric motility

Motilin, an important endocrine regulator of gastrointestinal motility, was once considered to be produced in the gastrointestinal tract and brain. In recent years, however, motilin has been found in the human thyroid, as well as in that of the guinea pig. The physiological function and central modulation of thyroidal motilin remain poorly understood. To determine the functional role of thyroidal motilin, we observed the concentration of motilin in the plasma and also gastric motility before and after thyroidectomy. Our studies show that both the concentration of plasma motilin and gastric motility were decreased after thyroidectomy. To explore modulation-related nuclei, a c-Fos immune response experiment was carried out. The PVN of the hypothalamus was the main area of reactivity after thyroidectomy. Subsequently, we studied the effects of electrical excitation and PVN lesions on gastric motility and the expression of motilin in the thyroid and plasma. Excitation of the PVN was shown to prompt gastric motility that was partly prevented by the motilin receptor antagonist, GM-109. The effects of PVN excitation on gastric contraction were significantly reduced in thyroidectomised rats. In addition, the expression of motilin in the thyroid was significantly increased after PVN excitation and decreased after PVN lesions. The changes in the concentration of motilin in plasma induced by PVN stimulation were positively correlated with changes of gastric motility. In our in vitro study, the motilin secreted from TT cells (a parafollicular cell line originating from human thyroid medullary carcinoma) gradually increased on day 6 of culture, and motilin and calcitonin (CT) were co-expressed in TT cells. These results demonstrate that motilin from the thyroid could be secreted into the peripheral plasma and affect gastric motility and that PVN was a central nucleus for modulating gastric motility and motilin expression in the thyroid.     

Effect of motilin on gastric distension sensitive neurons in arcuate nucleus and gastric motility in rat

Background Intestinal motilin is known to stimulate gastrointestinal (GI) motility and the arcuate nucleus (Arc) of hypothalamus is shown to be involved in the regulation of GI motility. Methods Single unit discharges in the Arc were recorded extracellularly by implantation of a force transducer into the stomach in rats, to evaluate the effect of motilin on gastric motility. Projection of nerve fiber and expression of motilin were observed by retrograde tracer deposits of Fluoro‐Gold (FG) and fluo‐immunohistochemistry staining. Key Results 65.5% of neurons in Arc responded to gastric distension (GD), 55.6% of which showed excitation (GD‐E), and 44.4% showed inhibition (GD‐I). After GD, the firing rate of GD‐E neurons significantly increased (P < 0.01), but decreased for GD‐I neurons (P < 0.01). Most of both GD‐E and GD‐I neurons were activated by motilin (P < 0.05). The frequency and amplitude of gastric contractions significantly increased by administration of motilin in Arc with a dose dependent manner (P < 0.05–0.01). However, pretreatment with GM109 could abolish the responses of neurons and excitatory effect of gastric motility induced by motilin. Motilin immunoreactive neurons were increased in Arc via gastric distention (P < 0.05). Motilin/FG‐labeled neurons were detected in hypothalamus paraventricular nucleus (PVN). Conclusions & Inferences Our findings suggest that motilin neurons in Arc may accept peripheral somatosensory afferent inputs from gastric mechanoreceptors of the stomach, and also may acts as a stimulatory factor in Arc to regulate gastric motility via some inferior nucleus relay pathway. The results provide insight into the role of Arc in the control of digestion mediated via motilin.     

Neuronal expression of fos protein in the forebrain of diabetic rats

We sought to identify the areas that have altered neuronal activity within the hypothalamus of diabetic rats by mapping neuronal expression of c-fos protein (Fos) and Fos-related antigens. After a standard PAP immunocytochemical protocol, Fos-like immunoreactivity was observed in the paraventricular nucleus (PVN), supraoptic nucleus (SON), median preoptic area (MnPO), anterior hypothalamus (AH) and posterior hypothalamus (PH) of control (vehicle; n=6) and diabetic rats (Sprague-Dawley rats injected with STZ 65 mg/kg/ip 4 weeks prior to the experiment; n=6). Blood glucose levels were significantly elevated in the diabetic group (370+/-8 mg/dl) compared to control group (104+/-3 mg/dl). Diabetic rats had a significantly higher number of Fos-positive cells in PVN (2.5x), SON (7x) and MnPO (2x) compared to the control rats. However, diabetic rats had significantly fewer Fos-positive cells in the AH (0.3x) and no difference was observed in the PH between the diabetic and control rats. Despite the elevated number of Fos-positive cells in the diabetic rats, dehydration (water withdrawal for 24 h) or hypertonic challenge (1.5 ml of 0.1 M NaCl i.p. injection) produced a further increase in the number of Fos-positive cells in the PVN, SON and MnPO. Dehydration did not alter the number of Fos-positive cells in the AH or PH, but hypertonic challenge produced a significant increase in the Fos-positive cells in both the AH and PH of diabetic rats. This study demonstrates that: (1) there is increased basal neuronal activity in the PVN, SON and MnPO, a decrease in neuronal activity in the AH and no change in neuronal activity in the PH as indicated by Fos staining in diabetic rats; and (2) dehydration or hypertonic challenge produces a further increase in the number of Fos-positive cells in the PVN, SON, and MnPO which is comparable to control rats. These data support the conclusion that vasopressin producing neurons in the PVN and SON and autonomic areas within the lamina terminalis and hypothalamus are activated during diabetes and may contribute to the elevated levels of vasopressin and autonomic dysfunction during diabetes.     

Neuronal expression of Fos protein in the hypothalamus of rats with heart failure

We sought to identify the areas that have altered neuronal activity within the hypothalamus of rats with heart failure (HF) by mapping neuronal staining of c-Fos protein (Fos) 6-8 weeks following coronary artery ligation (HF group; n=17) or sham surgery (sham-operated control group, n=15). Fos-like immunoreactivity was observed in the paraventricular nucleus (PVN), supraoptic nucleus (SON), median preoptic nucleus (MnPO), anterior hypothalamus (AH) and posterior hypothalamus (PH) using a standard ABC immunocytochemical protocol. The rats in the HF group displayed infarcts averaging 34+/-2% of the outer circumference and 41+/-1% of the inner circumference of the left ventricular wall. Sham-operated control rats had no observable damage to the myocardium. Rats with chronic heart failure (n=5) but no manipulation (no surgery) had a similar number of Fos-staining cells in PVN SON, MnPO, AH and PH compared to sham-operated rats. Acute surgery for isolation of vagus nerves and anesthesia for 90 min increased the number of Fos positive cells in PVN, SON and MnPO of both sham-operated rats and rats with HF. Furthermore, rats with heart failure (n=5) had significantly higher number of Fos-staining cells in PVN (four times), SON (4.5 times) and MnPO (1.5 times) compared to sham-operated rats after acute surgery for isolation of the vagus. The number of Fos-staining cells remained unaltered in AH and PH in both groups of rats. However, in a third series of experiments vagotomy reduced the number of Fos-staining cells in the PVN, SON or MnPO of rats with HF (n=5) to those observed in sham-operated vagotomized rats. This study shows that: (1) there is augmented neuronal activity as indicated by increased number of Fos staining neurons in the PVN, SON and MnPO due to acute surgical stress in rats with HF, and (2) vagal afferents are responsible for the increased neuronal activity in PVN, SON and MnPO of rats with HF during acute surgical stress. These data support the conclusion that vasopressin producing neurons and autonomic areas within the hypothalamus influenced by vagal afferents are activated during HF and are sensitive to 'acute surgical stress' and may contribute to the elevated levels of vasopressin and sympatho-excitation commonly observed in heart failure.     

Increased nitric oxide synthase activity and expression in the hypothalamus of hindlimb unloaded rats

Upon return from spaceflight or resumption of normal posture after bed rest, individuals often exhibit cardiovascular deconditioning. Although the mechanisms responsible for cardiovascular deconditioning have yet to be fully elucidated, alterations within the central nervous system have been postulated to be involved. The paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the hypothalamus are important brain regions in control of sympathetic outflow and body fluid homeostasis. Nitric oxide (NO) modulates the activity of PVN and SON neurons, and alterations in NO transmission within these brain regions may contribute to symptoms of cardiovascular deconditioning. The purpose of the present study was to examine nitric oxide synthase (NOS) activity and expression in the PVN and SON of control and hindlimb unloaded (HU) rats, an animal model of cardiovascular deconditioning. The number of neurons exhibiting NOS activity as assessed by NADPH-diaphorase staining was significantly greater in the PVN but not SON of HU rats. Western blot analysis revealed that neuronal NOS (nNOS) but not endothelial NOS (eNOS) protein expression was higher in the PVN of HU rats. In the SON, there was a strong trend for an increase in nNOS (p=0.052) and a significant increase in eNOS expression in HU rats. Our results suggest that increased nNOS in the PVN contributes to autonomic and humoral alterations following cardiovascular deconditioning. In contrast, the functional significance of increases in nNOS and eNOS protein in the SON may be related to alterations in vasopressin release observed previously in HU rats.     

Visceral sensory inputs to the endocrine hypothalamus

Interoceptive feedback signals from the body are transmitted to hypothalamic neurons that control pituitary hormone release. This review article describes the organization of central neural pathways that convey ascending visceral sensory signals to endocrine neurons in the paraventricular (PVN) and supraoptic nuclei (SON) of the hypothalamus in rats. A special emphasis is placed on viscerosensory inputs to corticotropin releasing factor (CRF)-containing PVN neurons that drive the hypothalamic-pituitary-adrenal axis, and on inputs to magnocellular PVN and SON neurons that release vasopressin (AVP) or oxytocin (OT) from the posterior pituitary. The postnatal development of these ascending pathways also is considered.     

万拉法新对强迫游泳大鼠下丘脑c—fos和c—jun蛋白表达的影响

目的：探索急慢性给予新一代抗抑郁药万拉法新对大鼠下丘脑ｃ－ｆｏｓ和ｃ－ｊｕｎ蛋白表达的影响。方法 采用特性抗体的原位免疫细胞化学方法，在强迫游泳大鼠抑郁模型上，观察万拉法新急慢性给药对大鼠游泳不动时间和在脑核团ｃ－ｆｏｓ和ｃ－ｊｕｎ表达的影响；用图像分析技术对大鼠下丘脑室旁核和视上核内的ｆｏｓ和ｊｕｎ阳性细胞的相对切面面积比和平均目标灰度进行分析。     

万拉法新对强迫游泳大鼠下丘脑和海马c-fos及c-jun蛋白表达的下调作用

目的　探索新一代抗抑郁药万拉法新对大鼠下丘脑和海马内ｃｆｏｓ 和ｃｊｕｎ 蛋白表达的影响。方法　采用特异性抗体的原位免疫细胞化学方法,在强迫游泳大鼠抑郁模型上,观察万拉法新慢性给药（ 腹腔内注射每日１ 次,连续７ 次）对大鼠游泳不动时间和下丘脑及海马核团ｃｆｏｓ 和ｃｊｕｎ 表达的影响;用图像分析技术对大鼠下丘脑室旁核（ Ｐ Ｖ Ｎ） 、视上核（ Ｓ Ｏ Ｎ） 和海马齿状回（ Ｄ Ｇ） 内的ｆｏｓ 和ｊｕｎ 阳性细胞的相对切面面积比和平均目标灰度进行分析。结果　强迫游泳可使大鼠下丘脑和海马内多个核团的ｃｆｏｓ 和ｃｊｕｎ 蛋白表达水平增加,而万拉法新明显缩短了强迫游泳大鼠的不动时间。图像分析结果提示,万拉法新使强迫游泳大鼠下丘脑 Ｐ Ｖ Ｎ 和 Ｓ Ｏ Ｎ 及海马 Ｄ Ｇ 内ｆｏｓ 和ｊｕｎ 阳性细胞相对切面面积比明显降低（ Ｐ＜００５） ,而平均目标灰度显著增加（ Ｐ＜ ００１） 。结论　下丘脑 Ｐ Ｖ Ｎ、 Ｓ Ｏ Ｎ 和海马 Ｄ Ｇ 可能是介导抗抑郁药抑制大鼠绝望行为的重要中枢核团,ｆｏｓ 和ｊｕｎ 蛋白可能是抗抑郁药发挥受体后作用的传导物质。     

Evidence That IGF-I Acts as an Autocrine/Paracrine Growth Factor in the Magnocellular Neurosecretory System: Neuronal Synthesis and Induction of Axonal Sprouting

The ability of mature oxytocinergic (OT) and vasopressinergic (VP) neurons of the magnocellular neurosecretory system (MNS) to undergo axonal growth implies that one or more growth factors may be active in the adult MNS, yet little is known regarding their possible identity. One such potential factor is insulin-like growth factor I (IGF-I). We have examined the expression of IGF-I mRNA and IGF-I-immunoreactivity (IGF-I-ir) in the mature MNS and have also determined the in vivo response of OT and VP neurons to hypothalamic implants of IGF-I. In situ hybridization revealed moderate labeling of IGF-I mRNA in both the supraoptic (SON) and the paraventricular (PVN) nuclei of adult male rats. RT-PCR analysis confirmed the presence of authentic IGF-I mRNA in extracts of the basal hypothalamus. Faint IGF-I-ir was detected in scattered magnocellular neurons within both the PVN and the SON of normal rats, but IGF-I-ir was much more intense and the majority of MNS neurons including those in the accessory nuclei were immunoreactive in sections from rats given colchicine, as were some parvocellular neurons in the PVN. Confocal microscopy revealed that IGF-I-ir was present in both OT and VP neurons, but VP neurons contained the most intense IGF-I-ir. Finally, a dramatic growth response of OT but not of VP fibers was observed following implantation of polymer rods containing IGF-I into the hypothalamus. A dense OT fiber plexus grew along the cannula track and OT fibers invaded the leptomeninges ventral to the SON and encircled the rostral cerebral artery. To our knowledge this is the first demonstration of axonal sprouting by mature OT neurons in response to an identified growth factor and the first direct demonstration of sprouting in response to exogenous IGF-I in the adult CNS. These findings suggest that IGF-I is synthesized and transported by adult MNS neurons where it may act as an autocrine and/or paracrine growth factor.