经鼻给予丙酸睾丸酮增加大鼠中脑5羟色胺能神经元的表达

目的:观察经鼻给予丙酸睾丸酮(TP)后大鼠中缝背核色氨酸羟化酶(TPH)及中缝背核、尾壳核与伏核5羟色胺(5-HT)和5羟色胺转运体(SERT)表达的改变.方法:对正常成年雄性及去势大鼠经鼻给予TP 21 d,利用免疫组织化学观察给药后大鼠中缝背核TPH及巾缝背核、尾壳核与伏核5-HT和SERT的免疫反应强度变化.结果:大鼠去势处理降低中缝背核TPH及中缝背核、尾壳核与伏核5-HT和SERT的表达;去势大鼠经鼻给予TP则可提高巾缝背核TPH及巾缝背核、尾壳核与伏核5-HT和SERT的表达,但未达到假手术水平;正常大鼠鼻腔给予TP后,中缝背核TPH及中缝背核、尾壳核与伏核5-HT和SERT的表达也显著增加.结论:经鼻给予TP增加大鼠中缝背核TPH及中缝背核、尾壳核与伏核5-HT和SERT的表达,为经鼻给予TP辅助治疗衰老过程中出现的运动相关行为障碍及抑郁症状提供实验依据.     

大鼠多重脑震荡后脑内TPH表达变化

目的:探讨多重脑震荡(multiple cerebral concussion,MCC)后脑内5-HT能神经元内色氨酸羟化酶(tryptophan hydroxylase,TPH)含量的变化。方法:42只雄性大鼠随即分为7组,每组6只,一组为对照组,其余的大鼠用金属单摆式机械打击装置复制MCC大鼠模型,伤后分1~24 d不同时段的6个损伤组,用免疫组化技术和图像分析方法观察基底前脑及脑干5-HT能神经元内TPH含量的变化。结果:多重脑震荡后2~8 d上述脑区TPH免疫阳性表达升高(P<0.05),伤后24 d趋于正常(P>0.05)。结论:多重脑震荡后5-HT神经元TPH表达增强,可能与脑损伤后神经元的应激反应有关。     

大鼠脑干中缝核群向额前皮质的传入投射──HRP法研究

本实验用ＨＲＰ法研究了２７只大鼠脑干中缝核群向额前皮质的传入联系。结果如下：向额前皮质各区泳注ＨＲＰ后，标记细胞出现于上位脑干的中缝核，即吻侧、尾侧线形核，中缝背核，正中中缝核；下位脑干的中缝核中，除中缝苍白核外，中缝桥核、中缝大核、中缝隐核中也见到标记细胞。各中缝核中，以中缝背核标记为最多，其次是正中中缝核、中缝桥核和中缝大核，较少的是中缝隐核，吻、尾侧线形核．标记细胞大部分为中、小型，偶见大型，形态为多极形、梭形或三角形．另外，发现中缝核向额前皮质不同区域投射的细胞数量不同，正中中缝核、中缝桥核和中缝大校主要投射到额前皮质的内侧部分、而中缝背核，吻、尾侧线形核主要投射到额前皮质的外侧部分．     

大鼠脑干5-羟色胺神经元的分布——免疫细胞化学研究和定量分析

应用免疫细胞化学卵白素-生物素-过氧化物酶复合体(Avidin-Biotin-peroxidase Complex, ABC)法研究了大鼠脑干含5-羟色胺(5-Hydroxytryptamine,5-HT)的神经元的分布。证实5-HT神经元广泛分布于中缝核群和网状结构。在延髓表面弓状细胞群、极后区、蓝斑复合体和脚间核中也含5-HT神经元。定量分析表明:①5-HT神经元在脑干各部的比例约为:中脑61％,延髓31％,脑桥8％;②中缝核群内5-HT神经元约占脑干5-HT细胞总数的60％,中缝以外约占40％;③5-HT细胞在各核的分布比例为:中缝苍白核6.15％,中缝隐核5.77％,中缝大核5.15％,中缝桥核2.09％,中央上核3.44％,中缝背核35.82％,线形头侧核1.76％,延髓网状结构13.99％,脑桥网状结构和第Ⅳ脑室室底灰质5.40％,中脑网状结构20.42％。本文对中缝各核的细胞密度和5-HT细胞密度进行了抽样分析,结果表明:含5-HT细胞较高的核团有:中缝苍白核56.36％,中缝隐核48.40％,中缝背核44.10％;其次为中央上核33.38％,中缝大核25.77％;线形头侧核和中缝桥含5-HT细胞较低,分别为18.19％和17.37％。     

大鼠脑干中缝核群向额前皮的传入投射—HRP法研究

本实验用ＨＲＰ法研究了２７只大鼠脑干中缝群向额前皮质的传入联系。结果如下：向额前皮质各区泳注ＨＲＰ后，标记细胞出现于位脑干的中缝核，却吻侧，尾侧线形核，即吻侧，尾侧线形核，中缝背核，正中中缝核；下位脑干的中缝核，除中缝苍白核外，中缝桥核，中缝隐核中也见到标记细胞。各中缝核中，以中缝背核标记为最多，其次是正中中缝核，中缝桥和中缝大核，较少的是中缝隐核，吻，尾侧线形核。标记细胞大部分为中，小型，偶见大     

左旋多巴对大鼠中脑5羟色胺能神经元的影响

目的:观察左旋多巴对大鼠脑内5羟色胺(5-HT)能神经元的影响.方法:左旋多巴大鼠灌胃,以免疫细胞化学和流式细胞术显示5-HT及色氨酸羟化酶(TPH)免疫反应物质或含量的变化.结果:免疫细胞化学显示左旋多巴组大鼠中缝背核5-HT能神经元细胞直径明显小于对照组;中缝背核5-HT和TPH免疫反应物质灰度值比对照组分别增高了7.72%和16.57%.流式细胞术显示左旋多巴组5-HT的表达量比对照组减少了18.45%,TPH表达量比对照组减少了19.90%.结论:左旋多巴降低脑内5-HT能神经元5-HT和TPH的表达.     

5-羟色胺转运体在酗酒人脑干头侧中缝核群的表达

目的:观察酗酒人脑标本脑干头侧中缝核群5-羟色胺转运体(SERT)的表达变化。方法:应用免疫放射自显影的方法,显示SERT免疫反应强度在酗酒人脑标本脑干头侧中缝核群的变化,并与健康人脑标本比较。结果:健康组SERT免疫反应强标记信号在脑桥头侧和中脑主要集中分布在与中缝核群相同的区域。在酗酒人脑标本,正常分布于脑干头侧中缝核群的SERT免疫反应标记信号减弱;中缝正中核、中缝背核尾侧部、中缝背核束间部、中缝背核腹侧部、中缝背核背侧部的SERT免疫反应含量强度与健康组相应区域比较显著降低。结论:酗酒者头侧中缝核群SERT蛋白表达降低。     

促性腺激素释放激素类似物对大鼠中缝核簇5-HT样阳性物质表达的影响

研究促性腺激素释放激素类似物 ( Gn RH-A)对大鼠中缝核簇 5 -HT样阳性物质表达的影响 ,采用酶联免疫吸附试验测定血清激素水平 ,用免疫组织化学方法和图像分析技术观察大鼠中缝核簇 5 -HT样阳性物质的表达。结果证明 :( 1) Gn RH-A组大鼠血清 17β-雌二醇 ( E2 )、LH及 FSH水平较正常对照组下降 ,差异显著 ( P<0 .0 5 ) ;与去卵巢组 ( OVX)比较 ,E2 相似 ,差异不显著 ( P>0 .0 5 ) ,但 L H、F SH较低 ( P<0 .0 5 ) ;与 Gn RH-A+E2 组比较 E2 浓度较低 ,差异显著 ( P<0 .0 5 ) ,L H、FSH相似 ( P>0 .0 5 )。( 2 ) 5 -HT样阳性物质在大鼠中缝背核 ,中缝正中核表达较多 ,Gn RH-A组大鼠中缝背核 ,中缝正中核 5 -HT样阳性细胞数及光密度值都低于正常对照组 ( P<0 .0 5 ) ,与去卵巢组相似 ( P>0 .0 5 )。 ( 3 ) Gn RH-A、17β-雌二醇联合用药后 ,大鼠中缝背核 ,中缝正中核 5 -HT样阳性细胞数及光密度值都与正常对照组相似 ,无显著差异 ( P>0 .0 5 )。结论 :Gn RH-A可改变大鼠中缝背核 ,中缝正中核 5 -HT样阳性物质表达 ,从而影响其神经元的功能 ,此点可能与其副作用类似绝经综合征有关。     

大鼠脑干至脊髓5-羟色胺投射纤维的起源——免疫细胞化学和酶组织化学双重标记法

本文应用 HRP 逆行追踪与免疫细胞化学相结合的双重标记技术,研究了大鼠脑干至脊髓5-羟色胺(5-HT)投射纤维的起源,并对中缝核群和网状结构内5-HT 阳性细胞、HRP 标记细胞和5-HT-HRP 双重标记细胞进行了数量分析。结果表明,1.在延髓、脑桥尾侧部,5-HT-HRP双重标记细胞约占5-HT 阳性细胞的55%;占 HRP 标记细胞的45%。中脑仅有极少数5-HT-HRP双重标记细胞。2.脑干至脊髓5-HT 下行投射,主要起源于中缝苍白核、中缝隐核、中缝大核和延髓浅表弓状纤维区,所含双重标记细胞约占双重标记细胞总数的68%。3.浅表弓状纤维区、舌下神经根间核、中缝苍白核和中缝隐核主要为5-HT 下行投射;中缝大核及周围网状结构主要为非5-HT 下行投射。     

多重脑震荡大鼠5-羟色胺能神经纤维变化

目的:研究多重脑震荡(MCC)与大鼠认知记忆相关脑区5-羟色胺(5-HT)能神经纤维变化的规律,以探讨MCC大鼠认知行为障碍的神经生物学基础。方法:应用自制单摆式机械打击装置构建MCC大鼠模型,免疫组织化学及半定量方法研究MCC后大鼠5-HT能神经纤维的变化。结果:前额叶皮质、中隔区、丘脑、海马CA1和CA3区5-HT能神经纤维免疫反应阳性物在伤后2d组反应达高峰,杏仁体、海马CA2和CA4区在伤后4d组免疫反应了阳性最强;顶叶皮质、梨状皮质及伏隔核内侧在伤后8d组反应最强。5-HT纤维密度在中隔区和伏隔核内侧以伤后2d最高,杏仁体区以伤后1d最高,大脑皮质和丘脑5-HT纤维密度在伤后各损伤组与对照组相比无显著性差异。结论:MCC可引起与认知功能有关脑区的5-HT表达增高,5-HT的高表达可能由脑损伤后神经元过度兴奋所引起的神经递质紊乱造成,而这种紊乱可能影响大鼠的认知功能。     

大鼠孤束核内5－羟色胺能纤维的来源──HRP逆行追踪与5－羟色胺免疫组织化学双标记洁研究

用ＨＲＰ注入孤束核逆行追踪和５－羟色胺（５－ＨＴ）免疫组织化学相结合的双标记法，观察大鼠孤束核内的５－ＨＴ能纤维和终末的来源。结果在脑干内见到许多ＨＲＰ单标、５－ＨＴ单标和ＨＲＰ／５－ＨＴ双标细胞，其中ＨＲＰ／５－ＨＴ双标细胞主要分布于脑桥被盖核（２６．５７％）、脑桥网状核（２４．１９％）、中缝大核（２１．１７％），其次为中缝隐核（１２．７４％）、中缝苍白核（７．７８％），少数见于中缝背核、中脑导水管周围灰质和中缝脑桥核等处。而在结状神经节内仅见到ＨＲＰ单标细胞，未见到５－ＨＴ单标和ＨＲＰ／５－ＨＴ双标细胞。以上结果表明，大鼠孤束核的５－ＨＴ能纤维和终末主要来源于脑桥与延髓的５－ＨＴ神经元的投射。本研究提示脑桥与延髓内上述核团的５－ＨＴ神经元通过向孤束核的直接投射参与孤束核内脏功能的调控。     

Nuclear organization of the serotonergic system in the brain of the rock cavy (Kerodon rupestris)

Serotonin, or 5-hydroxytryptamine (5-HT), is a substance found in many tissues of the body, including as a neurotransmitter in the nervous system, where it can exert different post-synaptic actions. Inside the neuro-axis, 5-HT neurons are almost entirely restricted to the raphe nuclei of the brainstem. As such, 5-HT-immunoreactivity has been considered a marker of the raphe nuclei, which are located in the brainstem, at or near the midline. The present study investigated distribution of serotonergic neurons in the brain of the rock cavy (Kerodon rupestris), a rodent species inhabiting the Brazilian Northeast. The cytoarchitectonic location of serotonergic neurons was established through a series of 5-HT immunostained sections, compared with diagrams obtained from adjacent coronal and sagittal sections stained by the Nissl method. The following nuclei were defined: the rostral group, consisting of rostral linear raphe, caudal linear raphe, median and paramedian raphe, dorsal raphe, and pontine raphe nuclei, and the caudal group composed of raphe magnus, raphe pallidus and raphe obscurus nuclei. Other serotonergic neuronal clusters, such as the supralemniscal group and the rostral and caudal ventrolateral medulla oblongata clusters, were found outside the midline. Rare 5-HT-producing neurons were identified in the lateral parabrachial nucleus and in the pontine reticular formation, mostly along fibers of the lateral lemniscus. Despite exhibiting some specializations, the picture outlined for serotonergic groups in the rock cavy brain is comparable to that described for other mammalian species.     

The projection from nucleus raphe magnus and other brainstem nuclei to the spinal cord in the rat: a study using the HRP blue-reaction

Horseradish peroxidase injections, or solid HRP placements, were made into the dorsolateral quadrant of the spinal cord in ten adult rats, processed according to the blue-reaction (benzidine dihydrochloride) protocol [6]. When the interventions involved the dorsal lateral funiculus (DLF) HRP-labelled somata were observed primarily in the ipsilateral nucleus raphe magnus (NRM), with an occasional cell in nucleus raphe obscurus (NRO) and pallidus (NRP). Other brainstem raphe nuclei consistently lacked labelled neurons. The red nucleus and paralemniscal reticular formation of the rostal pons also contained appreciable numbers of HRP back-filled perikarya. The direct NRM-spinal projection in the rat, involved in the modulation of pain transmission in the spinal cord dorsal horn, originates primarily from the expanded region of the nucleus in the rostralmost medulla.     

Brainstem projections from the lateral hypothalamic area in the rat, as studied with autoradiography

Descending projections from the lateral hypothalamic area to the brainstem were studied, using [3H]-amino acid autoradiography, in the rat. Two main ipsilateral paths were reorganized. One is the periventricular fiber system projecting to the midbrain central gray. The other is a fiber system which eventually descends the central tegmental field, projecting strongly to the dorsal raphe nucleus, medial and lateral parabrachial nuclei, nucleus reticularis parvocellularis, solitary nuclei and dorsal motor nucleus of the vagus nerve. Sparse projections were observed to the nuclei raphe magnus, obscurus and pallidus, group B3 (or the ventrolateral subpial group) and spinal trigeminal nucleus.     

5-HT样阳性结构在新生儿脑干内的分布

用免疫组织化学方法(PAP法,ABC法)对5-HT样结构在生后2天的新生儿脑干内的分布进行了观察。发现脑干内的5-HT样阳性胞体可分为延髓中缝群、延髓外侧群、桥脑中脑中缝群和桥脑中脑外侧群。延髓中缝群分别位于中缝苍白核、中缝隐核和中缝大核。延髓外侧群位于网状结构,又可分为腹侧亚群和背侧亚群,前者位于下橄榄核与锥体之间,自内侧向外侧伸展;后者在下橄揽核的背侧,自背内侧向腹外侧斜行排列。桥脑中脑中缝群包括中缝桥核、中央上核、中缝背核、吻侧线状核以及第四脑室底灰质和中脑中央灰质。桥脑中脑外侧群位于桥脑以及中脑尾段的网状结构内,也可分为腹侧亚群和背侧亚群,腹侧亚群沿内侧丘系分布;背侧亚群位于被盖背侧,自背内侧向腹外侧斜行分布。本文观察到粗有膨体、粗无膨体、细无膨体、细有膨体以及颗粒线状等几种纤维。5-HT样终末有的与非5-HT样胞体或树突接触,有的与5-HT样胞体或树突接触,有的伸至第四脑室室管膜,有的与脑内小血管接触。此外也见到5-HT样胞体或树突与脑内小血管接触。5-HT样纤维或终末在三叉神经脊束核、孤束核、面神经核、三叉神经运动核以及网状结构外侧部比较密集,而黑南内则很稀少。     

Evidence for colocalization of substance P and 5-hydroxytryptamine in spinally projecting neurons from the cat medulla oblongata

Substance P (SP)- and 5-hydroxytryptamine (5-HT)-like immunoreactivities were localized in bulbospinal neurons of the raphe nuclei and ventrolateral medulla (VLM). In raphe pallidus and raphe obscurus virtually all of the spinally projecting neurons contained SP and/or 5-HT. Furthermore, SP and 5-HT were colocalized in half of these spinal-raphe neurons. In raphe magnus few spinally projecting neurons contained either SP or 5-HT. Half of the bulbospinal neurons in the caudal VLM contained SP and/or 5-HT and in 50% of these SP and 5-HT were colocalized. However, no SP-containing neurons in the rostral VLM projected to the spinal cord.     

A lectin horseradish peroxidase study of the origin of ascending fibers in the medial forebrain bundle of the rat. The lower brainstem

The origins of projections within the medial forebrain bundle from the lower brainstem were examined with the horseradish peroxidase technique. Labeled cells were found in at least 15 lower brainstem nuclei following injections of a conjugate or horseradish peroxidase and wheat germ agglutinin at various levels of the medial forebrain bundle. Dense labeling was observed in the following cell groups (from caudal to rostral): A1 (above the lateral reticular nucleus); A2 (mainly within the nucleus of the solitary tract); a distinct group of cell trailing ventrolaterally from the medial longitudinal fasciculus at the level of the rostral pole of the inferior olive; raphe magnus; nucleus incertus; dorsolateral tegmental nucleus (of Castaldi); locus coeruleus; nucleus subcoeruleus; caudal part of the dorsal (lateral) parabrachial nucleus; and raphe pontis. Distinct but light labeling was seen in raphe pallidus and obscurus, nucleus prepositus hypoglossi, nucleus gigantocellularis pars ventralis, and the ventral (medial) parabrachial nucleus. Sparse labeling was observed throughout the medullary and caudal pontine reticular formation. Several lower brainstem nuclei were found to send strong projections along the medial forebrain bundle to very anterior levels of the forebrain. They were: A1, A2, raphe magnus (rostral part), nucleus incertus, dorsolateral tegmental nucleus, raphe pontis and locus coeruleus. With the exception of the locus coeruleus, attention has only recently been directed to the ascending projections of most of the nuclei mentioned above. Evidence was reviewed indicating that fibers from lower brainstem nuclei with ascending medial forebrain bundle projections distribute to widespread regions of the forebrain.It is concluded from the present findings that several medullary cell groups are capable of exerting a direct effect on the forebrain and that the medial forebrain bundle is the major ascending link between the lower brainstem and the forebrain.     

Vardenafil Increases Cell Proliferation in the Dentate Gyrus through Enhancement of Serotonin Expression in the Rat Dorsal Raphe

This study was conducted to evaluate the effects of vardenafil (Levitra), a phosphodiesterase-5 (PDE-5) inhibitor, on cell proliferation in the hippocampal dentate gyrus and on 5-hyroxytryptamine (5-HT, serotonin) synthesis and tryptophan hydroxylase (TPH) expression in the rat dorsal raphe nucleus. Male Sprague-Dawley rats were divided into 6 groups (n=5 in each group): a control group, a 0.5 mg/kg-1 day vardenafil-treated group, a 1 mg/kg-1 day vardenafil-treated group, a 2 mg/kg-1 day vardenafil-treated group, a 1 mg/kg-3 day vardenafil-treated group, and a 1 mg/kg-7 day vardenafil-treated group. 5-bromo-2''-deoxyuridine (BrdU) immunohistochemistry was then performed to evaluate cell proliferation in the dentate gyrus. In addition, 5-HT and TPH immunohistochemistry was conducted to evaluate serotonin expression in the dorsal raphe. The results revealed that treatment with vardenafil increased cell proliferation in the dentate gyrus and enhanced 5-HT synthesis and TPH expression in the dorsal raphe in a dose- and duration-dependent manner. The findings demonstrate that the increasing effect of vardenafil on cell proliferation is closely associated with the enhancing effect of vardenafil on serotonin expression under normal conditions.