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。     

Immunoautoradiographic determination of β1−G-globulin in the blood serum of patients with trophoblastic tumors

The results of determination of _1–G-globulin by immunoautoradiographic (IAR) and immunodiffusion (ID) methods in the blood serum of patients with trophoblastic tumors are compared. When negative results were obtained by the ID method, _1–G-globulin was found by means of the IAR method in seven of eight tests in chorionepithelioma of the uterus before treatment and in seven of 21 tests of the blood serum from patients of the same group after treatment. In the early stages of development of chorionepithelioma of the uterus (the state after hydatidiform mole, malignant hydatidiform mole) _1–G-globulin was found by the IAR method 4.5 times more frequently than by the ID method. This globulin was also found by the IAR method in testicular teratoblastoma with elements of chorionepithelioma. No -globulin could be found by the IAR method in the blood serum of other oncologic patients or donors.Department of Biochemistry, Problem Laboratory for Immunochemistry of Malignant and Embryonic Tissues, N. I. Pirogov Second Moscow Medical Institute. Laboratory of Immunochemistry of Tumors, N. F. Gamaleya Institute of Epidemiology and Microbiology, Academy of Medical Sciences of the USSR. Institute of Experimental and Clinical Oncology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR N. A. Kraevskii.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 80, No. 9, pp. 86–89, September, 1975.     

3,4-Methylenedioxymethamphetamine induces differential regulation of tryptophan hydroxylase 2 protein and mRNA levels in the rat dorsal raphe nucleus

Previous investigations with 3,4-methylenedioxymethamphetamine (MDMA) have suggested that administration of this drug results in a degeneration of 5-HT nerve terminals and subsequent alterations in 5-HT neurotransmission. However, only limited investigations have examined the effects of MDMA on the dorsal raphe nucleus. The present study was designed to assess the effect of MDMA on the rate-limiting enzyme in 5-HT biosynthesis, tryptophan hydroxylase (TPH), by measuring TPH2 protein and mRNA levels in rat dorsal raphe (DR) nucleus. Rats were administered MDMA (20 mg/kg, s.c.) or saline twice daily for 4 days and killed 14 days later. Tissue sections of the DR were processed for quantitative immunoautoradiography and in situ hybridization histochemistry for measurements of the levels of TPH2-immunoreactivity (IR) and TPH2 mRNA. To assess 5-HT axon terminal integrity after MDMA treatment, the density of 5-HT transporter (SERT) binding sites was measured by quantitative autoradiography using [125I]RTI-55 ((-)-2beta-carbomethoxy-3 beta-(4-iodophenyl) tropane) ((125)I-RTI-55) as a ligand. TPH2-IR levels were significantly decreased by 45% in the mid DR and by 40% in the caudal DR in the MDMA-treated rats compared with saline-injected rats. In contrast, TPH2 mRNA levels were significantly increased by 24% in the mid DR and by 12% in the caudal DR. MDMA treatment significantly decreased (125)I-RTI-55 labeled SERT binding sites in the striatum, nucleus accumbens and cingulate cortex demonstrating a loss of 5-HT terminals. The increase in TPH2 mRNA levels in both the mid DR and caudal DR of MDMA-treated rats may reflect a compensatory mechanism in the injured 5-HT neurons to increase TPH2 protein synthesis. Taken together, our results suggest that a serious defect occurs in the biosynthesis of TPH2 in the DR following MDMA administration.     

人脑标本不同区域多巴胺转运体分布的免疫放射自显影研究

目的 定量分析人脑标本不同区域多巴胺转运体(DAT)的免疫反应强度,为神经影像检查DAT变化的参照区选择提供依据.方法 取自8例男性尸脑标本的脑组织块经石蜡包埋切片后,以免疫放射自显影显示黑质、壳及尾状核、扣带回、额叶、枕叶和小脑皮质的DAT免疫反应强度.结果 所观察的脑区中,DAT免疫反应强标记主要分布在黑质、尾状核及壳,小脑皮质标记最弱.定量分析发现,小脑皮质的DAT免疫反应强度分别为额叶、扣带回及枕叶的1/3.50、1/3.72、1/1.28,仅为黑质、尾状核、壳的1/8.33、1/11.67、1/8.56.结论 小脑皮质在所检脑区中DAT含量最低,可作为神经影像检查DAT变化的参照区.     

帕金森症患者脑标本5羟色胺转运体的表达

目的观察帕金森症(PD)患者脑标本5羟色胺转运体(SERT)的表达。方法以免疫放射自显影显示SERT在脑标本的分布。结果与健康组比,PD人脑标本中缝背核、黑质以及纹状体的SERT标记信号呈不同程度降低。定量分析发现SERT标记强度在壳、尾状核、黑质以及腹侧被盖区分别比健康组降低25.9%、31.1%、27.2%和24.7%,有显著差异;在中缝背核的4个亚区中,中缝背核腹侧部、背侧部、尾侧部及束间部分别比健康组显著减少了38.9%、37.3%、16.5%和37.0%;中缝正中核SERT标记强度未见显著降低。结论5羟色胺能体系的功能障碍可能参与了帕金森症的发生。     

Increased tryptophan hydroxylase immunoreactivity in the dorsal raphe nucleus of alcohol-dependent, depressed suicide subjects is restricted to the dorsal subnucleus

Considerable evidence suggests that alcoholics with co-occurring depressive disorder are at greater risk for developing psychosocial problems particularly suicidal behavior. Moreover, dysfunction in serotonin (5-HT) neurotransmission has been implicated in depression, suicide and alcoholism. In the present study, we measured the levels of tryptophan hydroxylase (TPH), the main synthetic enzyme of 5-HT synthesis, in specific nuclei of the dorsal raphe (DR) in depressed suicide victims with alcohol dependence and matched psychiatrically normal controls. TPH immunoreactivity (IR) was quantified in frozen tissue sections containing the DR from 8 suicide victims with a diagnosis of major depression and alcohol dependence, and 8 psychiatrically normal control subjects by using immunoautoradiographic methods. We found that the levels of TPH-IR were significantly increased by 46% in the dorsal subnucleus of the DR in depressed suicide victims with alcohol dependence when compared with controls. In contrast, TPH-IR levels did not significantly differ in the other DR subnuclei between depressed, alcoholic suicide subjects, and controls. Our results indicate that abnormalities in 5-HT biosynthesis in the brain of depressed alcoholic suicide subjects are restricted within distinct regions of the DR.     

Circadian tryptophan hydroxylase levels and serotonin release in the suprachiasmatic nucleus of the rat

Serotonin (5-HT) plays an important role in the regulation of the time-keeping system in rodents. In the present study, we have investigated the interplay between the rhythms of 5-HT synthesis and release in the suprachiasmatic nuclei (SCN) of the rat. The quantitative distribution of tryptophan hydroxylase (TpH) protein was used as an index of 5-HT synthesis, in perikarya and terminals areas. In the raphe medianus, the maximal levels of TpH was reached in the early daytime period, followed by a decrease before the onset of darkness. Conversely, in the axon terminals of the SCN the highest levels of TpH were found before the onset of the dark-period. Furthermore, TpH amount in SCN displays variations depending on the anatomical area of the SCN. Extracellular 5-HT peaked at the beginning of the night, as evidenced by in vivo microdialysis in the SCN. The 5-HT metabolite, 5-HIAA, presented a similar pattern, but the acrophase occurred in the middle of the dark period. These results suggest that TpH is transported from the soma to the nerve terminals in which 5-HT is synthesized during daytime. This would fill the intracellular stores of 5-HT to provide for its nocturnal release.     

尸脑不同区域5-羟色胺转运体分布的免疫放射自显影

目的：定量分析人脑标本不同区域5-羟色胺转运体(SERT)的免疫反应强度,为筛选适于神经影像检查SERT变化的最佳参照区提供神经解剖学依据。方法：利用免疫放射自显影的方法显示不同脑区SERT免疫反应强度的差异。结果：在所观察的脑区中,SERT免疫反应强标记信号主要分布在脑干的中缝核区;小脑皮质与胼胝体区相近、标记最弱。定量分析发现,小脑皮质的SERT免疫反应强度分别为额叶、枕叶及胼胝体的1/ 1．83、1/2．17、1/0．67,仅占中缝背核、黑质、尾状核、壳的1/49．83、1/28．83、1/5．12、1/4．67。结论：小脑皮质在所检脑区中SERT含量最低,如果放射性配基选择适当,不失为较为理想的参照区。     

酗酒与扣带回前部膝周皮质5-羟色胺转运体的表达

目的观察酗酒者脑标本扣带回前部膝周皮质5-羟色胺转运体（SERT）的表达变化.方法以免疫放射自显影显示SERT在扣带回前部膝周皮质的免疫反应强度.结果健康者脑标本SERT标记信号在扣带回主要分布于胼胝体前部膝周皮质处;酗酒者脑标本,其正常分布于扣带回前部膝周皮质的SERT标记信号减弱;定量分析发现SERT免疫反应强度在酗酒者扣带回前部膝周皮质比健康者降低20.89%（P〈0.01）.结论酗酒者扣带回前部膝周皮质5-羟色胺转运体表达降低.