共查询到20条相似文献，搜索用时 31 毫秒
1.
Grafts of fetal dopamine neurons survive and improve motor function in Parkinson's disease 总被引：28，自引：0，他引：28
O Lindvall P Brundin H Widner S Rehncrona B Gustavii R Frackowiak K L Leenders G Sawle J C Rothwell C D Marsden 《Science (New York, N.Y.)》1990,247(4942):574-577
Neural transplantation can restore striatal dopaminergic neurotransmission in animal models of Parkinson's disease. It has now been shown that mesencephalic dopamine neurons, obtained from human fetuses of 8 to 9 weeks gestational age, can survive in the human brain and produce marked and sustained symptomatic relief in a patient severely affected with idiopathic Parkinson's disease. The grafts, which were implanted unilaterally into the putamen by stereotactic surgery, restored dopamine synthesis and storage in the grafted area, as assessed by positron emission tomography with 6-L-[18F]fluorodopa. This neurochemical change was accompanied by a therapeutically significant reduction in the patient's severe rigidity and bradykinesia and a marked diminuation of the fluctuations in the patient's condition during optimum medication (the "on-off" phenomenon). The clinical improvement was most marked on the side contralateral to the transplant. 相似文献
2.
Dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine in mice 总被引：35，自引：0，他引：35
1-Methyl-4-phenyl-1,2,5,6- tetrahydropyri dine ( MPTP ) is known to cause an irreversible destruction of the dopaminergic nigrostriatal pathway and symptoms of parkinsonism in humans and in monkeys. However, MPTP has been reported to act only minimally or not at all in several other animal species. When MPTP (30 milligrams per kilogram of body weight) was administered parenterally to mice, a decrease in concentrations of neostriatal dopamine and its metabolites, a decrease in the capacity of neostriatal synaptosomal preparations to accumulate [3H]dopamine, and a disappearance of nerve cells in the zona compacta of the substantia nigra were observed. In contrast, MPTP administration had no effect on neostriatal concentrations of serotonin and its metabolites. MPTP administration thus results in biochemical and histological changes in mice similar to those reported in humans and monkeys and similar to those seen in Parkinson's disease in humans. The mouse should prove to be a useful small animal with which to study the mode of action of MPTP . 相似文献
3.
D1 and D2 dopamine receptor-regulated gene expression of striatonigral and striatopallidal neurons 总被引：63，自引：0，他引：63
C R Gerfen T M Engber L C Mahan Z Susel T N Chase F J Monsma D R Sibley 《Science (New York, N.Y.)》1990,250(4986):1429-1432
The striatum, which is the major component of the basal ganglia in the brain, is regulated in part by dopaminergic input from the substantia nigra. Severe movement disorders result from the loss of striatal dopamine in patients with Parkinson's disease. Rats with lesions of the nigrostriatal dopamine pathway caused by 6-hydroxydopamine (6-OHDA) serve as a model for Parkinson's disease and show alterations in gene expression in the two major output systems of the striatum to the globus pallidus and substantia nigra. Striatopallidal neurons show a 6-OHDA-induced elevation in their specific expression of messenger RNAs (mRNAs) encoding the D2 dopamine receptor and enkephalin, which is reversed by subsequent continuous treatment with the D2 agonist quinpirole. Conversely, striatonigral neurons show a 6-OHDA-induced reduction in their specific expression of mRNAs encoding the D1 dopamine receptor and substance P, which is reversed by subsequent daily injections of the D1 agonist SKF-38393. This treatment also increases dynorphin mRNA in striatonigral neurons. Thus, the differential effects of dopamine on striatonigral and striatopallidal neurons are mediated by their specific expression of D1 and D2 dopamine receptor subtypes, respectively. 相似文献
4.
T Yamaguchi T Nagatsu T Sugimoto S Matsuura T Kondo R Iizuka H Narabayashi 《Science (New York, N.Y.)》1983,219(4580):75-77
After administration of tyrosine, total concentration of biopterin, the cofactor for tyrosine hydroxylase, was increased in the striatum, adrenal glands, and serum of rats, and in the serum of humans. Serum biopterin is lower in patients with Parkinson's disease than in normal controls. After oral administration of tyrosine, the increase in serum biopterin concentration was smaller in patients with Parkinson's disease (less than twofold) than in healthy controls (three-to sevenfold). These results suggest that tyrosine may have a regulatory role in biopterin biosynthesis and that patients with Parkinson's disease may have some abnormality in the regulation of biopterin biosynthesis. 相似文献
5.
The dorsal striatum plays a role in consummatory food reward, and striatal dopamine receptors are reduced in obese individuals, relative to lean individuals, which suggests that the striatum and dopaminergic signaling in the striatum may contribute to the development of obesity. Thus, we tested whether striatal activation in response to food intake is related to current and future increases in body mass and whether these relations are moderated by the presence of the A1 allele of the TaqIA restriction fragment length polymorphism, which is associated with dopamine D2 receptor (DRD2) gene binding in the striatum and compromised striatal dopamine signaling. Cross-sectional and prospective data from two functional magnetic resonance imaging studies support these hypotheses, which implies that individuals may overeat to compensate for a hypofunctioning dorsal striatum, particularly those with genetic polymorphisms thought to attenuate dopamine signaling in this region. 相似文献
6.
Neural transplantation: a call for patience rather than patients 总被引：3，自引：0，他引：3
Research into embryonic cell grafting in human subjects suffering from Parkinson's disease should not repeat the mistakes made by adrenal autograft investigators, who operated on far more humans than on nonhuman primates because of a single unconfirmed report of dramatic improvement in two Mexican patients. Citing extensive data from experimental transplants conducted as early as 1944, the authors argue that, until a sufficient number of animal studies have been performed to answer many crucial questions about human fetal tissue transplants, researchers should refrain from experimenting on human patients. 相似文献
7.
用Ｗｉｓｔａｒ大鼠脑新皮质组织移植于同种幼鼠相应区域，术后分别于７天，１５天，３０天，６０天、１５０天应用光镜，电镜、免疫组织化学及酶组织化学的方法，观察移植物生长与发育成熟的形态特征，并应用辣极过氧化物酶追踪技术观察移植物和受体脑之间的神经纤维联系。结果表明：大部分移植物内的神经元不仅能存活，且能生长发育成熟为和受体脑相似的正常神经元，部分存活的移植物和受体脑之间可形成程度不同的神经纤维联系。 相似文献
8.
At synapses between cortical pyramidal neurons and principal striatal medium spiny neurons (MSNs), postsynaptic D1 and D2 dopamine (DA) receptors are postulated to be necessary for the induction of long-term potentiation and depression, respectively-forms of plasticity thought to underlie associative learning. Because these receptors are restricted to two distinct MSN populations, this postulate demands that synaptic plasticity be unidirectional in each cell type. Using brain slices from DA receptor transgenic mice, we show that this is not the case. Rather, DA plays complementary roles in these two types of MSN to ensure that synaptic plasticity is bidirectional and Hebbian. In models of Parkinson's disease, this system is thrown out of balance, leading to unidirectional changes in plasticity that could underlie network pathology and symptoms. 相似文献
9.
Dissociated cell suspensions, prepared from the substantia nigra and septal regions of rat embryos, can be grafted to the depths of the caudate-putamen and hippocampus of aged rats. The grafts were rich in dopamine-containing and acetylcholinesterase-positive neurons and had produced extensive new dopaminergic and cholinergic terminal networks in the host neostriatum and hippocampus, respectively. The intrastriatal dopaminergic grafts were associated with a significant improvement in motor coordination in the aged rats. This result suggests that the intracerebral grafting technique may provide a new tool for exploring the role of dopaminergic and cholinergic deficits in the neurological and behavioral impairments associated with aging. 相似文献
10.
Involvement of adenosine 3',5'-monophosphate in the activation of tyrosine hydroxylase elicited by drugs 总被引：12，自引：0，他引：12
Immediately after the injection of reserpine (16 micromoles per kilogram, intraperitoneally), aminophylline (200 micromoles per kilogram, intraperitoneally), and carbamylcholine (8.2 micromoles per kilogram, intraperitoneally), the concentration of adenosine 3',5'-monophosphate in adrenal medulla of rats is increased severalfold. The three drugs also cause a delayed increase of medullary tyrosine hydroxylase activity. Our results are consistent with the view that an increase of medullary adenosine 3',5'-monophosphate concentration is involved in the drug-induced increase of tyrosine hydroxylase activity in adrenal medulla. Experiments with tyramine (130 micromoles per kilogram, intraperitoneally) suggest that the increase of tyrosine hydroxylase activity and of adenosine 3',5'-monophosphate concentrations is independent of an increase in adrenal catecholamine turnover rate. 相似文献
11.
Normalization of spiroperidol binding in the denervated rat striatum by homologous grafts of substantia nigra 总被引：3，自引：0，他引：3
W J Freed G N Ko D L Niehoff M J Kuhar B J Hoffer L Olson H E Cannon-Spoor J M Morihisa R J Wyatt 《Science (New York, N.Y.)》1983,222(4626):937-939
Transplantation of embryonic substantia nigra into the adult rat brain decreases the motor asymmetry that is produced by dopamine receptor supersensitivity after a unilateral lesion of the substantia nigra. The authors report that this effect of transplantation is specific to grafts of substantia nigra. They also report that, in conjunction with the decrease in motor asymmetry, these grafts cause postsynaptic dopaminergic binding sites to return to normal density as measured by tritiated spiroperidol autoradiography. Thus, in animals with brain lesions, grafts of substantia nigra produce a long-term alteration in the functional status of host brain cell receptors that is associated with a reduction in the behavioral deficit. 相似文献
12.
The activity of L-dopa decarboxylase was greatly reduced in the striatum, less so in the hypothalamus, and unchanged in the cortex of brains of patients with Parkinson's disease. However, it appears that even in the striatum enough activity remained to allow for the formation of dopamine from L-dopa in patients treated with large doses of L-dopa. 相似文献
13.
Kaneko S Hikida T Watanabe D Ichinose H Nagatsu T Kreitman RJ Pastan I Nakanishi S 《Science (New York, N.Y.)》2000,289(5479):633-637
The physiological role of striatal cholinergic interneurons was investigated with immunotoxin-mediated cell targeting (IMCT). Unilateral cholinergic cell ablation caused an acute abnormal turning behavior. These mice showed gradual recovery but displayed abnormal turning by both excess stimulation and inhibition of dopamine actions. In the acute phase, basal ganglia function was shifted to a hyperactive state by stimulation and suppression of striatonigral and striatopallidal neurons, respectively. D1 and D2 dopamine receptors were then down-regulated, relieving dopamine-predominant synaptic perturbation but leaving a defect in controlling dopamine responses. The acetylcholine-dopamine interaction is concertedly and adaptively regulated for basal ganglia synaptic integration. 相似文献
14.
de la Fuente-Fernández R Ruth TJ Sossi V Schulzer M Calne DB Stoessl AJ 《Science (New York, N.Y.)》2001,293(5532):1164-1166
The power of placebos has long been recognized for improving numerous medical conditions such as Parkinson's disease (PD). Little is known, however, about the mechanism underlying the placebo effect. Using the ability of endogenous dopamine to compete for [11C]raclopride binding as measured by positron emission tomography, we provide in vivo evidence for substantial release of endogenous dopamine in the striatum of PD patients in response to placebo. Our findings indicate that the placebo effect in PD is powerful and is mediated through activation of the damaged nigrostriatal dopamine system. 相似文献
15.
吲哚丁酸对高接酥梨成活率及新梢生长的影响 总被引：2，自引：0，他引：2
本试验是在梨树高接换种中通过用不同浓度的吲哚丁酸对接穗削面进行不同时间的处理，嫁接后适时调查其成活率和新梢的生长量。结果表明：在嫁接前对接穗用吲哚丁酸作任何常规浓度和时间的处理均可显著地提高嫁接成活率，并在发芽后３～４周内可使新梢的粗度增加，长度减小。在三个浓度和三个时间的处理中，其嫁按成活率和新梢发育质量均以较高浓度的短时间处理总体效果最好。 相似文献
16.
Long-term treatment with lithium prevents the development of dopamine receptor supersensitivity 总被引：9，自引：0，他引：9
Long-term treatment of rats with haloperidol produced an increased sensitivity to the locomotor and stereotypic effect of apomorphine. This behavioral dopaminergic supersensitivity was accompanied by increased binding of [3H] spiroperidol in the striatum. Rats treated concurrently with lithium and haloperidol failed to develop both behavioral sensitivity to apomorphine and increased striatal dopamine receptor binding. The ability of lighium to prevent recurrent manicdepressive episodes may be related, in part, to its ability to stabilize dopaminergic receptor sensitivity. 相似文献
17.
Neocortical transplants in the mammalian brain lack a blood-brain barrier to macromolecules 总被引：3，自引：0，他引：3
J M Rosenstein 《Science (New York, N.Y.)》1987,235(4790):772-774
In order to determine whether the blood-brain barrier was present in transplants of central nervous tissue, fetal neocortex, which already possesses blood-brain and blood-cerebrospinal fluid barriers to protein, was grafted into the undamaged fourth ventricle or directly into the neocortex of recipient rats. Horseradish peroxidase or a conjugated human immunoglobulin G-peroxidase molecule was systemically administered into the host. These proteins were detected within the cortical transplants within 2 minutes regardless of the age of the donor or postoperative time. At later times these compounds, which normally do not cross the blood-brain barrier, inundated the grafts and adjacent host brain and also entered the cerebrospinal fluid. Endogenous serum albumin detected immunocytochemically in untreated hosts had a comparable although less extensive distribution. Thus, transplants of fetal central nervous tissue have permanent barrier dysfunction, probably due to microvascular changes, and are not integrated physiologically within the host. Blood-borne compounds, either systemically administered or naturally occurring, which should never contact normal brain tissue, have direct access to these transplants and might affect neuronal function. 相似文献
18.
D E Redmond F Naftolin T J Collier C Leranth R J Robbins C D Sladek R H Roth J R Sladek 《Science (New York, N.Y.)》1988,242(4879):768-771
Studies in animals suggest that fetal neural grafts might restore lost neurological function in Parkinson's disease. In monkeys, such grafts survive for many months and reverse signs of parkinsonism, without attendant graft rejection. The successful and reliable application of a similar transplantation procedure to human patients, however, will require neural tissue obtained from human fetal cadavers, with demonstrated cellular identity, viability, and biological safety. In this report, human fetal neural tissue was successfully grafted into the brains of monkeys. Neural tissue was collected from human fetal cadavers after 9 to 12 weeks of gestation and cryopreserved in liquid nitrogen. Viability after up to 2 months of storage was demonstrated by cell culture and by transplantation into monkeys. Cryopreservation and storage of human fetal neural tissue would allow formation of a tissue bank. The stored cells could then be specifically tested to assure their cellular identity, viability, and bacteriological and virological safety before clinical use. The capacity to collect and maintain viable human fetal neural tissue would also facilitate research efforts to understand the development and function of the human brain and provide opportunities to study neurological diseases. 相似文献
19.
Aging increases susceptibility of mouse skin to DMBA carcinogenesis independent of general immune status 总被引：3，自引：0，他引：3
P Ebbesen 《Science (New York, N.Y.)》1974,183(4121):217-218
The dependence of chemical carcinogenesis on age of target tissue was studied by repeated DMBA-treatment of mouse skin grafted from old and young syngeneic donors to young recipients. Carcinomas developed on 39 percent (1.6/41) of grafts from old donors and on 12 percent (5/41) of grafts from young donors. The incidence of nonskin lymphoid tumors was highest in male recipients bearing grafts from old donors. 相似文献
20.
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine destroys dopamine neurons in explants of rat embryo mesencephalon 总被引：11，自引：0，他引：11
Explants of embryonic rat mesencephalon were grown in organotypic culture. Addition of 10 microM 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to the culture medium for 4 to 7 days resulted in loss of dopamine cell bodies and fiber outgrowths, as observed by fluorescence histochemistry. At the same time, the cultures showed decreased uptake of tritium-labeled dopamine. However, no signs of generalized toxicity were evident when the explant cultures were viewed by light and phase-contrast microscopy. These results show that MPTP exerts a relatively selective destructive action in dopamine neurons in vitro, similar to the action observed in humans and monkeys in vivo. Pargyline (10 microM), a monoamine oxidase inhibitor, protected the dopamine neurons in the explants. Organotypic cultures provide an experimental model for the study of the properties of MPTP in vitro. 相似文献