BACKGROUND & OBJECTIVES: Glutamate is a major neurotrammitter in corticostriatal, subthalamopallidal, and subthalamonigral pathways and interacts with other neurotrammitters. The study was done to investigate the effects of NMDA blockade on dopaminergic responses. METHODS: We made a unilateral Parkinson model in rats by injecting 6-hydroxydopamine into the substantia nigra. Rotational behavior was observed using apomorphine (mixed Dl/D2 agonist, 0. 5 mg/kg), SKF 38393 (Dl agonist, 1. 5 mg/kg), LY-171555 (D2 agonist, 0. I mg/kg), MK-801 (uncompetitive NMDA blocker, 0. 067 mg/kg), and memantine (non competitive NMDA blocker, 10 mg/kg). RESULTS: Contralateral rotation was induced by apomorphine (total turns for 2 hours, 1160+/-154), SKF 38393 (total turns for 3 hours, 1374+/-400), and LY 171555 (total turns for 3 hours 2316+/-395). NMDA antagonists per se induced mild ipsilateral rotation (MK 801; 587+/-131, memantine; 166+36). Apomorphine induced rotation was potentiated by MK 801 (1683+/-186, p<0.05) and memantine (170+/-264, p<0.05). SKF 38393 induced rotation tended to be potetiated by MK-801 (2451+/-741, p=0.08) and memantine (1794+/-450, p=0.21), though not statistically significant. However, LY 171555 induced rotation was reduced by MK-801 (1153+/-284, p<0.05) ad memantine (22.1+/-42.5, p<0.05). CONCLUSION: NMDA blockers act synergistically with Dl- and antagonistically with D2-mediated behavioural responses, suggesting that glutamate has different interactions with Dl- and D2 pathway.
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine ; Animals ; Apomorphine ; Dizocilpine Maleate ; Glutamic Acid ; Hydroxydopamines* ; Memantine ; N-Methylaspartate* ; Oxidopamine ; Rats* ; Substantia Nigra

OBJECTIVE: It was hypothesized that dopamine agonist administration and subthalamic nucleus (STN) lesion in the rat might have a synergistic effect on the neuronal activities of substantia nigra pars reticulata (SNpr) as observed in patients with Parkinson's disease. The effects of SKF38393 (a D1 receptor agonist) and Quinpirole (a D2 receptor agonist) were compared in parkinsonian rat models with 6- hydroxydopamine (6-OHDA) after STN lesion. METHODS: SKF38393 and Quinpirole were consecutively injected intrastriatally. SNpr was microrecorded to ascertain the activity of the basal ganglia output structure. The effect of SKF38393 or Quinpirole injection on the firing rate and firing patterns of SNpr was investigated in medial forebrain bundle (MFB) lesioned rats and in MFB+STN lesioned rats. RESULTS: The administration of SKF38393 decreased SNpr neuronal firing rates and the percentage of burst neurons in the MFB lesioned rats, but did not alter them in MFB+STN lesioned rats. The administration of Quinpirole significantly decreased the spontaneous firing rate in the MFB lesioned rats. However, after an additional STN lesion, it increased the percentage of burst neurons. CONCLUSION: This study demonstrated that dopamine agonists and STN lesion decreased the hyperactive firing rate and the percentage of burst neurons of SNpr neurons in 6-OHDA lesioned rats, respectively. Quinpirole with STN lesion increased a percentage of burst neurons. To clear the exact interactive mechanism of D1 and D2 agonist and the corresponding location, it should be followed a study using a nonselective dopamine agonist and D1, D2 selective antagonist.
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine ; Animals ; Basal Ganglia ; Dopamine Agonists ; Dopamine* ; Fires ; Humans ; Hydroxydopamines ; Kainic Acid ; Medial Forebrain Bundle ; Models, Animal ; Neurons* ; Oxidopamine ; Parkinson Disease ; Quinpirole ; Rats* ; Substantia Nigra* ; Subthalamic Nucleus*

To investigate the changes in the expression of basic fibroblast growth factor (bFGF) and transforming growth factor beta 2 (TGFbeta2) in glomus cell grafts of carotid body in the rat model of 6-hydroxydopamine-induced Parkinson disease, immunohistochemical staining of bFGF and TGFbeta2 in the sections of striate body was done on the 2nd, 4th and 12th week after transplantation. The results showed that on the 2nd week after transplantation, bFGF and TGFbeta2 were not detectable in the glumous cell grafts. On the 4th week after graft, bFGF and TGFbeta2 immunoreactivity was increased within the grafts and at the graft-host interface but was restricted only to astrocytes. In the striatum surrounding the graft, bFGF was expressed persistently, while TGFbeta2 showed transient expression. It was suggested that the transient expression of TGFbeta2 was likely due more to the trauma imposed by the graft procedure than to an intrinsic. The deficiency in astrocytic bFGF early after graft may be responsible for the poor survival of grafted glomus cells of carotid body.
Animals ; Carotid Body ; cytology ; transplantation ; Female ; Fibroblast Growth Factor 2 ; biosynthesis ; genetics ; Hydroxydopamines ; Parkinson Disease ; etiology ; metabolism ; surgery ; Rats ; Transforming Growth Factor beta ; biosynthesis ; genetics ; Transforming Growth Factor beta2 ; Transplantation, Homologous

No abstract available.
Models, Animal* ; Oxidopamine* ; Parkinsonian Disorders*

No abstract available.
Animals ; Neurons* ; Oxidopamine* ; Rats* ; Substantia Nigra*

OBJECTIVE: In this experimental study, authors evaluated the effect of repeated graft of the fetal midbrain cells on rat model of hemiparkinsonism. MATERIALS AND METHODS: Following injection of the 6-hydroxydopamine into striatum, we examined the behavior (turning response to amphetamine and apomorphine) at 2, 4 and 8 weeks. Their turning behavior persisted until 8 weeks after lesion making. Only those with turning behavior of more than average 6.2turns/minute by amphetamine test were selected for transplantation. Three different methods of transplantation were assigned into three groups and compared with each other to evaluate their efficiencies in improving behavioral responses. In first method, the volume of the transplanted cells were equivalent to that of one fetal midbrain. The volume of the transplanted cells were twice as much as that of one fetal midbrain in a group with second method. The last group consisted of repeated transplantation. Here, we transplanted the same amount of fetal midbrain cells as the in group 2 with two divided doses in one month interval. RESULTS: The second and third group improved from amphetamine test significantly(p<0.05), whereas first group failed to show any significant improvement from same test. The results from second and third group were not significantly different from each other. CONCLUSION: This results suggest that transplantation of two volumes of the fetal midbrain is needed to improve the turning behavior of this model of parkinsonism. This volume can be tansplanted at once or it may be transplanted in two divided volumes with time interval, with similar effect.
Amphetamine ; Animals ; Mesencephalon ; Models, Animal* ; Oxidopamine* ; Parkinsonian Disorders ; Rats* ; Transplants*

Fetal dopaminergic or nondopaminergic cortical tissues were implanted directly into the denervated striatum of partial lesioned rat parkinsonian models. After transplantation, at rats were behaviourally tested with apomorphine and sacrificed for tyrosine hydroxylase immunohistochemical stain. The results of this study are summarized as follows : 1) Of 45 rats partially lesioned with 6-hydroxydopamine, 17 rats(37.8%) met a criteria(a minimum of 4 times/min to apomorphine-induced rotation test) of the rat parkinsonian model. 2) Eight weeks after transplantation of the fetal dopaminergic tissues into the striatum of the rat parkinsonian model, transplanted dopaminergic cells were found to be alive. Also reinnervated dopaminergic fibers were found in the previously denervated striatum. And the behavioural study suggested that the transplantation of the fetal dopaminergic neurons had influenced on the apomorphine-induced rotation. 3) Eight weeks after transplantation of the fetal nondopaminergic tissues into the striatum of the rat parkinsonian model, dopaminergic cells were not found in the previously denervated striatum. However, reinnervation of the dopaminergic fibers were found in the preciously denervated striatum. However, reinnervation of the dopaminergic fibers were found in the previously denervated striatum as well as the reduction of the apomorphine-induced rotation compared to the pregraft state. The major finding of this study support a trophic hypothesis for the mechanism of recovery in response to fetal dopaminergic or nondopaminergic tissue. The author conclude that fetal nondopaminergic tissue also had some beneficial effect in reducing apomorphine-induced rotational asymmetry probably by promoting recovery or sprouting of remaining dopaminergic fibers at the previously denervated striatum of the rat parkinsonian model.
Animals ; Apomorphine ; Dopaminergic Neurons ; Oxidopamine ; Rats* ; Tissue Transplantation* ; Transplantation ; Transplants* ; Tyrosine 3-Monooxygenase

OBJECTIVE: The purpose of this study is to investigate the effect of ipsilateral subthalamic nucleus(STN) lesioning on the spontaneous behavioral changes and the alteration of neuronal activities of deep cerebral nuclei in the rat parkinsonian model with 6-hydroxydopamine(6-OHDA). METHODS: To identify the spontaneous behavioral changes, apomorphine-induced rotational test and forepaw adjusting step were performed. We subsequently investigated the alteration of neuronal activities in the substantia nigra pars reticulata(SNpr) and globus pallidus(GP), in order to compare them with the behavioral changes in rat parkinsonian models. RESULTS: The STN lesioning in the rat parkinsonian model clearly improved behavioral changes. Compared to the normal control rats, rat PD models exhibited a significant increase in mean firing rates and the percentage of bursting neurons in the STN and SNpr. In the STN-lesioned rat PD models, mean firing rates and the percentage of bursting neurons in the SNpr were reduced and those in the GP increased. CONCLUSION: STN lesioning induced behavior improvement in rat parkinsonian models seems to be consistent with the surgical outcomes of the STN stimulation therapy in advanced Parkinsonn's disease(PD). The alteration of the neuronal activities in the SNpr and GP suggests that these sites are responsible for the improvement of parkinsonian motor symptoms observed following STN lesioning in rat parkinsonian models. The significance of bursting activity in the SNpr and GP remains obscure. Further study is necessary to elucidate the pathophysiological mechanism of PD.
Animals ; Fires ; Globus Pallidus ; Kainic Acid* ; Neurons* ; Oxidopamine* ; Parkinson Disease ; Rats* ; Substantia Nigra ; Subthalamic Nucleus

PURPOSE: Thioredoxin is an endogenous antioxidant. It regulates the activities of transcriptional factors such as NF-kB(nuclear factor kappa B)and AP-1(activator protein-1) and it increases the synthesis of cytokines, preventing cellular proliferation and apoptosis. The aim of this study was to clarify the role of thioredoxin on apoptosis-inducing neuronal cell injury. We investigated the protective effects of thioredoxin against apoptosis-inducing neuronal cell injury through intracellular mechanism by 6-hydroxydopamine and serum deprivation. METHODS: PC 12 cells were cultured in RPMI 1640 media containing 10% fetal calf serum and subcultured in 96-well plates. Each well contained 30,000 cells. Cells were treated with hydrogen peroxide, diamide or 6-hydroxydopamine 30 minutes after thioredoxin treatment and then incubated for 24 hours. Cytotoxicity and cellular viability were assessed by measuring lactate dehydrogenase(LDH) release and MTT reduction. RESULTS: Thioredoxin increased cytotoxicity of PC cells treated with 6-hydroxydopamine by increasing LDH release and decreasing MTT reduction. In the serum deprivation condition, thioredoxin increased cytotoxicity of PC cells by increasing LDH release. CONCLUSION: Thioredoxin potentiates oxidative injury through intracellular mechanisms by 6-hydroxydopamine and serum deprivation instead of protecting. The cytotoxicity of thioredoxin may be mediated by decreasing the activity of NF-kB, which has been reported recently to protect against cellular apoptosis. Evidence suppors that the cytotoxic effect was not increased in the presence of serum in this study. Therefore, we found that the antioxidant effects of thioredoxin depended on mechanisms of injuries.
Antioxidants ; Apoptosis ; Cell Proliferation ; Cytokines ; Diamide ; Hydrogen Peroxide ; Lactic Acid ; Neurons* ; NF-kappa B ; Oxidopamine ; Thioredoxins*

An apomorphine-induced rotational test has been used in the evaluation of rat parkinsonian models lesioned with neurotoxin 6-hydroxydopamine (6-OHDA). Previous parkinsonian rat models have generally been characterized by unilateral destruction of both nigrosriatal pathway and mesolimbic pathway using 6-OHDA. The authors created partial lesioned rat parkinsonian models using 6-OHDA in which there is destruction of the dopaminergic nigrostriatal pathway and sparing of the mesolimbic pathway. Rats with unilateral lesions of the substantia nigra pars compacta(SNpc) were tested for rotational asymmetry using a cylindrical rotometer device with flat bottom(diameter, 30.5cm) after administration of apomorphine. After completion of the rotation test, the animals were sacrificed and their brains were immunolabeled for tyrosine hydroxylase(TH). Analysis of anatomical and behavioral data suggests that the pattern of rotation(pivotal rotation) is more reliable index for loss of TH-immunoreactive neurons in lesioned SNpc than the total number of rotational responses to apomorphine. The exact cause of the abnormal ipsiversive rotation which some rats showed is unclear. Further research should be pursued to explain this finding.
Animals ; Apomorphine ; Brain ; Models, Animal ; Neurons ; Oxidopamine* ; Parkinson Disease ; Rats* ; Substantia Nigra ; Tyrosine