Unilateral obstruction or injury to the vas deferens can result in significant injury to the contralateral testicle. Although various pathways have been proposed, the mechanism of contralateral testicular deterioration remains controversial. The present animal study was performed to evaluate the effects of unilateral vasectomy on ipsilateral and contralateral testicular histology and fertility in rats that were chemically sympathectomized neonatally. The study comprised 40 male albino rats: 20 received a placebo and the other 20 underwent chemical sympathectomy neonatally. When 60 days old, each group of 20 rats was divided into two groups that underwent either a sham operation or an operation to create unilateral left vasectomy. Eight weeks after surgery, each male rat was housed with two known fertile female rats for 25 days, and then their testes were harvested. Mean seminiferous tubular diameters (MSTD) and mean testicular biopsy scores (MTBS) were determined for each testis. Although MSTD and MTBS were not significantly different between groups, chemical sympathectomy prevented the decrease in total fertility rates of the rats with unilateral left vasectomy in our study. Prevention of this decrease by chemical sympathectomy suggests that the sympathetic nervous system may play a role in the testicular degeneration associated with vasectomy.
Animals ; Female ; Fertility/*drug effects ; Male ; Oxidopamine/toxicity ; Rats ; *Sympathectomy, Chemical ; Testis/drug effects/*pathology ; *Vasectomy

L-dopa (l-3,4-dihydroxyphenylalanine)-induced dyskinesia (LID) is a debilitating complication of dopamine replacement therapy for Parkinson's disease. The potential contribution of striatal D₂ receptor (D₂R)-positive neurons and downstream circuits in the pathophysiology of LID remains unclear. In this study, we investigated the role of striatal D₂R⁺ neurons and downstream globus pallidus externa (GPe) neurons in a rat model of LID. Intrastriatal administration of raclopride, a D₂R antagonist, significantly inhibited dyskinetic behavior, while intrastriatal administration of pramipexole, a D₂-like receptor agonist, yielded aggravation of dyskinesia in LID rats. Fiber photometry revealed the overinhibition of striatal D₂R⁺ neurons and hyperactivity of downstream GPe neurons during the dyskinetic phase of LID rats. In contrast, the striatal D₂R⁺ neurons showed intermittent synchronized overactivity in the decay phase of dyskinesia. Consistent with the above findings, optogenetic activation of striatal D₂R⁺ neurons or their projections in the GPe was adequate to suppress most of the dyskinetic behaviors of LID rats. Our data demonstrate that the aberrant activity of striatal D₂R⁺ neurons and downstream GPe neurons is a decisive mechanism mediating dyskinetic symptoms in LID rats.
Rats ; Animals ; Levodopa/toxicity* ; Dopamine ; Parkinsonian Disorders/drug therapy* ; Oxidopamine ; Dyskinesia, Drug-Induced ; Corpus Striatum/metabolism* ; Neurons/metabolism* ; Receptors, Dopamine D2/metabolism* ; Antiparkinson Agents/toxicity*

Intermittent administrations of dopaminergic agents in hemiparkinsonian rat enhances the behavioral response to subsequent administration of the drugs. This phenomenon is known as "priming" and thought as comparable to drug-induced dyskinesia in patients with Parkinson's disease. We investigated the behavioral and electrophysiological changes in 6-hydroxydopamine (6-OHDA)-lesioned hemiparkinsonian rats after repeated administrations of apomorphine. Administration of apomorphine (0.32 mg/kg, intraperitoneal, i.p.) twice daily for 6 days enhanced the rotation induced by apomorphine from 341 turns/hour at the beginning to 755 turns/hr at the end. At the same time, the response to selective D2 agonist quinpirole (0.26 mg/kg, i.p.) was also enhanced from 203 to 555 turns/hr. Extracellular single unit recording revealed no significant difference in the basal firing rates of substantia nigra pars reticulata (SNr) neurons between the ipsilateral and contralateral side of the 6-OHDA lesion regardless of the repeated administrations of apomorphine. In SNr of the lesion side, the units with burst firing pattern were found more frequently after repeated administrations of apomorphine and the suppressive effect of quinpirole on the firing rate was enhanced. These findings suggest that the increased percentage of the burst units is the important electrophysiological change in the development of enhanced response to selective D2 agonist.
Animal ; Apomorphine/*pharmacology ; Dopamine Agonists/*pharmacology ; MPTP Poisoning/physiopathology ; Male ; Oxidopamine/toxicity ; Parkinsonian Disorders/*physiopathology ; Quinpirole/pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Dopamine D2/*drug effects ; Substantia Nigra/*drug effects/physiology

BACKGROUNDHuman amniotic epithelial cells (HAECs) are able to secrete biologically active neurotrophins such as brain-derived neurotrophic factor and neurotrophin-3, both of which exhibit trophic activities on dopamine neurons. Previous study showed that when human amniotic epithelial cells were transplanted into the striatum of 6-hydroxydopamine (6-OHDA)-induced Parkinson disease rats, the cells could survive and exert functional effects. The purpose of this study was to investigate the survival and the differentiation of human amniotic epithelial cells after being transplanted into the lateral ventricle of Parkinson's disease (PD) rats, and to investigate the effects of grafts on healing PD in models.

METHODSThe Parkinson's model was made with stereotactic microinjection of 6-hydroxydopamine (6-OHDA) into the striatum of a rat. The PD models were divided into two groups: the HAECs group and the normal saline (NS) group. Some untreated rats were taken as the control. The rotational asymmetry induced by apomorphine of the HAECs group and the NS group were measured post cell transplantation. The expression of nestin and vimentin in grafts were determined by immunohistology. Ten weeks after transplantation the density of tyrosine hydroxylase positive cells in the substantia nigra of the HAECs group, NS group and the untreated group was determined. The differentiation of grafts was determined by TH immunohistology. High performance liquid chromatography (HPLC) was used to determine monoamine neurotransmitter levels in the striatum.

RESULTSThe rotational asymmetry induced by apomorphine of the HAECs group was ameliorated significantly compared to the NS group two weeks after transplantation (P < 0.01). The grafts expressed nestin and vimentin five weeks after transplantation. TH immunohistochemistry indicated that the TH positive cells in the substantia nigra of the HAECs group increased significantly compared to the NS group (P < 0.01). Tyrosine hydroxylase (TH) positive cells in the substantia nigra of the HAEC group and the NS group were decreased compared to the untreated group (P < 0.01). Dopamine and DOPAC levels in the striatum of the HAECs group increased significantly compared to the NS group (P < 0.05). Homovanillic acid (HVA) levels in the striatum of the HAECs group increased significantly compared to the NS group (P < 0.01). In addition dopamine, DOPAC, and HVA levels in the striatum and dopamine levels in the cerebrospinal fluid of the HAECs group and the NS group were decreased compared to the untreated group (P < 0.05).

CONCLUSIONSHuman amniotic epithelial cells could be used to ameliorate the rotational asymmetry induced by apomorphine of the PD models. This could have been due to the increased content of dopamine and its metabolic products, DOPAC and HVA, in the striatum in the PD models.

Amnion ; cytology ; Animals ; Apomorphine ; pharmacology ; Chromatography, High Pressure Liquid ; Epithelial Cells ; cytology ; drug effects ; transplantation ; Female ; Homovanillic Acid ; metabolism ; Humans ; Immunohistochemistry ; Oxidopamine ; toxicity ; Parkinsonian Disorders ; chemically induced ; metabolism ; therapy ; Rats ; Rats, Sprague-Dawley

AIMTo study the relationship of neurotoxicity of 6-hydroxydopamine (6-OHDA) and the function of glutamate transporter.

METHODSUsing in vivo microdialysis together with high performance liquid chromatography (HPLC) to detect the alteration of glutamate in the striatum and extracellular fluid of the PC12 cell. The rate of apoptosis and the activity of PC12 cells are read in a flow cytometer and a photometer for enzyme-labeled assays. The function of glutamate transporter is decided by detecting the ability of L-[3H]-glutamate uptake.

RESULTS6-OHDA was shown to induce apoptosis and decrease the activity of PC12 cells. Increased release of glutamate was also found in PC12 cells and the injured striatum of the PD rats. But glutamate uptake in PC12 cells and rat striatum synaptosomes are inhibited obviously.

CONCLUSIONThe neurotoxicity of 6-hydroxydopamine is associated with declined function of glutamate transporters, which may be one important pathogenesis mechanisms of Parkinson's disease.

Amino Acid Transport System X-AG ; drug effects ; Animals ; Apoptosis ; drug effects ; Corpus Striatum ; metabolism ; Glutamic Acid ; metabolism ; Male ; Oxidopamine ; toxicity ; PC12 Cells ; Parkinson Disease ; metabolism ; Rats ; Rats, Sprague-Dawley

BACKGROUNDParkinson's disease (PD) patients with long-term levodopa (L-DOPA) treatment are suffering from severe circadian dysfunction. However, it is hard to distinguish that the circadian disturbance in patients is due to the disease progression itself, or is affected by L-DOPA replacement therapy. This study was to investigate the role of L-DOPA on the circadian dysfunction in a rat model of PD.

METHODSThe rat model of PD was constructed by a bilateral striatal injection with 6-hydroxydopamine (6-OHDA), followed by administration of saline or 25 mg/kg L-DOPA for 21 consecutive days. Rotarod test, footprint test, and open-field test were carried out to evaluate the motor function. Striatum, suprachiasmatic nucleus (SCN), liver, and plasma were collected at 6:00, 12:00, 18:00, and 24:00. Quantitative real-time polymerase chain reaction was used to examine the expression of clock genes. Enzyme-linked immunosorbent assay was used to determine the secretion level of cortisol and melatonin. High-performance liquid chromatography was used to measure the neurotransmitters. Analysis of variance was used for data analysis.

RESULTSL-DOPA alleviated the motor deficits induced by 6-OHDA lesions in the footprint and open-field test ( P < 0.01, P < 0.001, respectively). After L-DOPA treatment, Bmal1 decreased in the SCN compared with 6-OHDA group at 12:00 ( P < 0.01) and 24:00 ( P < 0.001). In the striatum, the expression of Bmal1, Rorα was lower than that in the 6-OHDA group at 18:00 (P < 0.05) and L-DOPA seemed to delay the peak of Per2 to 24:00. In liver, L-DOPA did not affect the rhythmicity and expression of these clock genes (P > 0.05). In addition, the cortisol secretion was increased (P > 0.05), but melatonin was further inhibited after L-DOPA treatment at 6:00 (P < 0.01).

CONCLUSIONSIn the circadian system of advanced PD rat models, circadian dysfunction is not only contributed by the degeneration of the disease itself but also long-term L-DOPA therapy may further aggravate it.

Animals ; Blotting, Western ; Body Weight ; drug effects ; Circadian Rhythm ; drug effects ; Enzyme-Linked Immunosorbent Assay ; Fluorescent Antibody Technique ; Levodopa ; therapeutic use ; Male ; Oxidopamine ; toxicity ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction

In order to observe neuronal toxical effect of Levodopa and investigate if using Levodopa together with Ginkgo Bilobar Extract (EGb) would be an workable method to treat Parkinson disease, rat models of Parkinson disease (PD) were made by injecting 6-OHDA stereotaxically to right side of the mesencephic ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). Rotational behavioral observation, TUNEL, immunocytochemistry, Nissl's body staining were performed to measure the difference between group treated by Levodopa (50 mg/kg every day for 3 days, 5 days, 7 days, L-dopa group) and group treated by Levodopa combined with EGb (100 mg/kg every day, E-D group). The results showed that in the L-dopa group, the numbers of apoptosis of substantial nigra, rings of rotational behavior were more than those in the E-D group (P < 0.05). The numbers of Nissl's cells in L-dopa group were fewer than in E-D group (P < 0.05). The results suggested that Levodopa had neur toxic effect and EGb may decrease the toxicity of levodopa. The combined use of EGb with Levodopa may be a workable method to treat PD and may be better than using Levodopa alone.
Animals ; Apoptosis ; drug effects ; Dihydroxyphenylalanine ; metabolism ; Drug Interactions ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Ginkgo biloba ; Levodopa ; pharmacology ; therapeutic use ; toxicity ; Male ; Neurons ; drug effects ; Oxidopamine ; Parkinson Disease ; metabolism ; pathology ; prevention & control ; Random Allocation ; Rats ; Rats, Wistar ; Substantia Nigra ; pathology

AIMTo investigate the changes in neuronal activities of the pedunculopontine nucleus (PPN) and the ventrolateral thalamic nucleus (VL) after unilateral 6-hydroxydopamin (6-OHDA) lesioning of the striatum in rats.

METHODSExtracellular single-unit recordings were perin normal rats and 6-OHDA lesioned rats to observe the firing rate and firing pattern occurring in PPN and VL neurons.

RESULTSThe firing rate of PPN neurones significantly increased from (8.31 +/- 0.62) Hz in normal rats to (10.70 +/- 0.85) Hz in 6-OHDA lesioned rats. The firing pattern changed towards more irregular and bursty when compared with the normal rats, with the firing rate increasing in regular pattern. The firing rate of VL neurones in normal rats and 6-OHDA lesioned rats were (6.25 +/- 0.54) Hz and (5.67 +/- 0.46)Hz respectively, whereas to normal animals. Surthere were no significant differences in these two groups. In addition, the firing pattern did not change in VL compared prisingly, the firing rate in burst pattern decreased significantly.

CONCLUSIONThese findings demonstrate that PPN neurons are overactive in 6-OHDAlesioned rats, indicating the participation of this nucleus in the pathophysiology of parkinsonism and the activities of VL neurons might be regulated by projection from PPN to VL.

Action Potentials ; physiology ; Animals ; Corpus Striatum ; physiopathology ; Male ; Neural Pathways ; injuries ; pathology ; physiopathology ; Neurons ; physiology ; Oxidopamine ; toxicity ; Parkinson Disease ; pathology ; physiopathology ; Pedunculopontine Tegmental Nucleus ; physiopathology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Substantia Nigra ; injuries ; pathology ; physiopathology ; Ventral Thalamic Nuclei ; physiopathology

A double toxin-double lesion strategy is well-known to generate a rat model of striatonigral degeneration (SND) such as multiple system atrophy-parkinsonian type. However, with this model it is difficult to distinguish SND from Parkinson's disease (PD). In this study, we propose a new rat model of SND, which is generated by simultaneous injection of 6-hydroxydopamine into the medial forebrain bundle and quinolinic acid into the striatum. Stepping tests performed 30 min after intraperitoneal L-dopa administration at 6 weeks post-surgery revealed an L-dopa response in the PD group but not the SND group. Apomorphine-induced rotation tests revealed no rotational bias in the SND group, which persisted for 2 months, but contralateral rotations in the PD group. MicroPET scans revealed glucose hypometabolism and dopamine transporter impairment on the lesioned striatum in the SND group. Tyrosine hydroxylase immunostaining in the SND group revealed that 74.7% of nigral cells on the lesioned side were lost after lesion surgery. These results suggest that the proposed simultaneous double toxin-double lesion method successfully created a rat model of SND that had behavioral outcomes, multitracer microPET evaluation, and histological aspects consistent with SND pathology. This model will be useful for future study of SND.
Animals ; Apomorphine/pharmacology ; Behavior, Animal/drug effects ; Corpus Striatum/drug effects/pathology ; Disease Models, Animal ; Dopamine Plasma Membrane Transport Proteins/metabolism ; Glucose/metabolism ; Injections, Intraperitoneal ; Levodopa/pharmacology ; Male ; Medial Forebrain Bundle/drug effects/pathology ; Oxidopamine/*toxicity ; Parkinson Disease/metabolism/pathology ; Positron-Emission Tomography ; Quinolinic Acid/*toxicity ; Rats ; Rats, Wistar ; Striatonigral Degeneration/*chemically induced/metabolism/pathology ; Touch/drug effects

OBJECTTo investigate the therapeutic effect of microencapsulated porcine retinal pigmented epithelial cells (RPE-M) transplantation on rat model of Parkinson's disease (PD).

METHODSPrimary porcine RPE cells were harvested by enzyme digestion and expanded in culture medium. Determine the levels of dopamine (DA) and homovanillic acid (HVA) by high performance liquid chromatography electrochemical (HPLC) assay, and the levels of brain-derived neurotrophic factor (BDNF) and glial-derived neurotrophic factor (GDNF) were detected by ELISA. Alginate-polylysine-alginate (APA) microencapsulated cells were produced by using a high voltage electrostatic system. PD rat model was established by unilateral injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle (MFB). After that, the RPE-M was transplanted into the corpus striatum of PD rat, and then the rotation test scores were recorded and biochemical changes of the corpus striatum were tested.

RESULTSThe levels of DA, HVA, BDNF and GDNF secreted by RPE were stable in the RPE culture supernatant and were not changed by the microencapsulation. Eighty-three percent rats developed PD by unilateral lesion of 6-OHDA in the MFB. The RPE-M transplantation had therapeutic effect on 33% PD rats.

CONCLUSIONPorcine RPE cells grow actively in vitro and could secrete DA, HVA, BDNF, and GDNF constantly, which does not be affected by the passage culture and the APA miroencapsulation. RPE-M transplantation of may be a curative therapy for PD.

Adrenergic Agents ; toxicity ; Animals ; Brain-Derived Neurotrophic Factor ; metabolism ; Cell Transplantation ; methods ; Cells, Cultured ; Disease Models, Animal ; Dopamine ; metabolism ; Enzyme-Linked Immunosorbent Assay ; Epithelial Cells ; metabolism ; transplantation ; Glial Cell Line-Derived Neurotrophic Factor ; metabolism ; Male ; Oxidopamine ; toxicity ; Parkinson Disease ; etiology ; surgery ; Rats ; Rats, Sprague-Dawley ; Retina ; cytology ; Swine ; anatomy & histology ; Time Factors ; Transplantation, Heterologous ; methods ; Tyrosine 3-Monooxygenase ; metabolism