The electrophysiological properties of substantia nigra pars compacta neurones recorded from 6-hydroxydopamine lesioned guinea-pigs in vitro

Summary Intracellular recordings were made from substantia nigra pars compacta neurones in vitro from animals with partial unilateral 6-hydroxydopamine lesions of the nigrostriatal tract. Lesions were assessed and grouped according to the severity of the strital dopamine depletion. No differences were seen between neurones from control and lesioned side nigrae as regards their membrane properties, firing rates, burst activity or percentage of quiescent neurones in any of the lesioned categories. It is concluded that following partial lesioning, the remaining substantia nigra zona compacta neurones in vitro, are functioning normally.     

The effect of bacterial melanin on electrical activity of neurons of the substantia nigra under conditions of GABA generation

The changes in spike activity of single neurons of the compact part of the substantia nigra, evoked by nucleus caudatus stimulation under conditions of long-term registration of the single and multiple, isolated and combined actions of GABA, GABA-amide, glutamine, and ethanolamine-O-sulfate (EOS) were studied in albino rats. Inhibition of poststimulus activity under GABA action was recorded and the inhibitory effect of GABA-amide was revealed. Primary excitatory and subsequent inhibitory effects of glutamine in combination with EOS were shown. The subsequent administration of bacterial melanin, synthesized by a mutant culture of Bacillus thuringiensis (BT-M) evoked a clear-cut and prolonged excitatory reaction during all the combined actions of GABA, GABA-amide, glutamine, and EOS. Preliminary administration of BT-M abolished the inhibitory poststimulus effects of GABA, GABA-amide, and EOS, as well as glutamine-induced excitation.     

电刺激黑质对脑干伤害性单位放电的影响

本实验采用单细胞外记录神经元单位放电的方法，在Ｗｉｓｔａｒ大鼠上观察到网状巨细胞核。一区伤害性神经元５７个，其中伤害兴奋性神经元（ＮＥＮ）４２个，伤害抑制性神经元（ＮＩＮ）１５个。电刺激黑质对ＮＥＮ（２９）和ＮＩＮ（８的放电呈抑制作用，其反应百分率分别由刺激黑质第１分钟时的１．０±２．１％和－２０．４±６．２％，降到第５分钟时的－８３．６±１２．３％和－６５．４±１０．７％（Ｐ＜０．０１）。刺激黑质对少数ＮＥＮ（１３）和ＮＩＮ（７）的放电有兴奋作用，其值分别由第］分钟时的２０．５±７．３％和１．０±３．４％，升高到第５分钟时的７４．５±１０．７％和２１，５±８．６％（Ｐ＜０．０５）。氟哌啶醇注入ＰＡＧ腹外侧部可阻断刺激黑质的效应，这提示从黑质到网状巨细胞核α－区存在着一条痛调制通路，而且这种通路的递质是多巴胺能的。     

Neurophysiological investigation of effects of the D-1 agonist SKF 38393 on tonic activity of substantia nigra dopamine neurons

The effects of the D-1 agonist SKF 38393 on tonic activity of rat substantia nigra pars compacta dopamine neurons were studied using extracellular, single-unit recording techniques. Unlike nonselective D-1/D-2 dopamine agonists or the D-2 agonist quinpirole, SKF 38393 did not inhibit dopamine neuronal activity when applied iontophoretically or when administered intravenously in doses up to 20 mg/kg to chloral hydrate-anesthetized rats. Moreover, pretreatment with SKF 38393 did not alter the inhibitory response of these neurons to apomorphine or the D-2 agonist quinpirole. However, in locally anesthetized, gallamine-treated, artificially respired rats, dopamine cell activity was significantly altered by i.v. administration of SKF 38393; firing rate increases and decreases were observed. Administration of the inactive enantiomer of SKF 38393, S-SKF 38393, did not induce similar changes in parallel experiments. These results support the idea that unlike D-2 autoreceptor stimulation, D-1 receptor stimulation does not exert a direct local effect on dopamine neurons in the substantia nigra pars compacta and suggest that D-1 receptor stimulation at sites postsynaptic to the dopamine cells may indirectly affect the activity of some dopamine neurons through long-loop feedback mechanisms.     

A continuous striatal infusion of 6-hydroxydopamine produces a terminal axotomy and delayed behavioral effects

Rat models of Parkinson's disease typically employ a rapid nigral injection of 6-hydroxydopamine (6-OHDA) to produce a near-complete loss of nigrostriatal dopamine neurons, and thus model end stage disease. The present report describes the use of a continuous, low dose infusion of 6-OHDA into the striatum which produces a terminal axotomy of nigrostriatal dopamine neurons and protracted behavioral response. A solution of 6-OHDA in 0.4% ascorbate, delivered at 37°C from osmotic minipumps, was stable for 8 days as determined by its retained toxicity to a dopaminergic neuroblastoma cell line. The continuous infusion of 0.2 μg 6-OHDA per h did not affect the striatal uptake of [³H]GABA, [³H]choline, or [³H]glutamate but reduced [³H]dopamine uptake by 55% within 1.5 days after the start of the infusion. The striatal infusion of 6-OHDA produced a dose-dependent reduction of striatal dopamine and DOPAC levels but did not alter HVA, 5-HT, or 5-HIAA. An increase in amphetamine-induced ipsiversive rotations occurred within 1.5 days after the acute striatal injection of 20 μg or 30 μg of 6-OHDA but required 4 days to develop with the continuous 6-OHDA infusion. The topography of the lesion mapped by [³H]mazindol binding showed that, begining by 1.5 days, a diffuse depletion of terminals encompassed much of the striatum in the 30 μg acute injection group, whereas in the continuously infused rats, the lesion was apparent only by 4 days and was restricted to a smaller and more completely lesioned area. Unlike acutely lesioned animals, continuously infused rats revealed no obvious loss of dopamine neurons in the pars compacta by 5 weeks after 6-OHDA. The continuous striatal infusion of 6-OHDA can produce a topographically limited terminal axotomy of dopamine neurons and a protracted behavioral impairment.     

GM1 ganglioside partially rescues cultured dopaminergic neurons from MPP-induced damage: dependence on initial damage and time of treatment

GM1 ganglioside is believed to be important in promoting the recovery of neurons from injury. The present study assesses the ability of GM1 to repair or prevent the damage of dopamine neurons caused by the neurotoxin 1-methyl-4-phenylpyridinium (MPP⁺). Treatment of mesencephalic cell cultures with 2.5 μM MPP⁺ resulted in the loss of 30% of tyrosine hydoxylase (TH) immunoreactive neurons. In contrast, cultures administered 100 μM GM1 ganglioside for 3 days after toxin treatment contained nearly control numbers of TH⁺ neurons (97%). This reparative effect of GM1 was reflected in parallel increases in TH enzyme activity, dopamine and dopac levels. Cultures sustaining greater insult from higher doses of MPP⁺ (5.0–10.0 μM) did not benefit from ganglioside treatment, suggesting that rescue by GM1 depended on the degree of initial damage to cells. Moreover, the timing of ganglioside treatment was critical; pretreatment with GM1 alone did not prevent or attenuate the damage caused by subsequent incubation in 2.5 μM MPP⁺.     

The nigral projection to predorsal bundle cells in the superior colliculus of the rat.

Predorsal bundle cells give rise to the major efferent pathway from the superior colliculus to the premotor centers of the brainstem and spinal cord responsible for initiating orienting movements. The activity of predorsal bundle cells is profoundly influenced by an inhibitory pathway from substantia nigra pars reticulata that uses gamma aminobutyric acid (GABA) as a neurotransmitter. The present study examines the morphological basis for this influence of substantia nigra on predorsal bundle cells in the rat. In the first experiments, the laminar distributions of the nigrotectal tract terminals and the predorsal bundle cells were compared. The predorsal bundle cells were labeled by the retrograde axonal transport of horseradish peroxidase from either the decussation of the predorsal bundle or the cervical spinal cord, while the terminations of the pathway from substantia nigra pars reticulata were labeled by anterograde axonal transport from the substantia nigra. Either horseradish peroxidase, wheat germ agglutinin conjugated to horseradish peroxidase, or Phaseolus vulgaris leucoagglutinin were used as anterograde tracers. The results showed that the distributions of both the predorsal bundle cells and the nigrotectal terminals are restricted almost entirely to the intermediate grey layer and that they overlap extensively. Predorsal bundle cells varied in size. Within the areas of maximum overlap, the majority, regardless of size, was closely apposed by nigrotectal terminals. In a second series of experiments, the synaptic contacts between nigrotectal terminals and the tectospinal component of the predorsal bundle were examined in tissue in which both the terminals and the tectospinal cells were labeled for electron microscopy. In the final experiments, the distribution and fine structure of the nigrotectal terminals were compared to those of terminals that had been labeled immunocytochemically with an antibody to glutamic acid decarboxylase, the synthesizing enzyme for GABA. The results showed that nigrotectal terminals contain large numbers of mitochondria and pleomorphic vesicles, and form synaptic contacts with the somas and proximal dendrites of tectospinal cells. These synapses have modest postsynaptic densities. In both their distribution and fine structure, these terminations resemble the glutamic acid decarboxylase immunoreactive terminals that contact tectospinal cells. Taken together, these results support the view that the nigrotectal tract is an important source of GABAergic input to most, if not all, predorsal bundle cells.     

Unilateral lesion of the nigrostriatal pathway decreases the firing rate and alters the firing pattern of globus pallidus neurons in the rat

Activities of spontaneously firing neurons in the globus pallidus of intact rats and rats that survived unilateral lesions of the nigrostriatal pathway for 3 days, 1 week, or 6-11 weeks were compared. No significant differences in neuronal firing rate, firing pattern, and number of cells per pass were observed between chloral hydrate-anesthetized control and lesioned animals. However, in locally anesthetized animals, pallidal cells fired significantly faster than in chloral hydrate-anesthetized animals, and the lesion caused a decrease in the firing rates of pallidal cells 1 week and 6-9 weeks postlesion. In addition, significant differences in the firing pattern of pallidal cells, as determined by the ratio of the mean to median interspike intervals, were seen between locally anesthetized controls and animals surviving 3 days, 1 week, and 6-9 weeks postlesion. This altered firing pattern tended to return to normal with time. The number of cells per pass was not significantly altered by the lesion. Data from this study suggest that, in locally anesthetized animals, the removal of the tonic dopaminergic input to the basal ganglia causes pallidal cells to decrease their firing rates in a time-dependent fashion and causes reversable firing pattern changes. This suggests that tonically active dopamine neurons, probably acting through the striatopallidal pathway, regulate the firing rate and mechanisms controlling the temporal ordering of spontaneous discharges of globus pallidus neurons.     

胃良性和恶性病变组织中β-半乳糖凝集素3和接骨木凝集素的表达及其临床病理意义

Objective To study the expressive levels of galectin-3(gal-3) and sambucus nigra agglutinin (SNA) and their clinicopathological significance in the benign and malignant lesions of stomach. Methods EnVisonTM immunohistochemistry for assaying gal-3 expressive level and ABC cytochemistry for determining SNA expressive level were used in conventional paraffin-embedded sections from specimens of gastric cancer(n=49), peritumoral tissues(n=20), metastastic foci of lymph nodes(n=36), and different types of benign lesions(n=80). Results The positive rates of gal-3 and SNA were significantly higher in gastric cancer tissues than those in peritumoral tissues and different types of benign lesions (P<0.05, P<0.01). The positive cases of gal-3 and/or SNA in peritumoral tissues and benign lesions showed mild- to severe-atypical hyperplasia of mucous epithelial cells. No difference was found between the primary foci and metastatic foci in gal-3 and SNA expressions (P>0.05). The positive rates of gal-3 and SNA were significantly lower in histologic grade Ⅱ, infitrating depth T1,T2 and no-metastasis of regional lymph node than those in histologic grade Ⅲ, Ⅳ, infitrating depth T3,T4 and metastasis of lymph node in gastric cancer(P<0.05). The positive rates of gal-3 and SNA were higher in lymphnede metastatic site N1 and no-metastasis of distant organs than those in lymphnede metastatic site N2, N3 and metastasis of distant organs, but no significant difference was found (P>0.05). The consistence was found between the expression of gal-3 and SNA in gastric cancer tissues (χ2=6.59,P<0.05). Conclusions The expressive levels of gal-3 and SNA may be important molecular markers of lectins for reflecting the carcinogenesis, progression and biological behaviors in gastric cancer.