Changes in the neuronal reactions of the substantia nigra to nociceptive stimuli during electroacupuncture

The nature of responses of neurones in substance nigra reticular (SNR) part of cats to nociceptive electrical stimulations and change of these responses under the action of electroacupuncture (EA) in the area corresponding to the Tsui-Sang-Li point in man have been studied. The most of the neurons studied (72.1%) responded to nociceptive stimulation either with excitation of inhibition of the impulsive activity. The EA eliminated or changed the effect of nociceptive stimulation in 73.2% of the SNR nociceptive responsive neurones. Intravenous naloxone administration blocked the effect of EA depending on a dose. A conclusion has been made that the SNR neurones are involved in the modulation of nociceptive transmission and that the EA action is directed to some restoration of the nociceptive disturbed balance between the excitatory and inhibitory processes in the SNR neuronal population.     

Membrane-permeable Bcl-xL prevents MPTP-induced dopaminergic neuronal loss in the substantia nigra

The anti-apoptotic Bcl-x_L is a promising agent to prevent neurodegeneration in Parkinson's disease, which is characterized by a demise of dopaminergic neurons. We linked Bcl-x_L to a peptide that allows its delivery across biological membranes and the blood–brain barrier. We tested the fusion protein in two models of Parkinson's Disease. Cell-permeable Bcl-x_L protected neuroblastoma cells from the selective neurotoxin 1-methyl-4-phenylpyridinium. Furthermore, its systemic application in aged mice protected dopaminergic neurons following administration of MPTP as revealed by counting of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra pars compacta . Hence, we present that a cell-permeable form of an anti-apoptotic protein can be delivered to CNS neurons through its systemic application, and we provide the proof that the delivery of this protein to the CNS neurons effectively prevents neuronal cell death in models of chronic neurodegenerative diseases.     

Innervation of the substantia nigra

This review describes inputs to neurons in the substantia nigra and contrasts them with the action of agonists for the putative receptors through which they act. Special emphasis is placed on gamma-aminobutyric acid (GABA) afferents. Dopamine released from the somato-dendritic compartment of dopamine neurons and endocannabinoids released from dopamine and GABA neurons serve as retrograde signals to modulate GABA release. The release may be fostered by Ca²⁺ release from intracellular Ca²⁺ stores, which in turn may be influenced by the inputs.The studies summarized in this review were supported by the Deutsche Forschungsgemeinschaft (FOR 302/TP-B1)     

Feeding behaviour following substantia nigra and globus pallidus stimulation in chronic cats

It is known that the lesion of the nigrostriatal and pallidofugal systems causes an experimental condition comparable to the hypothalamic sindrome, with severe aphagia and adipsia. It was considered of interest to study the effects of the low frequency long-duration stimulation of the substantia nigra and the globus pallidus on feeding behaviour. Experiments were performed on eight chronic cats with electrodes implanted in SN (pars compacta) and in the GP (pars externa). In the 2 hours of observation the food intake and the number of food-taking acts were calculated. The stimulation was induced continuously in the former hour. The modification in food intake, also on the basis of somatic behavioural observations may be ascribed to motor impairment rather than to involvement of a motivational state.     

Co-cultivation of astroglial enriched cultures from striatum and neuronal containing cultures from substantia nigra

A co-cultivation system was developed with neuron-containing (neuron-specific enolase (NSE) positive) primary cultures from the substantia nigra of 15 to 17-day old embryonic rats which were grown 1 mm apart from astroglial-enriched (glial fibrillary acidic protein (GFAp) positive) primary cultures from the striatum of neonatal rats. The astroglial cells went through a morphological differentiation with extension of processes after co-cultivation with the immunohistochemically-identified neuronal cells. The astroglial-enriched striatum cultures showed a higher active uptake of 3H-L-glutamate after co-cultivation for one week, compared to control cultures from striatum. Vmax (nmol X mg protein-1 X min-1 X was 58.4 +/- 8.3 after co-cultivation and 37.2 +/- 6.3 for control cultures. The glutamine synthetase (GS) activity was slightly increased after co-cultivation. The validity and specificity of the results were ensured. The data suggest that astroglial cells in a primary culture are influenced by co-cultivation with fetal neuron containing cultures resulting in morphological differentiation, and increases in 3H-L-glutamate uptake and GS activity.     

Synapses in the rat substantia nigra

The composition and organization of the input to the rat substantia nigra were studied with the electron microscope. Four distinct types of synaptic boutons were described. The first contained small (381 A), clear synaptic vesicles. The second type contained the small, clear vesicles and several large, dense-core vesicles. The third ending contained large, dense-core vesicles and larger (581 A) clear vesicles. The fourth ending, found on the axon hillock and other terminal boutons, contained slightly elongated, clear synaptic vesicles. The presence of these four boutons was discussed in light of the known afferent input and neurochemical composition of the substantia nigra.     

Lipid peroxidation-mediated oxidative stress and dopamine neuronal apoptosis in the substantia nigra during development.

The cellular pathways underlying naturally occurring neuronal apoptosis in the rat substantia nigra (SN) during the perinatal period remain largely unknown. Determining the mediators of this process in development may shed light on causes of premature neuronal death in adult neurodegenerative disorders, including the loss of dopamine neurons in Parkinson's disease. In the present study, we investigated whether lipid peroxidation-mediated oxidative stress mediates developmental death of nigral neurons by (1) establishing the profile of lipid peroxidation and other oxidative stress markers throughout the postnatal period both in the SN and striatum, and (2) examining whether the inhibitor of lipid peroxidation, alpha-tocopherol, protects these neurons from death. In addition to monitoring, the level of lipid peroxidation throughout development, we also measured the activities of three antioxidant enzymes, namely superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx). We have shown that lipid peroxidation and SOD activity progressively increased from postnatal day (PND) 3 to PND 42 in both SN and striatum. During this period, GPx activity remained stable, while catalase activity transiently increased at PND 8 only in the SN. Furthermore, alpha-tocopherol treatment from embryonic day 18 to PND 2 did not reduce the number of apoptotic neurons at PND 3. These results do not support the hypothesis that lipid peroxidation-mediated oxidative stress is the major mediator of nigral dopamine neuronal apoptosis during the perinatal period.     

Effects of substantia nigra stimulation on high- and low-threshold response in reticular neurons

The effects of electrical stimulation of the substantia nigra (NS) pars compacta on somatosensory response in pontine neurons (from n. reticularis pontis caudalis) and reticular cells (n. reticularis gigantocellularis) were investigated in chloralosed cats. These effects were found to be inhibitory and tended mainly towards high-threshold activation of reticular neurons: responses induced by activation of high-threshold somatic efferents were those mainly inhibited in 71% of test cells. Inhibition of low-threshold response induced by tactile stimuli emerged less clearly or not at all. Potential mechanisms and the functional significance of these SN influences on reticular neurons are discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 21, No. 6, pp. 772–780, November–December.     

The neuromelanin of the human substantia nigra

The pigment of the human substantia nigra was isolated after extraction of lipids and proteins with 2% sodium cholate in 30% ethanol followed by 2% sodium dodecyl sulfate in 10% glycerol. The pigment was hydrolysed with HI or degraded by treatment with KMNO4 and the samples were examined for compounds known to derive from pheomelanin (4-amino-3-hydroxyphenylalanine, AHP and 4-amino-3-hydroxyphenylethylamine, AHPEA), or from eumelanin (pyrrole-2,3,5-tricarboxylic acid, PTCA). The HI hydrolysis yielded AHPEA in large quantities, indicating cysteinyldopamine as the main source of the pheomelanin moiety of the neuromelanin, but also trace amounts of AHP, derived from cysteinyldopa oxidation products. Dopamine and small quantities of dopa were also obtained by HI hydrolysis of the neuromelanin. The yield of PTCA was low, but the amounts observed show that part of the neuromelanin is of the eumelanin type, a fact compatible with an occasional exhaustion of the glutathione-cysteine reduction system at the site of neuromelanin formation.     

Synaptic processes evoked in red nucleus neurons by stimulation of the substantia nigra in cats

Synaptic processes in red nucleus neurons evoked by stimulation of different parts of the substantia nigra and nucleus interpositus of the cerebellum were investigated by an intracellular recording method in acute experiments on cats. Stimulation of this sort was shown to induce mono- and polysynaptic activation of rubrospinal neurons. Monosynaptic cerebellar and nigral excitatory influences were found to be very similar. These influences were shown to converge on the same rubrospinal neurons. The functional significance of inputs from the substantia nigra to the red nucleus for movement performance is discussed.L. A. Orbeli Institute of Physiology, Academy of Sciences of the Armenian SSR, Erevan. Translated from Neirofiziologiya, Vol. 13, No. 2, pp. 149–158, March–April, 1981.     

The neuronal electrical responses of the superior cervical ganglion in the rabbit to nociceptive skin stimulation]

The patterns of tonic activity in the neurons of rabbit superior cervical ganglion at rest and during noxious stimulation of the skin were studied using intracellular recording. According to reflex changes in the activity patterns, all neurons studied were classified into three groups. Cardiac rhythmicity is more pronounced in the neurons of the second type than in those of the first type. The magnitude of the cardiac rhythmicity in both types of neurons was reduced after noxious stimulation of the skin. In the third type of neurons the cardiac rhythmicity was absent. In some neurons slow excitatory and inhibitory postsynaptic potentials appeared resulting from skin stimulation.     

Responses of cat cerebellar cortical neurons to stimulation of the caudate nucleus,globus pallidus,and substantia nigra

Stimulation of the head of the caudate nucleus in cats anesthetized with chloralose and pentobarbital evoked spike responses of the Purkinje cells and other cerebellar cortical neurons in the paramedian lobes, lobulus simplex, and the tuber of the vermis. Phasic responses in the form of simple discharges (on account of activation of the neurons through mossy fibers) appeared mainly after a latent period of 5–12 and 14–20 msec; the latent period of responses consisting of complex discharges (on account of activation of Purkinje cells through climbing fibers) was 5–6, 9–22 msec, or more. Depending on the latent period, the spike responses differed in their rhythm of generation. In response to stimulation of the caudate nucleus with a frequency of 4–6/sec recruiting responses were found. An inhibitory pause was an invariable component of the tonic responses. During stimulation of the globus pallidus responses of the same types (phasic and tonic) appeared as during stimulation of the caudate nucleus, but they differed in the distribution of the neurons by latent period of spike responses. The minimal latent period was 4 msec. Recruiting also was observed during repetitive stimulation of the globus pallidus. During stimulation of the substantia nigra Pukinje cells activated by climbing fibers responded. Evoked complex discharges appeared after a stable latent period of 8.5±0.3 msec. Arguments are put forward regarding the role of the substantia nigra, the globus pallidus, nuclei of the inferior olive, and also the thalamic nuclei in the mechanism of caudato-cerebellar oligosynaptic and polysynaptic connections.N. I. Pirogov Medical Institute, Vinnitsa. Translated from Neirofiziologiya, Vol. 10, No. 4, pp. 375–384, July–August, 1978.     

Stereotyped behaviour after cholinergic, but not dopaminergic, stimulation of the substantia nigra in rats

Stereotyped behaviour of the rat was measured after intracerebral drug application in an objective and quantitative way by means of a new method developed in this laboratory. Bilateral intranigral injection of apomorphine /APO/, a specific dopaminergic agonist, did not evoke any signs of stereotyped behaviour. Also ineffective was the application of APO in the amygdaloid nucleus. Dopaminergic blockade of the substantia nigra by topical application of triperidol, a potent dopaminergic antagonist, failed to influence the stereotypy elicited by systematic APO administrationDirect cholinergic stimulation of the substantia nigra with carbachol resulted in a dose-related stereotyped behaviour not distinguishable by sight from that evoked by systematic APO administration. The effect of intranigral carbachol was antagonized by a previous intraperitoneal injection of 10 mg/kg of atropine. Stereotypy could easily be produced also by intracaudate application of APO. Topical triperidol blockade of the caudate nucleaus prevented the stereotypy caused by intraperitoneal application of APO.It is concluded that at least a part of nigral neurons cannot be directly excited by apomorphine. However, they can be excited by carbacol and seem thus, to contain muscarinic receptors. The stimulation of these receptors results in an excitation of the neurons involved and produces marked stereotyped behaviour.     

损毁或高频刺激丘脑底核对黑质神经元的保护作用

目的：探讨损毁或高频刺激丘脑底核（STN）对帕金森病（PD）大鼠黑质致密部神经元的保护作用及其可能的发生机制。方法：应用每羟基多巴胺（6-OHDA）制备偏侧PD大鼠模型,于丘脑底核（STN）区分别植入刺激电极给以高频电刺激,或注入鹅膏蕈氨酸（IA）进行损毁后,观察PD大鼠行为改变;运用尼氏（Nissl）染色、DNA原位末端标记技术（TUNEL）、免疫组化方法检测并分析黑质致密部（SNc）神经元存活及凋亡发生情况。结果：刺激组黑质致密部凋亡神经元的阳性率显著低于模型组与损毁组（P〈0．05）。与正常大鼠相比,刺激组Bel-2染色呈强阳性,Bel-2／Bax比值较高,模型组、损毁组SNc区的Bcl-2表达有所下调,Bax表达增加,Bcl-2／Bax比值降低（P〈0．05）,虽然损毁组SNc的凋亡阳性神经元少于模型组（P〈0．05）,但二者的Bel-2、Bax的表达及Bel-2／Bax比值无显著性差异（P〉0．05）。结论：损毁或高频刺激SIN对PD大鼠黑质SNc神经元存在保护作用,高频刺激的长期保护作用更为明显。     

Effects of substantia nigra stimulation on electrical and mechanical activities of the duodeno-jejunal loop, in the cat

The effect of substantia nigra stimulation on duodeno-jejunal intraluminal pressure and electrical activity was analysed in the cat. An inhibitory influence was noted to occur on both the intestinal pressure and the electrical response activity (ERA): the effect seemed to be in correlation with the stimulus parameters employed. After bilateral vagotomy, the inhibition remained substantially unchanged. The possibility of the existence of a sympathetic pathway mediating the effect is emphasized.