Action of tetanus toxin and colchicine on synaptic membranes of the rat cerebral cortex

Purified tetanus toxin (TT), in experiments in vitro, was shown to affect neither the Na,K-ATPase activity of the synaptic membrane fraction of the rat cerebral cortex nor the inhibition of Na,K-ATPase activity produced by electrical stimulation of a suspension of synaptic membranes, nor the binding of GABA-³H by synaptosomes. TT and colchicine (1 mM) reduced the osmotic sensitivity of the nerve endings. Colchicine, in low concentrations (10^–5 to 10^–3 M), does not affect Mg- and Na,K-ATPase but, in higher concentrations (10^–2 M), it inhibits the activity of both ATPases considerably.Laboratory of General Pathology of the Nervous System, Institute of General Pathology and Pathological Physiology, Academy of Sciences of the USSR, Moscow. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 2, pp. 139–142, February, 1977.     

Changes in active uptake of noradrenalin-14C by rat brain synaptosomes during conditioning

Active uptake of noradrenalin-¹⁴C (NA-¹⁴C) by rat brain synaptosomes was shown to be inhibited by the action of ouabain (0.1 M) and during potassium depolarization. Defensive conditioning (DC) led to depression of active uptake of NA by synaptosomes. This effect may be connected both with changes in the state of the presynaptic membranes and with possible enhancement of the function of postsynaptic adrenergic receptors.Laboratory of Neurochemical Mechanisms of Conditioned Reflexes, Institute of Higher Nervous Activity and Neurophysiology, Academy of Sciences of the USSR. Laboratory of General Pathology of the Nervous System, Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. M. Chernukh.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 87, No. 2, pp. 137–139, February, 1979.     

Ultrastructural and functional changes in rat brain synaptosomes during electrical stimulation in vitro

Electrical stimulation of a suspension of rat brain synaptosomes leads to significant Ca⁺⁺-dependent liberation of endogenous noradrenalin and to a Ca⁺⁺-dependent increase in its concentration in the synaptosomes themselves. Cyclic nucleotide phosphodiesterase activity is lowered significantly under these same conditions. No disturbance of synaptosomal ultrastructure is found during stimulation. An increase in the number of electron-dense synaptosomes is observed.Laboratory of General Pathology of the Nervous System, Laboratory of Experimental Pathomorphology and Ultrastructural Characteristics of Pathological Processes, Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. M. Chernukh.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 89, No. 2, pp. 143–145, February, 1980.     

Effect of tetanus toxin on protein composition of synaptic structures of the rat brain and spinal cord

It was shown by electrophoresis on polyacrylamide gel that the content of proteins with low electrophoretic mobility rises in a Triton extract of the fractions of synaptic structures from the spinal cord tissue of rats with local tetanus, whereas no change was found in the protein spectrum in the dodecyl sulfate extract. In experiments in vitro tetanus toxin stimulated the incorporation of lysine-H³ into total proteins of cortical synaptosomes.Laboratory of General Pathology of the Nervous System, Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 79, No. 4, pp. 19–22, April, 1975.     

Changes in the state of neuronal membrane Na,K-ATPase in epileptic foci induced by penicillin in the rat cortex

Correlation between electrophysiological changes and the state of neuronal membrane Na, K-ATPase in the rat cerebral cortex was studied in epileptic foci induced by application of the sodium salt of penicillin. During the latent period and at the stage of formation of the epileptic foci, Na, K-ATPase activity was shown to be inhibited both in the primary focus and in the contralateral symetrical region. In the stage of marked paroxysmal activity Na, K-ATPase activity was inhibited only in the primary focus. In concentrations of 2·10^–6–2·10^–3 M, penicillin was shown not to affect Na, K-ATPase of unpurified rat cerebral cortical synaptosomes. It is suggested that inactivation of Na, K-ATPase may be a pathogenetic factor in the development of epileptic activity.Laboratory of General Pathology of the Nervous System, Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 87, No. 5, pp. 406–409, May, 1979.     

Use of the fluorescent probe 1-anilinonaphthalene-8-sulfonate to study the synaptosomal transmembrane potential

The transmembrane potential (TMP) of synaptosomes isolated from the rat cerebral cortex was studied with the aid of 1-anilinonaphthalene-8-sulfonate (ANS). Addition of valinomycin to the synaptosomes was accompanied by an increase in the intensity of fluorescence of the probe at 464 nm (_exc = 365 nm), which is interpreted as reflecting hyperpolarization of the synaptosomal membranes. A decrease in the K⁺ gradient on the synaptosomal membrane (a decrease in TMP), achieved by preincubation of the synaptosomes with ouabain (1 mM) or an increase in the concentration of extrasynaptosomal K⁺ from 5 to 20 mM appreciably reduced the effect of valinomycin. Valinomycin had no effect on synaptosomes exposed to osmotic shock. It is suggested that valinomycin-induced changes in the intensity of fluorescence of ANS be used as a test of preservation of the K⁺ gradient (the presence of a TMP) by synaptosomal preparations, i.e., of the active state of the synaptosomes.Laboratory of General Pathology of the Nervous System, Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR S. E. Severin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 89, No. 3, pp. 300–302, March, 1980.     

Neuropathological effects of injection of tetanus toxin into certain structures of the rat brain

The neuropathological effects of local injection of tetanus toxin (TT) into various structures of the brain were studied in experiments on rats. Definite neuropathological changes were observed in the animals, different from those found after injection of TT elsewhere. As a rule the action of TT in a given region of the brain was local. The experiments confirm the theory of generator mechanisms of neuropathological syndromes, according to which specific manifestations of the corresponding syndrome are determined by the location of a generator of pathologically enhanced excitation in a certain brain structure.Laboratory of General Pathology of the Nervous System, Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. M. Chernukh.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 87, No. 2, pp. 124–126, February, 1979.     

Enzymic micromethod of determining membrane Na,K-ATPase activity in the rat cerebral cortex

A method of determining activity of Na, K-ATPase in the fraction of unpurified synaptosomes isolated from weighed microsamples (2–3 mg wet weight of tissue) of rat cerebral cortex is described. The method is based on fluorometric measurement of ADP formed in the course of the ATPase reaction; it is highly sensitive and can be used to determine the Na, K-ATPase activity of membrane preparations with a protein content of 0.5–1.0 g per sample.Laboratory of General Pathology of the Nervous System, Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. Research Institute for Biological Testing of Clinical Compounds, Kupavna, Moscow Region. (Presented by Academician of the Academy of Medical Sciences of the USSR A. M. Chernukh.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 86, No. 10, pp. 507–509, October, 1978.     

Activation of tyrosine hydroxylase during electrical stimulation of isolated nerve endings of the rat hypothalamus

The effect of electrical stimulation on synaptosomal membrane-bound tyrosine hydroxylase (TH) activity in the rat hypothalamus was investigated. Electrical stimulation intensified respiration and glycolysis, evidence of excitation of the synaptosomes. Against this background, activity of membrane-bound TH was increased. The value of K_m for tyrosine fell from 0.091 to 0.026 mM. Inhibition of the enzyme activity by the end product of cathecholamine biosynthesis (noradrenalin) was reduced. It is postulated that the effect of depolarization on the rate of catecholamine synthesis in nerve endings is effected through modification of TH.Laboratory of Neurochemical Pharmacology, Institute of Pharmacology, Academy of Medical Sciences of the USSR. Laboratory of General Pathology of the Nervous System, Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 5, pp. 543–545, May, 1977.     

Lipid peroxidation in a focus of hyperactivity in the rat cerebral cortex

It is shown that lipid peroxidation (LPO) can participate in the mechanism of development of paroxysmal activity in the rat cerebral cortex. The appearance of epileptic activity as a result of application of the sodium salt of penicillin to the surface of the sensomotor cortex led to a sharp rise in LPO products in the fraction of unpurified synaptosomes isolated from a focus of hyperactivity. Preliminary injection of the antioxidant -tocopherol into rats abolished the LPO activation effect and considerably reduced the number of paroxysms recorded on the electrocorticogram during existence of the focus.Laboratory of General Pathology of the Nervous System, Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 89, No. 1, pp. 14–16, January, 1980.     

Spontaneous synchronization by 4-aminopyridine of acetylcholine release in the neuromuscular junction

The effect of 4-aminopyridine (4AP) on the character of acetylcholine release was investigated by intracellular recording of spontaneous synaptic activity in an isolated rate phrenic nervediaphragm preparation. No significant changes were found in the mean frequency and amplitude of miniature end-plate potentials (MEPP) in response to 4AP in concentrations of 1·10^–6 to 1·10^–3M. Meanwhile, 4AP caused the appearance of large spontaneous EPP capable of inducing spreading action potentials. 4AP changed the character of distribution of MEPP amplitudes, converting it to polymodal; in some cases the principal mode was shifted into the region of lower values. It is concluded that 4AP changes the character of acetylcholine release and potentiates spontaneous synchronization.Laboratory of General Pathology of the Nervous System, Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. Department of Pharmacology, Faculty of Internal Medicine and Hygiene, I. M. Sechenov First Moscow Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR A. M. Chernukh.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 9, pp. 259–262, September, 1979.     

Isolation and properties of an actomyosin-like protein from glial cells of bovine brain

An enriched fraction of glial cells was isolated by centrifugation in a Ficollsucrose density gradient from bovine cerebral cortical tissue, and an actomyosinlike protein (AMLP) was obtained from it. The yield of the AMLP was 0.05% relative to glial cell protein. The AMLP was found to contain bound nucleotides and to give reversible association-dissociation reactions characteristic of AMLP under the influence of Mg²⁺ ions and ATP. ATPase of glial AMLP, which is activated by Ca²⁺ ions by a greater degree than Mg²⁺, differs from the AMLP of neuronal origin.Laboratory of General Pathology of the Nervous System, Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. Department of Biochemistry, Tbilisi University. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 3, pp. 280–282, March, 1977.     

Calcium transport and ATPase activity in mitochondria and fragments of sarcoplasmic reticulum of the heart and muscles of rabbits with hypercholesteremia

Keeping rabbits on a high-cholesterol diet (1 g/kg) for 3–7 months led to an increase in cholesterol concentration in the mitochondrial membranes and fragments of the sarcoplasmic reticulum (SPR) of the myocardium and skeletal muscles. Saturation of the membranes with cholesterol led to a decrease in efficiency of the Ca-pump of the SPR, as reflected in lowering of the Ca/ATP ratio and an increase in the outflow of Ca⁺⁺ from the SPR. Under these conditions the rate of accumulation of Ca⁺⁺ was higher in SPR than in the mitochondria. Activity of mitochondrial Mg⁺⁺-activated 2,4-DNP-ATPase was reduced in hypercholesteremia.Laboratory of Molecular Pathology and Biochemistry, Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. M. Chernukh.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 89, No. 3, pp. 292–294, March, 1980.     

A new method of evaluating anxiety states and phobias in rats

Laboratory of General Pathology of the Nervous System, Research Institute of General Pathology and Pathological Physiology, Russian Academy of Medical Sciences, Moscow. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 114, No. 7, pp. 11–14, July, 1992.     

Effect of diazepam on the state of Na,K-Atpase in a cortical focus of hyperactivity induced by penicillin

Intramuscular injection of diazepam into rats in doses of 0.01 and 2 mg/kg 25–30 min after application of penicillin to the cerebral cortex was shown to lead to a disturbance of the periodic occurrence of epileptic fits (EF), to a change in their character, and to the appearance of periods of increased frequency of epileptiform discharges (ED). Injection of diazepam in a dose of 2 mg/kg 20 min before application of penicillin led to shortening of the latent period of ED in the epileptic focus and to an increase in their frequency in the period before the fit compared with the control without diazepam. EF appeared irregularly, their number was sharply reduced, and their duration increased. Injection of diazepam led to disappearance of the animal's motor response during ED and EF. Diazepam (2 mg/kg) in experiments in vivo did not affect Na,K-ATPase activity of unpurified cerebral cortical synaptosomes, but after creation of an epileptic focus it led to an increase in Na,K-ATPase activity in the primary focus and secondary foci dependent on it. It is suggested that the anticonvulsant action of diazepam may be based on its activating effect on Na,K-ATPase in neuron membranes in the epileptic focus.Laboratory of General Pathology of the Nervous System, Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 12, pp. 655–659, December, 1979.     

Emotional behavioral disorders in rats following injection of subconvulsant doses of metrazol

Laboratory of General Pathology of the Nervous System, Research Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 111, No. 2, pp. 123–126, February, 1991.     

Effect of verapamil on development of the pain syndrome in rats after sciatic nerve division

Laboratory of Pathophysiology of Pain and Laboratory of General Pathology of the Microcirculation, Research Institute of General Pathology and Pathological Physiology, Russian Academy of Medical Sciences, Moscow. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 114, No. 9, pp. 229–231, September, 1992.     

Trigeminal neuralgia of neuropathic origin

Laboratory of Pathophysiology of Pain and Laboratory of General Pathology of the Microcirculation, Research Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 112, No. 8, pp. 120–122, August, 1991.     

Effect of intranasal substance P on the Parkinsonian syndrome

Laboratory of General Pathology of the Nervous System, Research Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. Odessa Medical Institute. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 113, No. 1, pp. 16–19, January, 1992.     

Changes in cerebral cortical electrical activity in rats with compression of the infraorbital nerve

Laboratory of Pathophysiology of Pain and Laboratory of General Pathology of the Nervous System, Research Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences, Moscow. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 113, No. 5, pp. 458–459, May, 1992.