摘要:

Abstract—Neurotoxic hexacarbon compounds 2,5‐hexanedione (2,5‐HD) and methyl n‐butyl ketone (MnBK) inhibit crystalline and endogenous CNS and PNS glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH). Preincubation of the enzyme with the toxin was necessary for inhibition. The enzyme activity of GAPDH was preserved by the addition of dithiothreitol in the presence of either neurotoxin. By contrast, lactate dehydrogenase (LDH) activity was not inhibited by these neurotoxic chemicals. Neurologically inactive compounds 1,6‐hexanediol and acetone failed to inhibit GAPDH. The present data indicate that 2,5‐HD and M “BK block energy metabolism by inhibiting glycolysis at the site of GAPDH. These observations may account for the known failure of GAPDH‐dependent axonal transport and the axonal degeneration which occurs in he

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1979.tb04550.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

Abstract—Experimental hind‐limb rigidity of spinal origin was produced in cats by temporary occlusion of thoracic aorta and internal mammary arteries. In the lumbar segments (L6‐ S1) of these rigid cats, the monosynaptic reflex recorded from ventral roots was enhanced whereas the polysynaptic reflexes as well as the dorsal root reflexes were almost abolished. On morphological examination of the lumbar spinal cord, the number of interneurons was greatly reduced, whereas the small sized cells, presumably glial cells, were increased by about two times. Ventral horn motoneurons were also reduced. The lumbar spinal cords of the rigid cats were analysed for amino acid and substance P contents. Four major amino acids, aspartate, glutamate, glycine and GABA, were definitely reduced in both grey and white matter except that the glutamate level in the dorsal white was within the normal range. Content and distribution pattern of substance P were not altered in the lumbar cord of the rigid cats. These results are consistent with the notions that GABA occurs in the dorsal horn interneurons subserving primary afferent depolarisation, and that substance P is concentrated in primary afferent fibre terminals. The implications of the decrease of aspartate, glutamate and glycine in the spinal cord of rigid cats are disc

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1979.tb04551.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

Abstract—An NADP+‐linked enzyme, capable of interconverting γ‐hydroxybutyrate and succinic semialdehyde, has been isolated from hamster liver and brain. The enzyme which was isolated from liver has been purified 300‐fold and exhibits a single band by polyacrylamide gel electrophoresis. The molecular weight of the enzyme is ‐ 31,000 as estimated from gel filtration and 38,000 as estimated from sodium dodccyl sulfate gel electrophoresis. The enzyme is inhibited by amobarbital, diphenylhy‐dantoin, 2‐propylvalerate, and diethyldithiocarbamate, but not by pyrazole. The enzymes from brain and liver appear to be very similar with regard to their molecular weights and their kinetic constants for γ‐hydroxybutyrate and succ

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1979.tb04552.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

Abstract—The binding of [3H]muscimol, a potent GABA agonist, to crude synaptic membranes prepared from rat brain was studied using a filtration method to isolate membrane‐bound ligand. Specific binding was found to be saturable and occurred to two binding sites ofKd5 5 and 30 nm. Binding was Na+‐independent and enhanced by both freezing and Triton treatment. Regional and subcellular distribution studies and pharmacological characterization of specific [3H]muscimol binding are consistent with binding to the synaptic GABA rec

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1979.tb04553.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

Abstract—We surveyed the transport systems present in the brain for amino acids. Cellular transport was measured in brain slices, and capillary transport was estimated by measuringin vivothe short‐term (15 s) extraction by brain from the blood. Specific analog inhibition of uptake was used to distinguish the classes. Amino acid levels (close to physiological) were such that primarily the ‘low‐affinity’ transport was measured.In brain tissue we could distinguish 10 overlapping amino acid transport classes. Five of these, described in a number of tissues, were characterized by their substrates: alanine (A system), leucine (L system), alanine‐serine‐cysteine (ASC system), glutamic acid (Glu system), and arginine (Ly+system), respectively. The others distinguished were each fairly specific for one of the following five amino acids: glycine, proline, γ‐aminobutyric acid (GABA), taurine, and lysine. Of these 10 systems only 4 could be clearly found in capillary transport: L, ASC, Ly+, and Glu.The properties and the distribution of the transport systems are different. Examples are that at least one of the systems is present primarily only in neurons (GABA), and one primarily in glia (taurine). The specificity of some of the systems, e.g. A, is altered during development. In contrast to the properties of most other systems, there is little Na+, energy, or temperature dependence of the L system. This is reflected in the properties of capillary neutral amino acid transport when the L system is the

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1979.tb04554.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

Abstract—Axonal transport of lipids was demonstrated in the rabbit optic system using [2‐3H]glycerol and [3‐14C]serine. Following intraocular injection of these precursors, radioactive lipids were detected in the optic tract, superior colliculus and lateral geniculate body over a 31 day period. The bulk of lipid appeared to migrate at a rate equivalent to that of rapidly transported protein which, when combined with a prolonged period of release into the axon, led to a peak of transported radioactivity at 6‐10 days for the 3 tissues. The suggestion of a second peak at 17 days indicated the possibility of a smaller slow component, although another interpretation is suggested. Analysis of individual transported lipids revealed [2‐3H]glycerol to label phosphoglycerides preferentially and [3‐14C]serine to be an effective precursor for sphingolipids and certain of the phosphoglycerides. [3‐14C]Serine labeled axonally transported proteins to an even greater extent than lipids, revealing the same fast and slow components previously shown with othe

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1979.tb04555.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

Abstract—The possibility that axonally transported lipids and/or proteins might undergo transaxonal migration and become incorporated into surrounding myelin lamellae was studied by isolating myelin from optic tracts of myelinating rabbits at various times following intraocular injection of [3‐14C]‐serine and [2‐3H]glycerol. Myelin isolated by a procedure employing ethylene glycol‐bis(β‐aminoethyl ether)‐.N,N'‐tetraacetic acid had relatively constant specific radioactivity with respect to both isotopes over a 21 day period. Myelin lipids showed a gradual increase in14C specific radioactivity, attributed to reutilization of [14C]serine from the axon by a compartment of the oligodendrocyte. Free serine is postulated to arise in the axon from catabolism of axonally transported proteins (and possibly lipids) and to migrate transaxonally into the neighboring oligodendroglia. This reutilization mechanism resulted in synthesis of myelin cerebrosides, sphingomyelin, ethanolamine phosphoglycerides and possibly sulfatides, but not gangliosides or serine phosphoglycerides. The data for choline‐ and inositol‐phosphoglycerides are inconclusive. [3H]Glycerol‐labeled myelin lipids decreased slowly in3H specific radioactivity with time, indicating either that [2‐3H]glycerol does not participate in the reutilization pathway or that the label is lost in the process. Evidence is presented that3H‐ and14C‐labeled lipids are true myelin constituents. Lipids from the myelin, axolemma‐ and axon‐enriched fractions tended to converge in specific radioactivity over the 21 days, especially the former two fractions. These results together with isotope ratio changes point to an equilibration process whereby lipids are able to transfer. (or exchange) between the 3 compartments. Protein radioactivity in isolated myelin was suggested to arise from residual axon/axolemma contamination, and no evidence was found for transaxonal migration of protein into myelin. The 2 mechanisms elucidated here are believed to account for a quantitatively small portion of myelin lipid and are considered to represent

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1979.tb04556.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

Abstract—The effects of maximal electroshock (MES) and phenytoin on metabolites and cyclic nucleotides in layers of frozen‐dried cerebellum have been investigated. The four layers (molecular, Purkinje‐cell rich, granular and white matter) had remarkably homogeneous distributions of P‐creatine, ATP, glucose, glycogen, lactate, GABA and the cyclic nucleotides. MES caused dramatic decreases in P‐creatine, ATP, and glucose at 10 s after treatment, followed by a decrease in glycogen at 30 s. Lactate levels were elevated, and GABA was unchanged. Cyclic AMP concentrations were increased at 10s and cyclic GMP at 30 s. Phenytoin modified most of the MES induced changes in all the layers, although white matter was less affected by MES and/or phenytoin. Lactate concentrations were increased by MES and these effects were not altered when phenytoin was administered. The most dramatic effects of phenytoin were on the changes in cyclic nucleotides. Cyclic AMP concentrations were elevated after MES but the values returned to normal more rapidly when phenytoin was present. The drug almost obliterated the MES induced changes in cyclic GMP. The possible relationship of cyclic nucleotide concentrations and the modulation of seizure activity is

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1979.tb04557.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

Abstract—Levels of glucose, lactate, GABA and cyclic nucleotides were examined in discrete layers of the cerebellum and cerebral cortex of mice following treatment with the anticonvulsant, sodium valproate, and/or the convulsant, isoniazid. The concentrations of the metabolites were essentially uniform among the layers of each region, whether from control or from drug‐treated mice. Metabolite concentrations in the isoniazid‐treated mice were determined either 30 min after administration (preconvulsive state), or immediatley after the onset of seizures. Glucose and lactate, two markers of energy status in the brain, were only minimally affected by drug treatment. However, the levels of GABA and cyclic nucleotides were markedly different from control values in the drug‐treated animals. In the preconvulsive state, GABA levels in cerebellar layers were depressed and the cyclic nucleotides were elevated in most layers of both regions. At the onset of seizures, the reduction of GABA and the elevation of cyclic AMP in both regions was more pronounced than during the preconvulsive state. While the concentration of cyclic GMP remained elevated in the cerebellar layers at the onset of seizures, the level in the cerebral cortex returned to control values. Valproate elevated GABA in all the layers of both regions and decreased the cyclic GMP in the cerebellar layers. Generally, when valproate was administered in combination with isoniazid, it dampened the isoniazid induced changes in the metabolites. The events leading up to a seizure as well as those that sustain it may be reflected by the disparate responses of the metabolites in the cerebellum and cerebral

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1979.tb04558.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

Abstract—Acetylcholine and choline were identified and their concentrations measured, by means of gas chromatography/mass spectrometry, in extracts obtained from nerve fibers of the hindmost stellar nerve of the squidSepioteuthis sepioidea.These compounds were quantitated in samples of stellar nerve devoid of giant fiber, intact giant nerve fiber, extruded axoplasm, and axoplasm‐free giant nerve fiber sheaths. In 11 samples of stellar nerve devoid of giant fiber, weighing an average of 20.8 ± 2.3 mg (s.e.m.), 756 ± 91 pmol ACh and 8.65 ± 0.62 nmol of choline were found. The total ACh content of the largest fibre in this group (10μm in diameter), for a 5 cm length of nerve, is in the order of 0.16 pmol. The average wet weights of a single giant nerve fiber (270‐420μm in diameter) and its separate components (s.e.m.; in mg; number of fibers in parentheses) were: intact fiber, 4.58 ± 0.19 (25); extruded axoplasm, 3.38 ± 0.13 (20); sheaths, 1.21 ± 0.11 (16). The average ACh content per unit weight of sample was about 2‐3 times higher in the sheaths (5‐13 pmol‐mg−1) than in the axoplasm (2‐4 pmol mg−1), whereas the ACh concentrations estimated per unit volume of cellular water were about 40 times higher in the Schwann cell (107‐222μm) than in the axon (2‐5μm). These experimental findings establish the presence of ACh in the giant nerve fiber ofS. sepioidea.They also indicate the Schwann cells themselves as the main source for the release of ACh, responsible for their long‐lasting hyperpolarizations following the conduction of

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1979.tb04559.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY