P. Mandel

EFFECTS OF DI‐n‐PROPYLACETATE, AN ANTICONVULSIVE COMPOUND, ON GABA METABOLISM1

The effects on GABA metabolism of an anticonvulsant drug, di‐n‐propylacetate (DPA), were studied. Given intraperitoneally DPA increases the brain GABA content and does not change its biosynthesis from glutamic acid. However, it inhibits in vitro both glutamate decarboxylase and aminobutyrate transaminase (GABA‐T) activities. The inhibition is more pronounced on the GABA‐T and this observation might explain the increase of GABA level.

Effect of sodium n-dipropylacetate on audiogenic seizures and brain γ-aminobutyric acid level

A brain γ-aminobutyric acid (GABA) level increase has been observed after n-dipropylacetate (nDPA) treatment. A relation between brain GABA level increase and protection against seizures has been pointed out; in fact, as long as the GABA rate is higher than 1.7 μmoles/g, mice are protected against audiogenic fits. Enzymatic studies have shown that nDPA inhibits competitively GABA-transaminase (GABA-T) in regard to GABA. Dreiding models show that there is a close structural relationship between GABA and nDPA, explaining the competitive inhibition.

2',3'-cyclic Nucleotide 3'-phosphohydrolase in brains of mutant mice with deficient myelination.

—The brains of Jimpy and Quaking mice were compared with those of the corresponding normal controls during the course of development. The activity of 2′,3′‐cyclic nucleotide 3′‐phosphohydrolase (CNP) was found to be markedly reduced in the affected animals. The reduction in the Jimpy mice was greater than in the Quaking mice. The activity of CNP seems to be proportional to that of myelin in the mutant mice. A similar reduction was found in spinal cords of the mutant mice, but there was no difference in CNP activity between the sciatic nerves of the mutant mice and those of the corresponding normal controls.

The utilisation of i-dimethylaminonaphthalene-5-sulphonyl chloride for quantitative determination of free amino acids and partial analysis of primary structure of proteins

Abstract A dansylation method has been developed for the rapid partial determination of primary protein structures at the nanomole level. Modifications of published methods for the purification and chromatography of dansyl-amino acids and dansylpeptides were necessary for quantitative analysis. The amino acids composition and N-terminal amino acids of proteins can be determined by this method. After finger-printing on a preparative scale, the amino acid composition and N-terminal amino acids of each dans-peptide can also be characterised.

DEVELOPMENTAL PATTERNS OF GANGLIOSIDES AND OF PHOSPHOLIPIDS IN CHICK RETINA AND BRAIN

Abstract— The changes in phospholipids and gangliosides during ontogenesis of chick retina have been compared with those in brain. Three phases of accumulation of ganglioside NeuNAc in the retina were detected. In contrast, brain NeuNAc rapidly increased during embryonic life until hatching, followed by a slower increase up to the adult stage. The phospholipid changes in retina and in brain occur in a‐similar manner to the variations observed for gangliosides, however in retina the changes of phospholipid content are less marked than in brain, during embryonic life. There were marked changes in the retina and brain ganglioside patterns with age. Gd3 and Gd1b decreased rapidly in per cent; correspondingly, Gd1a increased during embryonic life and became the major ganglioside in place of Gd3. There was a similarity between ganglioside patterns of chick retina and brain. Except for some slight variations during embryonic life, the retinal phospholipid pattern did not change noticeably.

Protective effect of adenosine and nicotinamide against audiogenic seizure

Abstract Intraperitoneal injection of adenosine into Swiss albino mice, RB strain, sensitive to audiogenic convulsions, rapidly produces, in proportion to the dose administered: sedation, modification of the EEG, lowering of arterial pressure and protection against audiogenic seizures. Simultaneous injection of adenosine and nicotinamide, produces the most striking protection, the effect being independent of all the others. During the protective period to convulsions, there is an elevation in the energy rich compounds, ATP and phosphocreatine, which is attributable to a reduction in their rate of degradation. During the same period, a diminution in the cerebral level of noradrenaline takes place. The pharmacological effects of adenosine appear to oppose those of its structural analogue, caffeine, with regard to mobility, arterial pressure, basal metabolic rate and body temperature.

HIGH AFFINITY UPTAKE OF L-GLUTAMATE AND L-ASPARTATE BY GLIAL CELLS

The presence of an efficient, high affinity uptake system specific for L‐glutamate and L‐aspartate has been demonstrated in cultured glial cells originating from syrian hamster astroblasts (line NN). The system was found to be temperature dependent, to require sodium ions and its structural specificity is similar to systems studied previously in brain slices and synaptosomes. Co‐culturing of the glial cells with neuroblastoma cells brought about only minor changes in structural specificity while values of kinetic parameters remained virtually unchanged. The temperature dependence and the susceptibility to metabolic inhibitors suggest that the uptake is mediated by an active transport system.

Poly(adenosine diphosphate ribose)

Publisher Summary This chapter discusses the higher-order structure of poly(adenosine diphosphate ribose) [poly(ADPR)], poly(ADPR) polymerase purification and its properties, and molecular mechanisms of histone- and elongation-factor (EF-2)-ADP-ribosylation. The precise biological function of the poly(ADP-ribosylation) reaction has not yet been unequivocally established. However, the results are consistent with the occurrence of rapid transient modifications of proteins in localized regions of chromatin. These alterations in chromatin conformation appear to be induced by DNA strand breakage leading to the DNA repair process or to the differentiation process. Thus, after analytical studies in vitro —such as enzyme purification and properties determination and enzyme activity measurements in isolated nuclei—the use of new sensitive analytical techniques in vivo should allow a better understanding of the biological functions of mono and poly(ADPR). The chapter also discusses the process of DNA-repair as one of the biological functions of poly(ADPR) polymerase and presents new techniques for poly(ADPR) studies including immunological analysis.

Demonstration of a specific localization of carbonic anhydrase C in the glial cells of rat CNS by an immunohistochemical method

The localization of carbonic anhydrase C isoenzyme in the central nervous system (CNS) of the rat has been investigated using the indirect immunoperoxidase technique, at both optic and electron microscopic levels. Evidence is presented for a specific localization of the enzyme in the cytoplasm of the oligodendrocytes and astrocytes. Myelinated fibers show a weak staining. The positive reaction is restricted to the cytoplasmic areas of the myelin sheath and does not appear in the compact myelin. Neuronal cell bodies do not stain at all. A strong positive reaction to the antiserum was also observed in the choroid plexus.

A study of lipid components in brain of the 'jimpy' mouse, a mutant with myelin deficiency.

(1) Brain composition and developmental changes were investigated in a mutant (‘Jimpy’) mouse characterized by a severe myelin deficiency.