Probing brain chemistry with electroanalytical techniques.
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Animals↗
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Effects of undernutrition and protein malnutrition on brain chemistry of rats.
The present study was undertaken to assess the effects of different degrees of nutritional restrictions during fetal life, suckling, and after weaning on the chemical composition of the brain. At 42 days of age, the rats were killed, and the brains were processed for analyses. The rats exposed to severe protein malnutrition after weaning had lower brain weights than those on controls. The brain seems to be resistant to the effects of moderate protein malnutrition imposed during suckling or after weaning. Thus, the brain is either resistant to the effects of mild nutritional deficiency imposed during suckling, or brain composition is very responsive to nutritional rehabilitation initiated after weaning. The effects of severe undernutrition during suckling were not, however, reversed when adequate nutrition was initiated after weaning. The suckling period seems to be critical during development, as the process of myelination was lowered and the levels of electrolytes were irreversibly disturbed. The brains of the rats born to the mothers protein malnourished during gestation were not significantly different from those of controls. The brain seems to be either preferentially protected from the effects of malnutrition imposed during fetal development, or the brain component are very responsive to nutritional rehabilitation initiated immediately after birth. It is suggested that the mother's nutritional status during gestation does not significantly affect the development of the brain. When the young were born to and nursed by protein-malnourished mothers, the growth and the maturation of the brain in such animals were similar to those in rats moderately undernourished during suckling. Growth and maturation of the brain are affected by a lowered level of protein in the diet. Moderate undernutrition imposed during suckling is not important, but the effect is maximum when undernutrition is severe during this period. The suckling period is therefore, comparatively more critical during development.
Acetylcholinesterase↗
Hypnotic effect of tryptophan analog in rats.
The effects of DL 2-amino-3-(1-naphthyl) propanoic acid, a tryptophan analog, on sleep and brain chemistry were investigated in rats. Similar to previous findings with tryptophan, the tryptophan analog (30 mg/kg, IP) reduced slow-wave sleep (SWS) latency. The reduction in SWS latency occurred at a time when 5-hydroxytryptamine (5-HT) concentration was reduced in the cortex, pons-medulla and striatum-thalamus with no change in the concentration of 5-hydroxyindoleacetic acid, a major metabolite of 5-HT. At the same time, norepinephrine concentration was reduced in the cortex, hippocampus and striatum-thalamus with a marked reduction (40%) in cortical dopamine (DA). The reduction of cortical DA coincided with a 53% decrease in homovanillic acid, a major metabolite of DA. The behavioral effect of tryptophan analog for six hours, as monitored by the EEG, was an increase in SWS by 25 min and a decrease in waking by 29 min. These data suggest that the effects of the tryptophan analog on sleep may be due to the attenuation of the activity of brain catecholamines and imply that tryptophan may as well produce its hypnotic effect via a similar mechanism.
Animals↗
Social grouping cannot account for cerebral effects of enriched environments.
Several experiments were conducted to test whether, as suggested by Welch et al. in this journal, mere group living (social stimulation) can account for the significant differences in measures of brain anatomy and brain chemistry that develop between rodents housed in groups in enriched environments and rodents housed singly in restricted environments; the alternative hypothesis was that features of the inanimate environment can significantly affect brain measures of animals living in a social group. Groups of 12 male rats were assigned for 30 days to several types of environment: (a) large cage without stimulus objects, (b) large cage containing varied stimulus objects, (c) large cage containing a maze whose pattern of barriers was changed daily, and (d) a seminatural outdoor environment; in each experiment, littermates of rats in the social conditions were housed in isolation in small colony cages. At the end of the 30-day period, measures were taken of weights of brain regions, RNA and DNA contents of regions of cerebral cortex, and acetylcholinesterase activities of brain regions. Although the number of rats housed together was constant for conditions a--d and cage size was constant for conditions a--c, the magnitudes of the cerebral measures varied significantly as a function of the inanimate stimulus conditions. The differences from isola;ion-housed littermates was greatest in condition d and smallest in condition a. Thus, social grouping alone is inadequate to explain the cerebral effects of enriched environments and the inanimate stimulus conditions must be taken into account.
Acetylcholinesterase↗
The fatty acid composition of sphingomyelin from adult human cerebral white matter and changes in childhood, senium and unspecific brain damage.
A micromethod for the investigation of the fatty acid composition of sphingomyelin in presented. In the cerebral white matter of 17 normal adult brains, analyzed for reference, the predominant fatty acids are C 18:0 and C 24:1. Our results are in agreement with those of other authors. Short chained fatty acids are relatively increased in young children; this shift is typical of "immature" myelin. Similar changes are described here in old persons and cases of non-specific brain damage associated with demyelination (autolysis, chronic uremia, juvenile chorea). Sphingomyelin fatty acid composition can be considered a sensitive measure of both disturbed myelination and demyelination.
Adolescent↗
[Comparative study of the fatty acid composition of glycerophosphatides from whole vertebrate brain and portions of it].
Fatty acids of phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and monophosphoinositide were studied in the whole brain, in the forebrain and the brain stem in the frog Rana temporaria, tortoise Emys orbicularis, hen and cat. Every family of phospholipids (PL) possesses a characteristic fatty acid pattern irrespectively of the brain part. There are regular topologic differences in the fatty acid composition of PL, namely the relative amount of saturated and polyenoic acids is higher and that of monoenoic acids lower in the forebrain as compared to the brain stem. The increase in the relative size of the forebrain, occurring in the evolution of vertebrate brain, exerts a definite influence on the fatty acid composition of the total brain. Nevertheless this increase in the size of the forebrain does not solely determine the fatty acid composition of the total brain. Similar changes are occurring in all brain parts: the relative amount of saturated fatty acids of PL is increasing and that of unsaturated acids decreasing. The evolutionary deductions derived from the biochemical study of the total brain find confirmation in the investigation of the brain parts.
Animals↗
[Concentration and composition of gangliosides in portions of the vertebrate brain].
Studies have been made on gangliosides from various parts of the brain in 5 species of cartilaginous fishes, 2 species of teleosts, 2 amphibian species, 2 avian species and 3 species of mammals. Almost in all the species investigated, the highest content of gangliosides per weight unit of the brain were found in the forebrain (determinations were carried out by sialic acid, sometimes by sphingosine). Ganglioside content of brain structure in warm-blooded animals is higher that in corresponding structures of fishes and amphibia. Comparative studies on ganglioside composition in the brain of fishes and mammals indicate that brain structures exhibit the same pattern of molecular organization, as the whole brain of the species studied (high polysialoganglioside content in teleosts, predominance of gangliosides with a short carbon chain in cartilaginous fishes, etc.). Besides this fact, peculiarities of composition typical of the brain structures were found as well (more polar composition of gangliosides of the cerebellum and some other ones).
Animals↗
Studies on neuronal lipid.
The procedure for bulk preparation of nerve-cell perikarya from pig brain-stem is briefly described. This method has definite merits with regard to the preservation of the intracellular structures as well as the preservation of the processes. The chemical composition of the isolated nerve-cell perikarya is presented. The nerve-cell perikarya are characterized by the absence of cerebroside and sulfatide. Diffuse distribution of ganglioside on the cell surface is suggested. The lipid content of the nerve-cell perikarya isolated by different methods is discussed. Lipid composition of the invertebrate nervous tissue is discussed. The submicrosomal membranes of rat brain are isolated, and their chemical and morphological properties are discussed. Ribosome-free membranes are characterized by the high content of glycolipids including gangliosides, as well as by the high activity of Na, K-ATPase, whereas ribosome-bound membranes are characterized by the absence of glycolipids, as well as by the low activity of Na, K-ATPase. The molecular organizations of lipid in submicrosomal membranes are demonstrated.
Adenosine Triphosphatases↗
[Denaturation changes in the proteins of the membrane structures of the brain during deprivation of the paradoxical stage of sleep].
24--96-hour REM-sleep deprivation entailed a rise of SH-group content in the proteins of the rat diencephalon and mesencephalon tissue homogenates, whereas SH-group content of the homogenates of the cortex, pons with medulla oblongata, and cerebellum remained unchanged. Neither did the content of SH-groups change in the soluble protein fraction nor the content of low-molecular thiol substances in the brain parts under study. From among the subcellular fractions of the brain-stem homogenate, the increase of SH-group content after 24-hour REM-sleep deprivation occurred in the synaptosomal and nuclear fractions but not in the mitochondrial one. The REM-sleep deprivation did not affect the --S--S-group content in these fractions. In the anterior parts of the brain-stem only REM-sleep deprivation led to conformational changes of structural proteins towards their denaturation but without rupture of the disulfide bonds.
Animals↗
[Specific neuronal membrane lipids].
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Brain Chemistry↗
Prophylactically administered phenytoin. Effects on the development of chronic cobalt-induced epilepsy in the cat.
In chronic cobalt-induced experimental epilepsy in the cat, there are alterations in behavior, electroencephalograms, and brain sodium, potassium adenosine triphosphatase (Na,K ATPase) activity. The electrographic and enzymatic changes occur both in focus and homotopic cortex, and are time related. The onset of EEG paroxysms consistently precedes increases in Na,K ATPase activity, indicating that the enzymatic change is adaptive. Prophylactic treatment with phenytoin (formerly diphenylhydantoin) prevents these chronic alterations from developing, although some early changes do occur. After the drug is withdrawn following 28 days of therapy, treated animals still demonstrate no evidence of epileptiform discharges or changes in Na,K ATPase activity, although these changes persist in untreated cats. Given properly, phenytoin may prevent alterations in brain, which can result in the formation of a hyperexcitable population of cells. These data support the efficacy of early pharmacologic prophylaxis in posttraumatic epilepsy.
Adenosine Triphosphatases↗
Clinical and biochemical aspects of trichopoliodystrophy.
The clinical and biochemical evaluation of 6 patients with trichopoliodystrophy indicates that the disease process can begin in utero and is related to a selective abnormality in copper metabolism. Examination of 2 infants on the first day of life revealed abnormal neurological signs, a characteristic hair abnormality, and elevated levels of copper and ceruloplasmin. Decreased hepatic copper levels and increased urinary copper excretion were documented during the first week. The 2 neonates demonstrated a progressive decrease in blood copper levels in the first month of life. Four infants identified at ages 2 to 11 months had low values for blood copper and ceruloplasmin. All infants had progressive neurological dysfunction, and 4 of the 6 died at ages ranging from 2 1/2 months to 5 1/2 years. Parenteral copper therapy achieved normal blood and hepatic copper levels in 1 patient, but the copper values in the cerebral cortex and white matter were significantly decreased compared to control specimens.
Amniotic Fluid↗
Diffuse cerebral ischemia in the cat: III. Neuropathological sequelae of severe ischemia.
The neuropathological consequences of sever diffuse cerebral ischemia were investigated in an animal model in which postischemic alterations of regional brain blood flow and energy metabolism had been previously characterized. Pentobarbital-anesthetized cats received either 15 or 30 minutes of ischemia produced by basilar artery and bilateral carotid artery occlusions plus mild hypotension; this was followed by 60 to 90 minutes of normotensive recirculation. The brains were perfusion-fixed for light microscopy. Both insult durations resulted in unequivocal ischemic cell change affecting neurons of the cerebral neocortex, striatum, thalamus, and hippocampus and portions of the rostral brainstem. Animals with 30 minutes of prior ischemia differed from those with 15 minutes of ischemia in showing a more apparent regional accentuation of ischemic change in the parasagittal cortical gyri--the sites of previously documented focal postischemic heterogeneities of blood flow and metabolism. In other respects, however, the overall distribution and spectrum of severity of the ischemic alterations were similar for the two insult durations. These data support the view that significant permanent neuronal injury may result from a period of cerebral ischemia as brief as 15 minutes.
Animals↗
History of recognition molecules in the brain, with special reference to the pharmacology of brain gangliosides.
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Animals↗
Immunofluorescence study of LRF neurons in man.
Human LRF neurons were characterized by immunofluorescence, using rabbit immunesera against unconjugated synthetic LRF, previously adsorbed on polyvinylpyrrolidone. These neurons, which vary in number from one specimen to another, are mainly concentrated in the mediobasal hypothalamus (infundibular and premammillary nuclei in particular) and in the lamina terminalis and the neighbouring preoptic area. The give rise respectively to a hypothalamo-infundibular LRF tract (ending around the capillaries of the primary portal plexus of the infundibulum) and to a preoptico-terminal tract (ending mainly around the capillaries of the primary and secondary plexuses of the vascular organ of the lamina terminalis and, in addition, between the ependymal cells lining its ventricular surface). It is suggested that these two tracts could be implicated in the tonic and cyclic control of gonadotropic secretion. Some reactive neurons are also present in the septal and pericommissural regions and in the retromammillary area and rostral mesencephalon. These neurons give rise to various extrahypophyseal LRF tracts, probably ending in the telencephalon and the brainstem. It is suggested that LRF, in addition to its major "prehypophysiotropic" action, is able to modulate the activity of certain telencephalic or mesencephalic structures.
Adult↗
Reinitiation of directed nerve fiber growth in central monoamine neurons after intraocular maturation.
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Animals↗
alpha-Albumin (glial fibrillary acidic protein) in normal and pathological human brain and cerebrospinal fluid.
alpha-Albumin, a specific brain protein observed after agar gel electrophoresis and shown to be identical to the later described GFA, has been determined in normal and pathological human central nervous system and cerebrospinal fluid. The outcome of this study underlines the value of the detection of specific proteins of the brain in biological fluids.
Albumins↗
Effects of clozapine, thioridazine, perlapine and haloperidol on the metabolism of the biogenic amines in the brain of the rat.
The effects of clozapine, thioridazine, perlapine and haloperidol on the metabolism of the biogenic amines in the brain of the rat have been investigated. Haloperidol, perlapine and thioridazine induce catalepsy and enhance the turnover of DA in the striatum as indicated by the dose-dependent increase in the DA-metabolites, HVA and DOPAC. These effects are due to blockade of dopaminergic transmission, haloperidol being far more potent than perlapine or thiridazine. Clozapine differs from these agents in that it elevates the concentration of striatal DA. The increase of the concentrations of HVA and DOPAC by clozapine is not accompanied by development of catalepsy. Therefore, clozapine seems to influence striatal DA by a mechanism other than DA-receptor blockade. All four drugs enhance the turnover of NA in the brain stem. This effect is probably secondary to the blockade of NA-receptors. There was no correlation between the effects on NA-metabolism and the EEG-arousal inhibitory activities of these agents or their clinical antipsychotic effects. Clozapine increase the concentration of 5-HT and 5-HIAA in the brain. This effect was not seen with the other drugs. Perlapine seems to enhance the turnover of 5-HT, whereas haloperidol reduced the 5-HT concentration. Thioridazine appears to have no effect on the metabolism of 5-HT.
Animals↗