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Biomedical subjects

M J Druse

Publications and source records attributed to M J Druse.

At least 37 records · Page 2Linked to original sources
PubMed1993

Effects of ethanol on cultured fetal astroglia.

This study investigated the effects of a 4-day ethanol exposure on cultured rhombencephalic astroglia. The contents of astroglial protein and DNA, and astroglial uptake of serotonin (5-HT) were determined. Fetal rhombencephalic astroglia were examined because of this laboratory's evidence that in utero ethanol exposure markedly impairs the development of serotonergic neurons, which are located in this fetal brain area, and because of the recently demonstrated importance of local support glia in neuronal development. The results of these experiments demonstrated that protein was significantly reduced in astroglia cultured in ethanol at either 150 or 300 mg/dl. In addition, these astroglia exhibited decreased [3H]5-HT uptake per well. However, no significant ethanol-associated differences were detected when [3H]5-HT uptake was expressed per mg protein rather than per well. In contrast to the effects of a 4-day ethanol exposure, the acute ethanol exposure did not significantly alter astroglial uptake of [3H]5-HT/well. In addition, the 4-day exposure to 50 to 300 mg/dl of ethanol did not significantly alter astroglial DNA content. In summary, it appears that a 4-day exposure of cultured fetal rhombencephalic astroglia to 150 to 300 mg/dl of ethanol reduces astroglial protein content and astroglial 5-HT uptake. A reduction in total astroglial proteins, potentially including those that act as essential growth factors, could contribute to some of the ethanol-associated alterations in central nervous system development.

Animals↗
PubMed1993

Effects of chronic ethanol consumption on G proteins in brain areas associated with the nigrostriatal and mesolimbic dopamine systems.

This study examined the effects of chronic ethanol consumption on the content of G proteins in brain areas associated with the nigrostriatal and mesolimbic dopamine systems of male Fischer 344 rats, aged 3, 5, or 13 months at the time of killing. In addition, G protein mRNA was assessed in 3-month-old rats. G proteins were examined in ethanol-fed rats because a number of studies have implicated these proteins with both the acute and chronic effects of ethanol. Brain areas associated with the nigrostriatal and mesolimbic dopamine systems were examined because of the evidence that these systems are sensitive to ethanol. The brain areas examined include the substantia nigra (SN), striatum (ST), globus pallidus (GP), frontal cortex (FCX), nucleus accumbens (NA), ventral tegmental area (VTA), and ventral pallidum (VP). These experiments demonstrated that the 3-month-old rats that consumed a 6.6% (v/v) ethanol-containing liquid diet for 4 weeks had a significant (approximately 30-40%) increase in the mRNA content of Gi3 alpha in the FCX, VTA, and VP, and a significant (approximately 20%) decrease of that for G0 alpha in the SN. Nonetheless, the content of the G0 alpha protein subunit was not altered. In addition, there were no significant differences in the content of the proteins detected by antibodies to Gs alpha, G0 alpha, Gi1 alpha/Gi2 alpha, and G0 alpha/Gi3 alpha in the FCX, NA, and ST of similarly treated older rats (5 and 13 months). The content of mRNA for the other G proteins examined in the seven brain areas of 3-month-old rats was unaffected by chronic ethanol exposure.

Alcoholism↗
PubMed1992

The effects of chronic ethanol consumption on the mesolimbic and nigrostriatal dopamine systems.

Both the mesolimbic dopamine system, which is involved with the rewarding properties of several drugs of abuse, and the nigrostriatal dopamine system, which is involved with motor function, appear to be sensitive to the effects of ethanol. In order to determine which components of the mesolimbic and nigrostriatal dopamine systems are adversely affected by chronic ethanol consumption, we assessed dopamine and DOPAC (3,4-dihydroxyphenylacetic acid) concentration and D1 and D2 receptors in several dopaminergic brain areas. These studies demonstrated that consumption of a 6.6% (v/v) ethanol-containing lipid diet for 1 month affected several components of the mesolimbic dopamine system in 3-month-old Fisher 344 rats and fewer components of the nigrostriatal dopamine system. Specifically, there was a 1.6- to 2.6-fold increase in the concentration of DOPAC in the nucleus accumbens (NA), frontal cortex (FCX), ventral tegmental area (VTA), and substantia nigra (SN). While the increase in DOPAC in the FCX and VTA was paralleled by a similar increase in dopamine, there was a significant deficiency of dopamine in the SN. These results suggest that there is an increase in dopamine turnover in the FCX, VTA, NA, and SN, which is accompanied by increased dopamine synthesis in the former two regions. Studies of dopamine receptors in control and ethanol-fed rats demonstrated a 25% loss of D1 receptors in the NA. No significant differences were found in D1 receptors in the striatum or globus pallidus. In addition, there were no differences in the number of total D2 receptors or in the conversion of the high to low affinity state of D2 receptors in the nucleus accumbens and striatum.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

Effects of in utero ethanol exposure on the developing serotonergic system.

Previous work in this laboratory demonstrated that the 19- and 35-day-old offspring of ethanol-fed rats have a significant deficiency of cortical serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA), as well as a decrease in the number of total 5-HT1 receptors in the motor and somatosensory cortex. The present studies extend our previous reports by demonstrating that there is also a deficit of 5-HT and 5-HIAA in the motor cortex but not in the somatosensory cortex. In addition, we have shown that a deficit of 5-HT1A receptors in the motor and somatosensory cortices contributes to the deficit of total 5-HT1 receptors. In contrast, we did not observe any changes in the binding to 5-HT1B receptors in these cortical regions from the 19-day-old offspring of ethanol-fed rats. The present studies also examined the effects of in utero ethanol exposure on the early development of the serotonergic system. The results of these studies demonstrated a deficit of 5-HT and/or 5-HIAA in the brain stem as early as the 15th day of gestation (G15) and in the cortex as early as G19. In addition, we demonstrated a delay in both the normal developmental decline of 5-HT1A receptors in the brain stem and in the acquisition of cortical 5-HT1A receptors. No changes were found in the binding of [125I]cyanopindolol to 5-HT1B receptors in either region of fetal or neonatal rats exposed to ethanol in utero.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Effects of in utero ethanol exposure on the developing dopaminergic system in rats.

Previous studies from this and other laboratories suggest that dopamine is decreased in selected brain regions of postnatal rats exposed to ethanol in utero. The present study expands previous work by examining the effects of in utero ethanol exposure on dopamine D1 and D2 binding sites and dopamine uptake in postnatal rats. In addition, dopamine content in the brain stem and frontal cortex of fetal and neonatal rats was examined. The experimental results indicate that in utero ethanol exposure markedly affects the postnatal development of the dopaminergic system in the striatum and frontal cortex. We observed a marked, transient deficiency of striatal dopamine (greater than 40% decrease at 19 days) and dopamine uptake sites (approximately 25% decrease in Vmax at 35 days). The Bmax for striatal dopamine D1 binding sites was decreased by greater than 20% at both 19 and 35 days. Cortical D1 sites were markedly decreased at 19 days (greater than 40%). In contrast, the number of striatal D2 receptors was unaffected by in utero ethanol exposure at both ages. Analysis of tissue from neonatal rats demonstrated a marked dopamine deficiency in ethanol-exposed rats on postnatal day 5. In light of the proposed morphogenic actions of dopamine early in development, it is possible that the early dopamine deficiency contributes to the abnormal postnatal development of the dopaminergic system.

Animals↗
PubMed1989

The influence of cholesterol on synaptic fluidity and dopamine uptake.

The present study examined how the synaptic cholesterol/phospholipid ratio influences membrane fluidity and a transmembrane process of the dopaminergic system, dopamine uptake. Fluorescence polarization of DPH was used as a measure of membrane fluidity. The cholesterol content of synaptosomal and synaptic plasma membranes was altered using a lipid transfer protein. The results of the present study demonstrate that the transmembrane process of dopamine uptake may be inhibited by an elevated synaptic cholesterol/phospholipid ratio, which correlates with increased fluorescence polarization. Specifically, a 10-30% increase in the cholesterol/phospholipid ratio resulted in an approximately 20% increase in fluorescence polarization, a 3- to 6-fold increase in Km, a 4-fold increase in Vmax, and a marked decrease in the Vmax/Km (the first order rate constant for dopamine uptake at low substrate concentrations).

Animals↗
PubMed1988

Ultrastructural and biochemical responses of photoreceptor pinealocytes to light and dark in vivo and in vitro.

The teleost pineal organ contains functional photoreceptors that synapse with pinealofugal neurons. This study examined the effects of environmental lighting on protein content and levels of putative amino acid transmitters, as well as structural components associated with protein synthesis and neurotransmission. Goldfish subjected to continual illumination for 3 days tended to have increased pineal levels of free amino acids and protein compared to dark adapted glands. Similar responses to environmental lighting occurred in cultured glands suggesting a functional relationship to photosensory mechanisms. Morphometric ultrastructural analyses of pineal photoreceptors showed an increased size of nucleoli (especially the fibrillar component), Golgi bodies, and synaptic ribbons when glands were subjected to continuous light both in vivo and in vitro. The good agreement between protein levels and nucleolar morphology indicates a general effect of environmental lighting on photoreceptor protein metabolism, which may be related to photoreceptor outer segment renewal. Parallel changes in levels of certain amino acids (e.g., glutamate) and size of synaptic ribbons is consistent with an hypothesized role of amino acids in photoreceptor neurotransmission.

Amino Acids↗
PubMed1986

Maternal ethanol consumption: binding of L-glutamate to synaptic membranes from whole brain, cortices, and cerebella of offspring.

We examined the influence of chronic maternal ethanol consumption on the Na+- and Ca2+-independent binding of L-glutamate to synaptic plasma membranes from whole brain as well as from cortices and cerebella of developing offspring. The maximum specific binding (Bmax) of L-glutamate to the Na+- and Ca2+-independent binding sites in synaptic plasma membranes of brain peaked at 17 days of age in the offspring of both control and ethanol-fed rats, although at that age there were significantly fewer binding sites in the brains of the offspring of ethanol-fed rats. The regional localization of this deficit is not now known. However, it appears that one major glutamatergic region (the cortex) does not reflect the transient deficiency of L-glutamate sites in brain. In fact, the concentration of L-glutamate binding sites in cortical synaptic plasma membranes was significantly increased in the 20-day-old offspring of ethanol-fed rats. In contrast to the cortex, binding to cerebellar synaptic plasma membranes was comparable in 20-day-old offspring of control and ethanol-fed rats. Despite transient alterations in the concentrations of L-glutamate binding sites in brain and synaptic plasma membranes, the affinity of the sites for L-glutamate (Kd) was consistently normal in the 14- to 26-day-old offspring of ethanol-fed rats.

Alcohol Drinking↗
PubMed1986

Maternal ethanol consumption: lack of effect on synaptogenesis in layer I of the motor cortex in 19-day-old rat offspring.

Previous studies showed that in utero exposure to ethanol has an adverse effect on development of the central nervous system. Included among those abnormalities is the evidence that in utero exposure to ethanol alters the development of the cerebral cortex in terms of the arborization of pyramidal dendrites and the concentration of neurotransmitters and neurotransmitter receptors. However, limited information is available about the influence of in utero exposure to ethanol on synaptogenesis in the cortex. We examined the influence of chronic maternal ethanol consumption, prior to parturition, on synaptogenesis in layer I of the motor cortex of 19-day-old-rat offspring. Layer I (the molecular layer) was chosen because of the early timing of its development. The motor cortex was chosen because of the evidence of motor problems in children afflicted with the fetal alcohol syndrome. The results of these studies demonstrated that the 19-day-old offspring of rats that were pair-fed, using control or 6.6% (v/v) ethanol-containing liquid diets on a chronic basis prior to parturition, had a comparable density of synapses and distribution of paramembranous density lengths in layer I of the motor cortex as well as a comparable thickness of cortical layer I. Thus, evidence by this and other laboratories, of cortical neurotransmitter and dendritic abnormalities are not reflected in synaptic changes in layer I of the motor cortex at 19 days. It is possible that synaptogenesis is affected at another age or in other regions of the cerebral cortex.

Animals↗
PubMed1985

Synaptic membrane phospholipids: effects of maternal ethanol consumption.

The cholesterol and phospholipid content and phospholipid composition were determined in synaptic membranes from the 17- to 31-day-old offspring of rats that were pair-fed either a control or 6.6% (v/v) ethanol liquid diet on a chronic basis prior to parturition. At all ages examined, the major synaptic membrane phospholipid was phosphatidyl choline (greater than 40%). Other prominent synaptic membrane phospholipids included phosphatidyl ethanolamine (approximately 17 to 21%), ethanolamine plasmalogen (approximately 5 to 16%), and phosphatidyl serine (approximately 13%). Smaller proportions of sphingomyelin (4 to 7%), phosphatidyl inositol (approximately 1%), and phosphatidic acid (approximately 1%) were detected. Between 17 and 31 days of age, there was a significant decrease in the proportion of phosphatidyl choline and a significant increase in the proportion of ethanolamine plasmalogen. When the offspring of control and ethanol-treated rats were compared, no significant differences were found in either the yield of synaptic membrane protein, or in the concentration of synaptic membrane cholesterol and total phospholipid. However, the proportion of ethanolamine plasmalogen was significantly decreased in the 24-day-old offspring of ethanol-treated rats, suggestive of a delay in the normal development-related increase of this lipid. In addition, there was a small increase in the proportion of sphingomyelin in the 31-day-old offspring of ethanol-treated rats.

Animals↗
PubMed1985

Dopamine, serotonin, and acid metabolites in brain regions from the developing offspring of ethanol-treated rats.

Female rats were pair-fed control or ethanol liquid diets on a chronic basis prior to parturition. Six brain regions (hypothalamus, cerebellum, brain stem, cortex, corpus striatum, and hippocampus) were dissected from 19- and 35-day-old rat offspring for the determination of dopamine (DA), serotonin (5-HT), 3,4-dihydroxyphenylacetic acid (DOPAC), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA). DA, 5-HT, and the acid metabolites were separated simultaneously by reverse-phase HPLC and were quantitated using electrochemical detection. Between 19 and 35 days of age in control rats we observed an increase in the concentration of 5-HT and 5-HIAA in the corpus striatum and hippocampus and a decrease in these compounds in the cerebellum. In addition, there was a development-related decrease of 5-HIAA in the hypothalamus and an increase in the brain stem. During the same age period the concentration of dopamine increased in the hypothalamus and corpus striatum. There was also a development-related decrease in the concentration of DOPAC in the corpus striatum and an increase in the cortex as well as a decrease in HVA in the cerebellum and cortex. In comparison to age-matched control animals the 19- and 35-day-old offspring of ethanol-treated rats had a lower concentration of 5-HT and/or 5-HIAA in the cortex, cerebellum, and brainstem. In addition the 35-day-old offspring of ethanol-treated rats exhibited a decrease in DA and HVA in the cortex. The results of the present study suggest that in utero ethanol exposure affects both the serotonergic and dopaminergic systems in brain.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1985

Maternal undernutrition during lactation: effect on amino acids in brain regions of offspring.

Sprague-Dawley dams were fed either a protein-calorie deficient or control diet from day 5 to day 21 after parturition. The concentrations of seven amino acids (aspartate, glutamate, gamma-aminobutyric acid, glycine, glutamine, serine, and taurine) were determined in brain regions from 17-day-old undernourished offspring and from 35-day-old rehabilitated rats. The brain regions examined were the cortex, cerebellum, corpus striatum, hippocampus, hypothalamus, brainstem, and midbrain. At 17 days of age, taurine was the amino acid with the highest concentration, whereas at 35 days glutamate had the highest concentration. This change was due to the fact that the concentration of taurine decreased significantly in all brain regions between 17 and 35 days, whereas the concentration of glutamate remained high or increased somewhat in all brain regions except the hypothalamus and brainstem. When the age-matched offspring of control and undernourished rats were compared, several interesting and significant differences were found. The concentrations of glutamate and aspartate were significantly lower (decreased 16-34%) in the cerebellum, brainstem, cortex, and midbrain in 17-day-old undernourished rats. The aspartate level was also significantly decreased in the corpus striatum and hypothalamus in 17-day-old offspring. However, the deficiencies of aspartate and glutamate were transient and reversible. In contrast, the concentration of taurine was increased in the hypothalamus (31%) and hippocampus (12-33%) at both 17 and 35 days of age and in the midbrain (17%) at 17 days. Other transient abnormalities in amino acid levels were found in undernourished offspring. The results of these experiments suggest that undernutrition during lactation causes delayed CNS development, which is manifested in altered concentrations of the neurotransmitters aspartate, glutamate, and taurine.

Amino Acids↗
PubMed1985

Gangliosides in axolemmal and synaptic membrane fractions from developing rats: effects of maternal ethanol consumption on offspring.

Previous work from this laboratory has shown that in utero exposure to ethanol significantly alters the synthesis of glycoproteins in synaptic, axolemmal, and myelin membranes from developing rats. In an attempt to determine whether in utero exposure to ethanol similarly alters the synthesis of other glycoconjugates involved with cell-cell interactions, the present study examined the influence of chronic maternal ethanol consumption prior to parturition on the content and synthesis of gangliosides in axolemmal and synaptic plasma membranes from developing rats. The results demonstrate that, in contrast to central nervous system glycoproteins, synaptic and axolemmal glycolipids are minimally affected by in utero exposure to ethanol. At all ages examined (17 to 34 days of age), the offspring of control and ethanol-treated rats had a comparable distribution of radiolabel among synaptic and axolemmal gangliosides, a normal concentration of ganglioside sialic acid in synaptic plasma membranes, and a near-normal distribution of sialic acid among synaptic gangliosides. The present study provides evidence which indicates that the radiolabeling patterns of axolemmal and synaptic membrane gangliosides are similar. Specifically, the most heavily labeled synaptic and axolemmal gangliosides were GT1b (20-37% of the total radioactivity) and GD1a (20-32%). A smaller proportion of radioactivity was associated with GD1b (approximately 11-16%), GM1 (5-10%), and GQ1b (4-11%), as well as with GD3 and the other monosialogangliosides (less than 5%). During the age period examined the proportion of radioactive GT1b increased in both membrane fractions.

Animals↗
PubMed1984

Glycoproteins and proteins in an axolemma-enriched fraction and myelin from developing rats: effect of maternal ethanol consumption.

The present study examined proteins and glycoproteins from an axolemma-enriched fraction from the developing offspring of female rats that were pair-fed control or 6.6% (50 g/liter) ethanol liquid diets on a chronic basis prior to parturition. In addition, this study examined the synthesis of the major CNS myelin-associated glycoprotein (MAG) as an index of myelin maturation. The results of the latter study demonstrated normal MAG maturation in ethanol-treated rats. However, a significant decrease in the proportion of radioactivity associated with MAG was found in the developing offspring of ethanol-treated rats. The major axolemmal proteins from 32-day rats included those with molecular weights of 105 K, 81 K, 62 K, 55 K, 52 K, 36 K, and 33 K. Major peaks of radioactivity were associated with fucosylated axolemmal glycoproteins with apparent molecular weights of 150 K, 130 K, 85 K, 76 K, and 64 K. Several development-related changes in the protein composition of axolemma-enriched fractions were observed in control animals. Between 22 and 32 days of age control rats exhibited a significant (P less than .05) decrease in the proportion of axolemmal proteins that had apparent molecular weights of 150 K, 105 K, and 62 K. A development-related decrease in the 105 K axolemma-associated protein did not occur during the 22-32 day age period in the offspring of ethanol-treated animals. At 22 days the proportion of this 105 K protein in affected offspring was significantly (P less than .05) less than that in age-matched control rats and comparable to that in 32-day control rats. The relative distribution of radioactivity among fucosylated axolemmal glycoproteins also changed significantly between 22 and 32 days of age. These changes include a decrease in the proportion of radioactivity associated with the 110 K, 55 K, and 52 K fucosylated glycoproteins and an increase in the proportion of radioactivity associated with the 85 K and 67 K glycoproteins. Several small, but significant (P less than .05) alterations were found associated with glycoproteins in an axolemma-enriched fraction from 22- and 32-day ethanol-treated rats.

Animals↗
PubMed1984

Myelin gangliosides in developing rats: the influence of maternal ethanol consumption.

The present study examined myelin gangliosides in the developing offspring of rats that were pair-fed control or ethanol liquid diets prior to and during gestation. Between 17 and 31 days of age, we observed an increase in the proportion of GM1 in myelin (from 15% to 38% of ganglioside sialic acid) and a decrease in the proportion of GT1b (from 26% to 4%). GM4 was detected at all ages examined. Between 17 and 31 days of age, there was an increase in the proportion of N-acetylmannosamine-derived radioactivity associated with GM1 (from 16% to 22%) and GM4 (from 5% to 13%), and a decrease in that associated with GT1b (from 24% to 4%). Small, but significant (p less than 0.05), developmentally related differences were found in GD2 and GD3. Detection of GM4 in myelin of young rats in the present study appears to depend on the use of nonpartitioning methods of ganglioside extraction. Although the distribution of myelin gangliosides and radioactivity was near-normal in ethanol-treated pups, there was a consistent decrease in the proportion and radioactivity associated with the major myelin ganglioside, GM1.

Aging↗
PubMed1982

Maternal ethanol consumption and synaptic membrane glycoproteins in offspring.

The present study was undertaken to assess the influences of chronic maternal ethanol consumption, prior to and during gestation, on the development of synaptic plasma membranes (SPMs) and on the synthesis of SPM glycoproteins in offspring. Comparisons were made between animals whose mothers were pair-fed a control or 6.6% (v/v) ethanol liquid diet in which protein accounted for either 18% (original) (C & E) or 21% (revised) (*C & *E) of the calories. In addition, groups of pups that were either cross-fostered (*C & *E) with chow-fed surrogate mothers or reverse cross-fostered (offspring of chow-fed mothers with *C & *E mothers) were examined. Ethanol and matched (same dietary group) control pups had comparable brain and body weights, brain protein content, and yield of SPM proteins during the 10-24 day age period examined. However, the yield of SPM proteins from ethanol and control offspring of and/or reared by the three groups of rat mothers that received the *E and *C liquid diets was greater than that of the offspring of rats that were fed the original diets. This suggests that the original diets were not nutritionally adequate for pregnant rats. Despite the fact that the content of SPM proteins was comparable in ethanol and matched control pups, the offspring of ethanol-treated rats had an abnormal distribution of [3H]- or [14C]-fucose-derived radioactivity among SPM glycoproteins. The SPM abnormalities were most severe in the non-cross-fostered offspring of E rats. No SPM glycoprotein abnormalities were found in the reverse cross-fostered group. The results of the present study demonstrate that chronic maternal ethanol consumption prior to parturition has a severe effect on the synthesis of SPM glycoproteins in developing offspring without affecting the content of SPMs per se. It also demonstrates the importance of optimizing the composition of liquid diets used to feed pregnant rats.

Alcoholism↗
PubMed1982

Effects of maternal protein deficiency on synaptic plasma membranes in offspring.

This study examined the influence of maternal protein deficiency during lactation on the accretion and synthesis of synaptic plasma membrane (SPM) proteins in developing offspring. It also examined the activity of Mg2+-dependent, ouabain-sensitive (Na+-K+)-ATPase in SPMs. The results of this study demonstrated that early postnatal undernutrition produces a significant deficit of SPM proteins. Despite this deficit, 10- to 20-day-old undernourished rats incorporated more [3H]-leucine into SPM proteins than age-matched control rats. The specific activity of (Na+-K+)-ATPase was decreased in SPMs from undernourished rats early in development, but was increased at 20 and 34 days of age. Interestingly, 20- and 34-day-old undernourished rats also had an increased proportion of [3H]-leucine-derived radioactivity in the band on SDS gels which corresponded to (Na+-K+)-ATPase. In summary, it appears that maternal deficiency of protein during lactation affects the synaptic plasma membranes in offspring quantitatively and qualitatively.

Animal Population Groups↗