Biomedical subjects

B Shanley

Publications and source records attributed to B Shanley.

9 recordsLinked to original sources

PubMed1995

Increased NMDA-induced excitability during ethanol withdrawal: a behavioural and histological study.

Intrahippocampal injections of N-methyl-D-aspartic acid (NMDA) leads to neurodegeneration in a dose-dependent manner. Chronic administration of ethanol to animals leads to CNS tolerance and dependence. Hyperexcitability following ethanol withdrawal is thought to be related to increased sensitivity of the NMDA receptors. The purpose of this study was to investigate this predisposition to hyperexcitability by intrahippocampal injection of low dose of NMDA. Using control and ethanol-withdrawn male Wistar rats, behavioural indices were determined immediately after injection and morphological damage was assessed after a period of recovery. There was significantly increased hyperactivity in the ethanol-treated rats immediately after injection. Morphological damage resulting from 5 nmol of NMDA was significantly greater in the CA3 region of the hippocampus in these animals. These data support the hypothesis that ethanol dependence and subsequent withdrawal is associated with increased sensitivity to NMDA which may underlie ethanol withdrawal-associated brain damage.

Animals↗

PubMed1994

Gene expression during ethanol withdrawal.

The expression of the proteins (C-FOS and C-JUN) encoded by the immediate early genes c-fos and c-jun was investigated in the brains of rats undergoing ethanol withdrawal. Both proteins were induced in the cerebral cortex, the piriform cortex, the olfactory bulb, the inferior colliculus, the granular cell layer of the cerebellum and in the brain stem, but only C-JUN was induced in the hippocampus of animals undergoing withdrawal without overt seizures. C-FOS was detected in the hippocampus only in animals with overt seizures. Maximal C-FOS expression occurred 15 hr after withdrawal while C-JUN was maximal at 24 hr. Gel-shift assays indicated the formation of AP-1 binding factors in nuclear extracts of the cerebral cortex, hippocampus and cerebellum 15 and 17 hr after withdrawal. These data reveal a complex pattern of immediate early gene expression during ethanol withdrawal, which may be associated with changes in neuronal plasticity underlying phenomena such as withdrawal kindling.

Animals↗

PubMed1990

Acute administration of ethanol suppresses pentylenetetrazole-induced c-fos expression in rat brain.

The effect of acute ethanol administration on pentylenetetrazole-induced c-fos expression in rat brain was studied. Pentylenetetrazole induced the rapid and transient expression of c-fos mRNA in rat brain. Maximal induction at a dose of 30 mg/kg was detected within 30 min and persisted for 60 min. Thereafter c-fos gene expression decreased to control levels by 180 min. No increase in c-fos mRNA was evident at doses of pentylenetetrazole less than or equal to 20 mg/kg, whereas maximal elevation was seen at 30 to 40 mg/kg. This action was inhibited by acute ethanol treatment (blood alcohol level greater than or equal to 100 mg/dl). Acute ethanol treatment alone had no effect on c-fos gene expression.

Actins↗

PubMed1990

Ethanol and synaptosomal calcium homeostasis.

The effect of ethanol on synaptosomal calcium homeostasis was studied in the rat using the fluorescent dye, fura-2, and 45Ca uptake. The mitochondrial poison, cyanide, caused a substantial rise in intracellular free Ca2+ concentration, [Ca2+]i, over that of control synaptosomes. This rise was enhanced by ethanol. Ethanol also augmented the rise in [Ca2+]i induced by ouabain, indicating that modulation of Na(+)-Ca2+ exchange is probably not the underlying mechanism. The Ca2+ channel blockers, verapamil and La3+, also failed to inhibit the rise in [Ca2+]i caused by ethanol. Preincubation of synaptosomes with caffeine, however, caused a significant decrease in the rise of [Ca2+]i due to ethanol, suggesting that ethanol exerts effects on Ca2+ homeostasis at the level of the endoplasmic reticulum.

Animals↗

PubMed1988

Ethanol increases synaptosomal free calcium concentration.

The effect of ethanol on synaptosomal free calcium concentration [( Ca2+]i) and 45Ca2+ uptake was studied in vitro. Synaptosomes were prepared from forebrains of adult rats and incubated in the presence of ethanol 50-500 mM. [Ca2+]i determined by means of the Ca2+-sensitive dye, fura-2, was increased by ethanol in polarized and depolarized synaptosomes, whereas 45Ca2+ uptake was decreased. The results suggest that ethanol may influence neuronal calcium homeostasis by increasing rather than decreasing [Ca2+]i.

Animals↗

PubMed1987

The reaction of acetaldehyde with brain microtubular proteins: formation of stable adducts and inhibition of polymerization.

Stable adducts were formed by treatment of bovine brain microtubular proteins (MTP) with acetaldehyde, followed by gel filtration to remove excess acetaldehyde. The extent of stable adduct formation was determined using [14C]acetaldehyde and was correlated with acetaldehyde concentration and reaction time. Significant inhibition of MTP polymerization was observed at adduct concentrations of 0.6 mol acetaldehyde/mol tubulin dimer. The data suggest that repeated exposure of MTP to low concentrations of acetaldehyde, as would occur in the brain and other tissues of alcoholics, may inhibit MTP polymerization with neurological consequences.

Acetaldehyde↗

PubMed1987

Effects of acetaldehyde on polymerization of microtubule proteins.

The in vitro effects of ethanol and acetaldehyde on polymerization of calf brain microtubular proteins (MTP) were examined. While ethanol up to 100 mM had no effect on the polymerization of MTP, acetaldehyde above 0.5 mM had an inhibitory effect. This effect was not dependent on the presence of microtubule-associated proteins (MAPs), since acetaldehyde had a similar effect on the polymerization of highly purified tubulin. Electron microscopy revealed that the number and the length of microtubules at equilibrium was reduced by the presence of acetaldehyde. Acetaldehyde raised the critical concentration for tubulin assembly and caused greater inhibition at lower tubulin concentrations. Acetaldehyde augmented the depolymerizing effects of Ca2+ on preassembled microtubules. In addition, acetaldehyde itself caused depolymerization of microtubules but only in the absence of MAPs. Long-term (19.5 h) incubation of MTP with acetaldehyde led to significant loss of polymerization ability which could not be reversed by removal of acetaldehyde. This loss of activity was apparently independent of the observed formation of reducible adducts between acetaldehyde and MTP.

Acetaldehyde↗

PubMed1985

Ethanol tolerance and enhanced calcium/calmodulin-dependent phosphorylation of synaptic membrane proteins.

The chronic effects of ethanol on synaptic membrane proteins was studied in ethanol-tolerant rats. Synaptic plasma membranes and postsynaptic densities were prepared from homogenates of forebrain and incubated in vitro with [gamma-32P]adenosine triphosphate in the presence and absence of calcium and calmodulin. In ethanol-tolerant animals, enhanced phosphorylation of synaptic plasma membrane but not postsynaptic density proteins was demonstrated in the presence of calcium and calmodulin. These results suggest that the development of tolerance to ethanol may involve alteration in neuronal sensitivity to calcium.

Animals↗

PubMed1984

Neuropharmacology of delta-aminolaevulinic acid. II. Effect of chronic administration in mice.

delta-Aminolaevulinic acid (ALA) is suspected of being responsible for the neuropsychiatric symptoms of acute porphyria. The object of this study was to examine the effects of continuous administration of ALA in vivo on behaviour known to be affected in acute porphyria. ALA was administered to mice via minipumps implanted subcutaneously. Mean urinary excretion of ALA over the ensuing 7 days was approximately 80 mumol/kg b. wt./day. No significant effects on locomotor activity, motor co-ordination and grip and noci-perception were noted. These results do not support the hypothesis that chronic exposure of animals to ALA may produce a porphyria-like syndrome.

Aminolevulinic Acid↗