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B Ault

Publications and source records attributed to B Ault.

14 recordsLinked to original sources
PubMed1992

NMDA receptor-mediated depolarizing action of proline on CA1 pyramidal cells.

This study investigated the actions of proline on CA1 hippocampal pyramidal cells with use of slice preparations. Bath-applied L-proline first induced these cells to fire multiple orthodromic population spikes in response to a single stimulus and then blocked their response to both orthodromic and antidromic stimulation. These effects could be explained by postsynaptic depolarization followed by depolarization block. Grease-gap studies confirmed that L-proline depolarizes CA1 pyramidal cells. D-Proline was inactive in these tests. Excitatory amino acid antagonists reduced depolarizing responses to proline and N-methyl-D-aspartate (NMDA) in parallel. Mn2+ failed to attenuate proline-evoked depolarizations at concentrations that substantially inhibited synaptic transmission, but at a higher concentration it reduced responses to both proline and NMDA. These results suggest that proline depolarized CA1 pyramidal cells mainly by activating postsynaptic NMDA receptors. The neuroexcitatory and neurotoxic actions of proline in the hippocampus may contribute to the seizures and mental retardation associated with hyperprolinemia.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1992

cis and trans elements differ among mouse strains with high and low extrahepatic complement factor B gene expression.

Factor B (Bf), an enzyme of the alternative pathway of complement activation, is one of four major histocompatibility complex (MHC) class III genes. To ascertain the genetic mechanism for tissue-specific constitutive and regulated expression of Bf, we sequenced the regulatory regions 5' of the gene from mice of different H-2 MHC haplotypes and assessed trans-acting factors, specific DNA binding nucleoproteins, in liver and kidney. Striking tissue-specific differences in constitutive expression of Bf were demonstrated in mice of H-2f or H-2z haplotypes when compared with H-2d or H-2u (kidney and intestinal Bf in H-2d or H-2u much greater than H-2f or H-2z). These differences correlated with a point nucleotide substitution 3 bp downstream of the upstream Bf initiation site that affects interaction with a DNA binding protein. This and additional cis differences localize the sequence substitutions responsible for previously identified restriction fragment length polymorphisms among inbred mouse strains and also reveal two previously unrecognized polymorphisms generated by SmaI and HinfI digestion. Evidence for differences in trans was found in a comparison of DNA binding nucleoproteins from kidney, but not liver, of B10.PL when compared with B10.M. These data, together with the high degree of sequence homology between human and mouse Bf 5' flanking regions, should prompt a search for polymorphic restriction sites and cis binding elements in the Bf promoter that could serve as markers of human MHC-associated renal pathology and variants in local MHC class III gene expression.

Animals↗
PubMed1991

Effects of nerve growth factor on electrical membrane properties of cultured dorsal root ganglia neurons from normal and trisomy 21 human fetuses.

Trisomy 21 (Down syndrome) results in abnormalities of electrical membrane properties of cultured human fetal dorsal root ganglion (DRG) neurons; namely, faster rates of depolarization and repolarization of the action potential, and a shortened spike duration. A possible role of nerve growth factor (NGF) in the expression of abnormal electrical membrane properties fetal human DRG neurons from trisomy 21 subjects was examined. DRG neurons obtained from normal and trisomy 21 abortuses of 16-20 weeks gestation were cultured in the presence or absence of 40 nM 7S NGF. After 1 week in culture, action potentials were recorded using the whole cell patch-clamp technique, in current clamp mode. At the resting membrane potential, normal (diploid) neurons grown without NGF showed reduced maximal rates of depolarization (-41.3%) and of repolarization (-31.4%), a decreased spike amplitude (-14.2%) and a prolonged action potential (+49.2%), when compared to normal cells cultured with NGF. Trisomy 21 neurons showed similar changes, but had a greater relative decrease in the rates of action potential depolarization and repolarization. These changes were evident at different membrane potentials. Normal and trisomic DRG neurons cultured without NGF showed differences in action potential parameters similar to those previously described using NGF-supplemented culture medium. These data indicate that NGF can regulate electrical membrane properties in cultured human fetal DRG neurons, but apparently is not responsible for the abnormalities observed in trisomy 21 neurons.

Action Potentials↗
PubMed1991

Mouse trisomy 16 neurons, a model of human trisomy 21 (Down syndrome), can be maintained by intracerebral transplantation.

The trisomy 16 mouse is considered to be a model of human trisomy 21 (Down syndrome) due to genetic homology between parts of human chromosome 21 and mouse chromosome 16. Additionally, and because older Down syndrome individuals develop neuropathology indistinguishable from that of Alzheimer's disease, trisomy 16 tissue may provide a model of some pathological processes occurring in Alzheimer's disease. However, trisomy 16 fetuses die in utero or shortly after birth, preventing exploitation of this model. We therefore sought to examine trisomy 16 brain tissue over an extended period of time. We report that neural transplantation to normal hosts allows the maintenance of cortical and hippocampal neurons for at least 8 months, thus providing a model in which to examine pathological processes related to Down syndrome, and perhaps to Alzheimer's disease.

Animals↗
PubMed1990

Electrical membrane properties of cultured dorsal root ganglion neurons from trisomy 19 mouse fetuses: a comparison with the trisomy 16 mouse fetus, a model for Down syndrome.

Because of synteny between mouse chromosome 16 and human chromosome 21, murine trisomy 16 (Ts16) has been considered an animal model for Down syndrome. Indeed, previous investigations have demonstrated that action potentials of cultured dorsal root ganglion (DRG) neurons from human trisomy 21 (Down syndrome) or mouse Ts16 fetuses show increased depolarization and repolarization rates, and decreased spike duration, compared to control neurons. In order to determine the specificity of these changes, we studied the electrical membrane properties of DRG neurons in culture from trisomy 19 (Ts19) and control fetal mice, using the whole cell patch-pipette recording technique. We found no significant differences in action potential parameters and passive membrane properties between Ts19 and control neurons. These findings support the notion that the alterations previously reported in Ts16 DRG neurons are specific, and not a general consequence of genetic imbalance imposed by autosomal trisomies.

Action Potentials↗
PubMed1990

The role of altered sodium currents in action potential abnormalities of cultured dorsal root ganglion neurons from trisomy 21 (Down syndrome) human fetuses.

Trisomy 21 (Down syndrome) results in abnormalities in electrical membrane properties of cultured human fetal dorsal root ganglion (DRG) neurons. Action potentials have faster rates of depolarization and repolarization, with decreased spike duration, compared to diploid neurons. In order to analyze the faster depolarization rate observed in trisomic neurons, we examined sodium currents of cultured human fetal DRG neurons from trisomy 21 and control subjects, using the whole-cell patch-clamp technique. The neurons were replated in culture to reduce dendritic spines. Two components of the sodium current were identified: (1) a fast, tetrodotoxin (TTX)-sensitive current; and (2) a slow, TTX-resistant component. The inactivation curves of both current types in trisomic neurons showed a shift of approximately 10 mV towards more depolarized potentials compared to control neurons. Thus, whereas essentially all of the fast sodium channels were inactivated at normal resting potentials in control neurons, approximately 10% of these channels were available for activation in trisomy 21 cells. Furthermore, the fast current showed accelerated activation kinetics in trisomic neurons. The slow sodium current of trisomic neurons showed slower deactivation kinetics than control cells. No differences were observed between trisomic and control neurons in the maximal conductance or current densities of either fast or slow current components. These data indicate that the greater rate of depolarization in trisomy 21 neurons at resting potentials is primarily due to activation of residual fast sodium channels that also have a faster time course of activation.

Action Potentials↗
PubMed1990

Replating improves whole cell voltage clamp recording of human fetal dorsal root ganglion neurons.

The whole cell patch clamp technique allows recording of membrane currents in an entire cell under voltage clamp conditions. However, technical difficulties arise in large cells bearing extensive processes, such as human fetal dorsal root ganglion (DRG) neurons in culture. In order to improve space clamp conditions, human fetal DRG neurons cultured for 1-2 weeks were enzymatically detached and replaced in new dishes, yielding round or oval cells with absent or short processes at 24 h in culture. Current clamp recordings demonstrated no difference in action potential parameters of the replated cells compared to control non-replated cells. Analysis of passive properties showed a reduction of 40% in mean specific membrane capacitance and a 57% increase in mean specific membrane resistance in the replated cells, consistent with the decrease of cell membrane surface area. Whole cell voltage clamp studies demonstrated great improvement of the space clamp, indicating that more efficient voltage clamp conditions can be achieved in neurons in culture by eliminating neurites through replating.

Down Syndrome↗
PubMed1989

Electrophysiological analysis of cultured fetal mouse dorsal root ganglion neurons transgenic for human superoxide dismutase-1, a gene in the Down syndrome region of chromosome 21.

Our recent whole cell patch-pipette studies have shown that human trisomy 21 (Down syndrome) cultured fetal dorsal root ganglion (DRG) neurons have accelerated rates of action potential depolarization and repolarization, with reduced spike duration, compared to control neurons. Similar observations were made using DRG neurons from the trisomy 16 mouse, an animal model of trisomy 21. In this study we have used transgenic mice in order to investigate the relationship between excess gene dosage and neurophysiological abnormalities. DRG neurons which possessed additional copies of the gene for human superoxide dismutase-1 (SOD), a gene from the Down syndrome region of chromosome 21, were compared to normal neurons. No electrophysiological differences were found between the two groups of neurons, indicating that increased dosage of the SOD gene alone is not causal to action potential dysfunction found in trisomy 21 and trisomy 16 neurons.

Animals↗
PubMed1989

Neurophysiological abnormalities in cultured dorsal root ganglion neurons from the trisomy-16 mouse fetus, a model for Down syndrome.

The trisomy-16 mouse is considered to be a model of human trisomy-21 (Down syndrome). We have examined the electrical membrane properties of cultured dorsal root ganglion (DRG) neurons from normal and trisomy-16 fetuses. Trisomy-16 neurons had significantly accelerated rates of action potential depolarization and repolarization compared to diploid neurons, resulting in decreased spike duration. These changes match those reported in human trisomy-21 DRG neurons. Such abnormalities may contribute to the mental retardation characteristic of Down syndrome.

Action Potentials↗
PubMed1986

Baclofen suppresses bursting activity induced in hippocampal slices by differing convulsant treatments.

Epileptiform activity was induced in area CA3 of hippocampal slices by superfusion of medium containing 50 microM bicuculline and 3.5 mM K, 50 microM bicuculline and 5 mM K, 50 nM kainic acid and 3.5 mM K, or 7 mM K. Burst potentials were recorded at rates between 5 and 44/min, depending on the convulsant treatment. Baclofen reduced the frequency of burst firing in all slices tested in a dose-dependent manner, with little change in the morphology of individual bursts. Thus baclofen primarily affected the initiation of epileptiform discharges. IC50 values varied between 27 and 500 nM and were positively correlated with the rate of bursting. These experiments indicate that baclofen, at concentrations present in the CSF of patients treated for spasticity, has an anticonvulsant-like effect in the hippocampal formation and suggest that its mode of action is to reduce the excitability of pyramidal cells.

Action Potentials↗
PubMed1986

Adenosine inhibits epileptiform activity arising in hippocampal area CA3.

The ability of adenosine and structurally-related compounds to inhibit epileptiform activity induced by bicuculline in the CA3 region of the hippocampal slice of the rat was examined. Bath application of all purinoceptor agonists tested reduced the frequency of generation of burst potentials. Analysis of dose-response curves yielded the following IC50 values: adenosine, 1.5 microM; 2-chloroadenosine, 0.144 microM; 5'-(N-ethyl)carboxamidoadenosine, 30.2 nM; L-phenylisopropyladenosine, 12.1 nM; cyclohexyladenosine, 7.9 nM. Theophylline (30 microM) increased the rate of bursting and antagonized the effect of exogenous adenosine. Dipyridamole (0.03-1 microM) reduced the occurrence of burst firing. In slices untreated with bicuculline, theophylline (30 microM) and adenosine deaminase (10 micrograms ml-1) induced bursting activity. These results demonstrate that purinoceptor agonists can suppress epileptiform activity in the hippocampus and suggest that adenosine may act as an endogenous anticonvulsant.

Adenosine↗
PubMed1986

Baclofen suppresses hippocampal epileptiform activity at low concentrations without suppressing synaptic transmission.

Baclofen is used clinically to treat spasticity, but has received little attention as a potential antiepileptic agent. To explore the antiepileptic potential of baclofen further, we tested its effect on stimulus train-induced bursting, an in vitro model of hippocampal epileptiform activity. In hippocampal slices prepared from male rats, extracellular field potentials were recorded in stratum pyramidale of CA3, and electrical stimuli were delivered to s. radiatum of CA3. After stable responses to single stimuli were established, stimulus trains were delivered every 5 min until stable triggered and spontaneous population bursting were elicited. (+/-)-Baclofen was bath-applied to the slices at varying concentrations to study its ability to suppress synaptic transmission and epileptiform activity. EC50 values for suppression of orthodromic population spike amplitude, of triggered burst duration and of spontaneous burst frequency were 2300, 355 and 26.9 nM, respectively; all statistically significantly different. These findings suggest that baclofen suppresses epileptiform electrical activity in the hippocampus at concentrations well below those which suppress normal synaptic transmission, and support renewed consideration of baclofen as an antiepileptic agent.

Animals↗