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K J Anderson

Publications and source records attributed to K J Anderson.

At least 37 records · Page 2Linked to original sources
PubMed1997

Neurochemical basis of disruption of hippocampal long term potentiation by chronic alcohol exposure.

The aim of this review is to summarize the possible mechanisms underlying the long-term impairment of learning and memory resulting from chronic ethanol treatment (CET) especially that involving decrements in long-term potentiation (LTP) in hippocampus. CET for a 28-week duration affects the rat hippocampal formation in such a way as to decrease the magnitude of LTP; an effect that can last as long as 7 months after ethanol withdrawal. It appears that NMDA receptor number in hippocampus is unchanged after CET whereas the data suggest a more pronounced role for changes in GABAergic and cholinergic synaptic transmission in determining how CET influences the induction of LTP in hippocampus. In particular, changes in presynaptic modulation of neurotransmitter release in hippocampus may be one mechanism by which CET inhibits LTP. Thus, the mechanisms underlying the effect of CET on LTP are a result of changes in a number of neurotransmitter systems in hippocampus (GABAergic and cholinergic) rather than based solely on changes in glutamate transmission.

Acetylcholine↗
PubMed1997

Effects of chronic ethanol exposure on GABA receptors and GABAB receptor modulation of 3H-GABA release in the hippocampus.

Chronic ethanol treatment (CET), sufficient for decreasing long-term potentiation (LTP) in rats, also enhances 3H-GABA release from hippocampal slices in these same animals. The mechanism for an increase in GABA release may involve changes in presynaptic receptors. Therefore, we characterized presynaptic autoreceptor modulation of 3H-GABA release in hippocampal slices from control and CET rats. The effects of a GABAB receptor agonist (baclofen) and antagonist [2-hydroxy (OH)-saclofen] were tested for their ability to modulate electrically stimulated 3H-GABA release from superfused hippocampal slices. Baclofen decreased stimulated release in a dose-dependent manner and 2-OH-saclofen increased release consistent with the existence of presynaptic GABAB autoreceptors in hippocampus. The GABAA antagonist bicuculline did not significantly modulate basal or stimulated release. When the effects of baclofen and 2-OH-saclofen were measured in animals 48 hr after withdrawal from CET, presynaptic modulation of release by baclofen and 2-OH-saclofen was decreased. In addition, we examined the density of 3H-baclofen and 3H-bicuculline binding in the hippocampal formation using quantitative autoradiographic techniques. We found that the density of 3H-baclofen binding sites was not affected by CET, whereas the density of 3H-bicuculline binding sites was increased by 28% in ethanol-treated rats. These data may explain how CET increases presynaptic regulation of GABA release from hippocampus that may contribute to the decrease in LTP seen in rats after CET.

Alcoholism↗
PubMed1996

Distribution of heterotopic neurons in normal hemispheric white matter: a morphometric analysis.

One of the frequent abnormalities described in the context of surgically resected temporal lobe (TL) specimens is the presence of heterotopic neurons within white matter (WM). We have attempted to morphometrically define the distribution of the heterotopic neurons in normal subjects, comparing the incidence of heterotopic neurons in TL WM with that in occipital (OL) and frontal lobe (FL) sections. Using a a combination of routine and special stains combined with immunohistochemical confirmation 20 adult autopsy cases were examined. WM from TL, FL, and Ol sections was outlined and the area measured by image analysis. Using defined criteria, heterotopic neurons within these areas were counted. Results confirm our hypothesis that normal adult TL WM contains a significantly higher population of residual/heterotopic neurons than OL and FL WM groups. It is felt that these neurons represent interstitial remnants of the subplate which have failed to undergo programmed cell death. The significance of these findings with regard to assessment of similar findings in temporal lobectomy specimens is addressed. A second intriguing association of this TL WM heterotopia concerns its possible relationship to the more frequent occurrence of ¿malformative neoplasms¿ with neuronal elements (such as ganglioglioma and dysembryoplastic neuroepithelial tumor) in the temporal lobe.

Adult↗
PubMed1996

Glutamate receptors in the frontal cortex of alcoholics.

This study tests the hypothesis that glutamate receptors are altered in the brains of alcoholics as a result of chronic alcohol neurotoxicity. Release of the neurotransmitter glutamate after seizures or brain ischemia may damage postsynaptic neurons by increasing calcium flux through N-methyl-D-aspartate (NMDA) receptor-gated ion channels. Alcohol has two opposite effects on glutamate receptor ion channel complexes, depending upon the duration of exposure. Acute exposure to alcohol inhibits ion flow through these receptor-channel complexes, whereas chronic exposure up-regulates the number of these receptors and thereby increases ion flow. Acute withdrawal from alcohol results in hyperexcitability and seizures in the presence of up-regulated channels, thereby making postsynaptic neurons vulnerable to excitotoxic damage. We selected 13 histologically normal brains from alcoholics and 13 brains from controls from our brain bank that were matched for age, postmortem interval, and storage time. Maximal binding and affinities of glutamate receptor subtypes were determined by quantitative autoradiography in the superior frontal cortex, Brodmann area 8. The most alcohol-sensitive subtype, NMDA receptor-channel complexes, were modestly but consistently increased in alcoholics. This included agonist sites (NMDA-sensitive [3H]glutamate), and antagonist site ([3H]CGP-39653), and a [3H]MK-801 binding site in the channel interior, although the increase of the latter did not reach statistical significance. Age, autopsy delay, time in storage, liver diseases, thiamine deficiency, CNS medications, and various diseases causing acute and chronic hypoxia did not significantly affect receptor density or affinity. In contrast, the other two glutamate channel subtypes, AMPA and kainate receptors, were not significantly different in alcoholics compared with controls. In conclusion, chronic alcoholism moderately increases the density of the NMDA subtype of glutamate receptors in the frontal cortex. This up-regulation may represent a stage of alcohol-induced chronic neurotoxicity.

Aged↗
PubMed1996

Long-term effects of chronic ethanol on muscarinic receptor binding in rat brain.

Effects of chronic ethanol treatment (CET) on muscarinic acetylcholine receptor (mAChR) binding properties were investigated via quantitative autoradiography in rats maintained on an ethanol-containing liquid diet for 28 weeks and withdrawn from ethanol for 8 weeks before harvesting of tissues. Controls received an identical diet in which sucrose was substituted isocalorically for ethanol. Maximal binding of the radiolabeled mAChR antagonist quinuclidinyl benzilate ([3H]QNB) was not reduced in hippocampal area CA1, dentate gyrus, neocortex, striatum, or thalamus, suggesting that CET results in no significant mAChR loss in these regions. Binding affinities of the cholinergic agonist carbachol to mAChRs were unaffected by CET in each of these regions, as determined by competitive displacement of [3H]QNB labeling. These results suggest that CET-induced functional deficits in brain cholinergic responses are not due to direct effects of CET on mAChR binding properties.

Animals↗
PubMed1996

Characterization and distribution of the neuronal glutamate transporter EAAC1 in rat brain.

The extracellular concentration of glutamate and other related excitatory amino acids (EAA) is regulated by the action of transporter proteins located on either presynaptic terminals or adjacent astroglial processes. Recent molecular advances have led to the cloning of three separate cDNAs encoding for Na(+)-dependent glutamate transporters; two are thought to be primarily glial in origin (GLAST and GLT-1) and the third (EAAC1) is localized to neurons in the brain and other nonneural tissues. An EAAC1 cDNA was initially cloned from rabbit small intestine (13). In this study, we report isolation and characterization of the homologous clone from rat brain. Northern blot hybridization revealed high levels of EAAC1 mRNA in rat brain and kidney and low levels in heart, lung, and skeletal muscle. Transient expression of EAAC1 in HeLa cells resulted in an increase in Na(+)-dependent high-affinity L-[3H]glutamate and D-[3H]aspartate transport. The pharmacological profile of EAAC1 was very similar to that reported for the rabbit and human EAAC1 homologues. Transport activity was potently inhibited by D- and L-threo-beta-hydroxyaspartate and L-trans-pyrrolodine-2,4-dicarboxylate. Dihydrokainate and L-alpha-aminoadipate did not inhibit transport at concentrations below 1 mM. Oligonucleotide cDNA probes (45-mer) were constructed and labeled with 35S-ATP for film- and emulsion-based in situ hybridization of rat brain. EAAC1 mRNA had the highest density in the cerebellar granule cell layer, hippocampus, superior colliculus, and neocortex. Sections that were emulsion-dipped and counterstained with cresyl violet revealed EAAC1 labeling localized exclusively over neuronal cell bodies, including some nonglutamatergic neurons such as spinal cord ventral horn cells.

Amino Acid Sequence↗
PubMed1996

Estimation of variance components and prediction of breeding values for scrotal circumference and weaning weight in Limousin cattle.

Variance and covariance components were estimated for yearling scrotal circumference and weaning weight from Limousin field data. Records of 8.226 bulls were used to evaluate 584 sires and 653 maternal grandsires. Data included all herdbook records of bulls with a recorded scrotal circumference and their weaning contemporaries. Analyses were performed by restricted maximum likelihood techniques employing the expected maximization algorithm and fitting both single- and two-trait models. Scrotal circumference was first fitted in a single-trait, sire model to obtain starting values for variances for a later analysis. Likewise, weaning weight was fitted in a single-trait, sire-maternal grandsire model to obtain priors for (co)variances for a later analysis. Scrotal circumference and weaning weight were then fitted together in a two-trait model to estimate variance components. Estimates of variance components were calculated by equating (co)variances obtained from the models to their expectations. Estimates of heritability of scrotal circumference, direct weaning weight, and maternal weaning weight were .46, .25, and .19, respectively. Estimates of genetic correlations between yearling scrotal circumference and direct weaning weight, scrotal circumference and maternal weaning weight, and direct weaning weight and maternal weaning weight were .14, -.22, and -.44, respectively. The estimate of the environmental correlation between scrotal circumference and weaning weight was .61. Genetic parameters obtained were then used in two-trait, reduced animal mixed-model equations for a maternally influenced trait to predict breeding values for animals.

Algorithms↗
PubMed1995

The long-term effectiveness of a radiology memorandum.

RATIONALE AND OBJECTIVES: This informal prospective study was designed to document the long-term effectiveness of a radiology department policy memorandum as a communication tool. A memorandum outlining the departmental policy regarding radiographic imaging of pregnant or possibly pregnant patients served as the study model. METHODS: A departmental obstetric policy memorandum was distributed to all radiology personnel, including faculty and residents. The effectiveness of the memorandum was measured by the ability of all department personnel to answer specific test questions about the policy 1 year after its distribution. RESULTS: Nine (41%) in the faculty/fellow group and seven (41%) residents gave partially correct answers about policy content. There were no totally correct policy content answers in either group. Thirty-eight (64%) of the technology staff knew the entire policy content. CONCLUSION: Staff radiologists, fellows, and residents demonstrated an unacceptable level of knowledge concerning the policy content and location. Technologists, technology students, and clerks demonstrated a more acceptable level of knowledge of the policy than did radiologists. A single memorandum without repetition or constant surveillance is not an effective communication tool to alert radiologists to the importance of understanding and implementing policy directives.

Clinical Competence↗
PubMed1994

Impulsivity and time of day: is rate of change in arousal a function of impulsivity?

Impulsivity has been interpreted as a stable mediator of rate of change in arousal states. To test this hypothesis, 129 Ss differing in impulsivity were given placebo or caffeine at 9:00 a.m. or 7:30 p.m. Recognition memory was tested for the last 20 items from 2 lists of 24 items and 2 lists of 80 items. Scores from this paradigm reflect sustained attention and are thus sensitive to changes in arousal. A 4-way interaction among impulsivity, time of day, drug, and prior stimuli (p < .05) indicated that for those given placebo, recognition memory for long and late lists was poorer the higher the impulsivity in the morning; this pattern reversed in the evening. Caffeine reduced recognition errors. These results indicate that impulsivity is not a stable predictor of rate of change in arousal states. Instead, susceptibility to attentional lapses is mediated by impulsivity-related phase differences in diurnal arousal rhythms.

Arousal↗
PubMed1994

Stability of [3H]MK-801 binding sites following chronic ethanol consumption.

Previous work has demonstrated that short periods (1-2 weeks) of exposure to ethanol produce an upregulation of the N-methyl-D-aspartate (NMDA) receptor complex in hippocampus; an alteration that appears to be associated with the development of physical dependence, because a return to control levels occurs over a 24- to 48-hr abstinence period. Prolonged periods of chronic ethanol treatment (CET; 4-8 months of treatment) have been shown to produce severe and permanent alterations in the morphological and functional characteristics of hippocampal pyramidal neurons. Several lines of research have demonstrated that the NMDA receptor complex is involved in excitotoxic cell loss during certain pathological states. On the basis of this evidence, we hypothesized that prolonged ethanol exposure would be accompanied by an enduring increase in NMDA receptors and that NMDA receptor binding in cells surviving CET would be altered. To test this hypothesis, we measured the binding characteristics of the NMDA receptor complex in a variety of brain structures following CET. Animals were fed a nutritionally complete, ethanol-containing diet for 28 weeks and then allowed a 48-hr abstinence period. A control group was fed the same diet, except sucrose was isocalorically substituted for ethanol. We first examined the effect of CET on the binding properties of a noncompetitive antagonist to the NMDA receptor channel, [3H]diclozipene ([3H]MK-801). Next, as an indirect examination of NMDA receptor function, we measured the ability of glutamate to stimulate channel opening and thus [3H]MK-801 binding. In all brain structures examined, neither the Kd nor the Bmax of [3H]MK-801 binding to the NMDA receptor was altered following CET. In addition, no effect of treatment was seen on the ability of glutamate to stimulate [3H]MK-801 binding.

Alcoholism↗
PubMed1993

Ischemia-induced upregulation of excitatory amino acid transport sites.

The response of excitatory amino acid transporter binding sites in the rat brain to 10 min of cerebral ischemia induced by bilateral common carotid occlusion combined with hypotension was examined. We observed a transient increase in the density of transporter binding sites that was first noticeable at 5 min post-recovery and persisted for 48 h. The increase in binding sites was found throughout the brain, but was most prevalent in hippocampus and other cortical regions. We conclude that delayed neuronal death following transient cerebral ischemia may not be due to a decrease in the number of excitatory amino acid transport sites.

Animals↗
PubMed1993

Autoradiography of L-[3H]aspartate binding sites.

The distribution, pharmacology and binding properties of L-[3H]aspartate were determined in sections from rat brain. No binding was detected in the absence of sodium ions. With the addition of sodium ions to the incubation medium, binding was found to be NMDA, AMPA and CNQX insensitive, but was potently inhibited by threo-beta-hydroxyaspartate, D-aspartate and L-2,4 trans-pyrrolidine dicarboxylate; compounds which have been shown to be specific inhibitors of the sodium-dependent EAA transporter. Autoradiography of L-[3H]aspartate closely resembled the pattern of sodium-dependent D-[3H]aspartate binding. Cerebellar binding showed higher affinity and maximal levels of binding than forebrain, consistent with reports of heterogeneous populations of sodium-dependent EAA binding sites. These results suggest that under these conditions, L-[3H]aspartate specifically labels the sodium-dependent EAA transporter.

Amino Acid Transport Systems↗
PubMed1991

Increased density of excitatory amino acid transport sites in the hippocampal formation following an entorhinal lesion.

High affinity transport of excitatory amino acids such as L-glutamate into astrocytes is necessary for the termination of its excitatory signal and the prevention of its excitotoxic effects. The removal of glutamate from the synaptic cleft is carried out by both sodium- and chloride-dependent systems. Both sodium-dependent D-[3H]aspartate and chloride-dependent L-[3H]glutamate binding were found to increase in the dentate gyrus molecular layer of rats following an entorhinal lesion. The increased binding reached a maximum at 5 and 7 days postlesion and returned to normal by 12 days postlesion. No changes in binding were observed at long time points postlesion. This increased ability to transport glutamate may be a compensatory response to protect the remaining neurons from the excitotoxic conditions that accompany neuronal degeneration.

Animals↗
PubMed1991

Quantitative autoradiographic analysis of excitatory amino acid receptors in the cat spinal cord.

Using quantitative autoradiography, we have studied the density and distribution of N-methyl-D-aspartate (NMDA), kainate and AMPA receptors and the binding site for the sodium-dependent EAA transporter in sections from the cat spinal cord. NMDA, kainate and AMPA receptors were found in highest concentrations in laminae I and II of the dorsal horn. Lower levels of all receptors were seen in other regions of the spinal cord grey matter. The distribution of the sodium-dependent transporter was unlike that of any of the receptor populations with highest levels found in the ventral horn with slightly lower levels in other regions of grey matter. The pattern of binding sites was consistent throughout all levels of the spinal cord.

Animals↗
PubMed1991

Astrocyte hypertrophy in the Alzheimer's disease hippocampal formation.

In Alzheimer's disease (AD), neuritic plaques are often found in the hippocampal dentate gyrus along the boundary between inner and outer molecular layers. The dentate outer molecular layer in AD also exhibits axon sprouting in response to an early loss of entorhinal neurons. The relationship between the laminar arrangement of plaques and the sprouting remains unclear. In experimental entorhinal lesions in the rat, the denervated dentate outer molecular layer demonstrates hypertrophic astrocytes which may provide trophic support for the sprouting response. It is not known whether an equivalent astrocyte response occurs in AD or whether this response is related to the distribution of plaques. We used immunohistochemical staining for glial fibrillary acidic protein (GFAP) to demonstrate reactive astrocytes in the hippocampus in AD patients and age-matched controls. These results were compared to the astrocyte response to an experimental entorhinal lesion in the rat. Quantitative and qualitative analyses demonstrated a significant increase in GFAP-positive hypertrophic astrocytes in the dentate outer molecular layer in AD compared to controls. These astrocytes were randomly distributed within the outer layer and did not parallel the distribution of neuritic plaques. In the entorhinal-lesioned rat, reactive hypertrophied astrocytes also showed a selective distribution within the denervated outer molecular layer. Our results further support the similarity of the hippocampal response in AD and experimental entorhinal lesion but do not explain the laminar distribution of neuritic plaques along the denervated zone.

Alzheimer Disease↗