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Biomedical subjects

T I Lidsky

Publications and source records attributed to T I Lidsky.

At least 19 recordsLinked to original sources
PubMed2006

Adverse effects of childhood lead poisoning: the clinical neuropsychological perspective.

Elevated blood lead levels in children can result in brain injury and, as a consequence, have negative effects on cognitive functioning and behavior. Risk assessment studies have focused on psychological measures, especially IQ, and also school achievement and behavioral adjustment as endpoints. Such studies, like epidemiological work in other areas, by necessity examine effects in large groups rather than in individuals. Since the peer-reviewed literature primarily describes those adverse effects noted in epidemiological studies, little or no attention has been directed to what is observed in the individual. The present review describes the presentation of individual lead-poisoned children from the perspective of the clinical neuropsychologist. The sequelae of lead poisoning typically observed in evaluation of individuals provide information in addition to that gained from risk assessment studies and has implications for the mechanisms and treatment of this disease. In addition, attention to certain aspects of individual case presentation does provide information relevant to issues of public health.

Child↗
PubMed2005

Inhibition of progenitor cell proliferation in the dentate gyrus of rats following post-weaning lead exposure.

Although lead is a potent developmental neurotoxin, the effects of postnatal lead exposure on progenitor cell proliferation in the hippocampus has not been examined. Postnatal day 25 rats were fed a lead containing diet (1500 ppm lead acetate) for 30-35 days and administered bromodeoxyuridine (BrdU, 50 mg/kg, i.p.) during the last 5 days of lead exposure. Animals were killed 24 h after the last BrdU injection. Proliferation of new cells in the subgranular zone and dentate gyrus was significantly decreased in lead-exposed rats compared to control animals that ate a similar diet devoid of lead. These results suggest that postnatal lead exposure can have significant deleterious effects on progenitor cell proliferation and thus the structure and function of the hippocampus.

Animals↗
PubMed2001

Enriched environment during development is protective against lead-induced neurotoxicity.

It is known that children of lower socioeconomic status have a disproportionately higher risk of being exposed to lead and have a more negative outcome from that exposure than children who are raised under more fortunate circumstances. Yet, little is known about how environmental factors may influence the injurious effects on the brain of a neurotoxin such as lead. The present study used an animal model of lead poisoning to examine the extent to which different environmental milieus may modify the effects of lead on the developing brain. Young rats were raised in either enriched or impoverished environments and drank either distilled water or water with lead. Lead-exposed rats raised in the impoverished environment had spatial learning deficits and significantly decreased neurotrophic factor gene expression in the hippocampus. In contrast, the animals raised in the enriched environment were significantly protected against the behavioral and neurochemical toxicity of lead. These results demonstrate that impoverished environment may accentuate while enriched environment may ameliorate neurobehavioral and neurochemical toxicity from developmental lead exposure.

Animals↗
PubMed1999

Behavioural context and a distributed system: metabolic mapping studies of the basal ganglia.

Behavioural context is known to affect neural activity in the striatum. Responses of single cells increase to rewarding stimuli, or drop out as a bar press or saccade is learned. Networks that can accomplish a unique response to changing contexts are of particular interest to systems neuroscience and were a part of Hebb's interest in perception and learning. An overall map of the striatum that localizes changes related to this remarkable phenomenon of contextual responses contributes to our understanding of anatomical substrates of neural systems that integrate information, and may lead us to new striatal regions to study synaptic mechanisms of learning.

Afferent Pathways↗
PubMed1999

Persisting insomnia following traumatic brain injury.

Persisting insomnia secondary to traumatic brain injury, rarely reported and documented, is described in an adult male following head injury. The neuronal mechanisms underlying this sleep disorder as well as the neuropsychological concomitants and therapeutic approaches are discussed.

Adult↗
PubMed1998

Chronic neuroleptic treatment alters expression of glial glutamate transporter GLT-1 mRNA in the striatum.

Recent reports have shown that typical neuroleptics may enhance glutamatergic neurotransmission and that these effects might in part underlie motor side effects of chronic neuroleptic treatment. Since glutamate reuptake is the primary mechanism for controlling extracellular glutamate levels, the present study was conducted to examine whether chronic neuroleptic exposure alters gene expression for the glutamate transporter GLT-1 in the striatum. Although both haloperidol and clozapine treatment for 30 days significantly decreased GLT-1 expression from normal, the effects of haloperidol treatment were consistently, and in the dorsal striatum, significantly greater than those of clozapine. These findings suggest that a deficiency in glutamate transport may underlie the pathogenesis of neuroleptic-induced movement disorders.

ATP-Binding Cassette Transporters↗
PubMed1998

Persistent cognitive and motor deficits following acute hydrogen sulphide poisoning.

This case study describes the long-term after-effects of hydrogen sulphide exposure in a previously health 27-year-old male. Upon hospital admission the patient had a Glasgow Coma Score (CGS) of 3; with emergency treatment including hyperbaric oxygen treatments, he progressed to a GCS of 15 on day 7. Although both CT and MRI scans were unremarkable, PET using F-18 deoxyglucose administered 3 years after the accident showed abnormally decreased metabolism bilaterally in the temporal and inferior parietal lobes as well as the left thalamus. Uptake in the striatum was heterogeneous and abnormal. A cerebral perfusion study using SPECT performed 3.5 years after the accident revealed bilaterally decreased flow in the putamen but no cortical abnormalities. Neuropsychological and neurofunctional testing revealed the following impairments: microsmia, psychomotor slowing, extrapyramidal signs and deficits in memory and executive/planning functioning. These findings are discussed in the context of hydrogen sulphide's known mechanisms of toxicity and the functions of the basal ganglia.

Adult↗
PubMed1997

Antipsychotic drug effects on glutamatergic activity.

Previous work from this laboratory indicated that some antipsychotic drugs possess unique action at N-methyl-D-aspartate (NMDA) receptors. A functional neurochemical assay showed that, at concentrations similar to those found in the cerebrospinal fluid (CSF) of schizophrenics, antipsychotic drugs augment NMDA activity while, at higher concentrations, NMDA activity is suppressed. Using similar analysis, the present paper reports that this pattern of response is also shown by the antipsychotic drugs thioridazine and chlorpromazine. In contrast, promazine, which is structurally similar to chlorpromazine but lacking both D2-effects and antipsychotic potency, had no influence on NMDA receptors. In addition, sulpiride and metoclopramide, drugs with high affinity for D2-dopamine receptors but with weak or no antipsychotic efficacy, also lack effects at the NMDA receptor. Thus, the drugs with clinical efficacy that were tested in the present and previous studies all share unique influence on NMDA receptors. Further work with other antipsychotic agents will be necessary to determine if influence on NMDA receptors contributes to antipsychotic effectiveness.

Animals↗
PubMed1997

Sensory and cognitive functions of the basal ganglia.

Recent studies have found that the basal ganglia are involved in diverse behavioral activities and suggest that they have executive functions. Highlights from the past year include anatomical and clinical studies that have used sophisticated, novel methods to confirm a role for the basal ganglia in somatosensory discrimination, visual perception, spatial working memory and habit learning.

Animals↗
PubMed1995

Glutamate agonist activity: implications for antipsychotic drug action and schizophrenia.

Antagonist action at dopamine D2 receptors appears to explain many, but not all of the effects of antipsychotic drugs. Because of the interactions of dopamine with glutamate, and the implication of the latter in the etiology of schizophrenia, possible effects of antipsychotic drugs on glutamate receptors were assessed in the present experiments. These studies showed that, at clinically relevant concentrations, the conventional neuroleptic haloperidol and the atypical antipsychotic clozapine had potent augmenting influences on the NMDA receptor. These data suggest that unique action at glutamate receptors may contribute to antipsychotic efficacy and emphasize the potential importance of glutamatergic dysfunction in the etiology of schizophrenia.

Animals↗
PubMed1995

Taurine prevents haloperidol-induced changes in striatal neurochemistry and behavior.

Repeated daily administration of haloperidol produces changes in striatal neurochemistry (decreased dopamine synthesis, upregulation of D2 receptors) and behavior (increasing catalepsy). Coadministration of taurine greatly attenuated these neuroleptic-induced changes. Possible mechanisms of taurine's mitigating effects are its attenuating influences on glutamatergic transmission and its actions as a GABAA agonist. The possibility was discussed of adding taurine to chronic antipsychotic regimens to block the side-effects typically accompanying such therapy.

Animals↗
PubMed1995

Differential recovery of volitional motor function, lateralized cognitive function, dopamine agonist-induced rotation and dopaminergic parameters in monkeys made hemi-parkinsonian by intracarotid MPTP infusion.

There is still controversy regarding the frequency and extent of spontaneous functional recovery in primate models of parkinsonism, perhaps in part stemming from the variety of ways in which recovery has been assessed. The present study examined functional recovery in monkeys made unilaterally parkinsonian by intracarotid infusion of MPTP. Monkeys were evaluated prior to lesioning and for at least 1 year after lesioning on a battery of tests including a rating of spontaneous behaviors, a learned reaction time/movement time task, tests of lateralized neglect or inattention (i.e. lateralized reward retrieval task, extinction with double simultaneous stimulation, and response to a target moving from one hemispace to the other), and rotational asymmetry in response to a dopamine agonist. Some animals also received 6-[18F]Fluoro-L-Dopa (F-DOPA) position emission tomography (PET) scans before MPTP, when symptomatic, and when showing signs of functional recovery. These animals were sacrificed for post mortem neurochemical assessment following the last PET scan. Results showed that estimates of functional recovery in hemi-parkinsonian monkeys may depend upon the behavioral assay used. Even in behavioral tasks that were sensitive to recovery effects, the degree of functional recovery shown by an animal on one such task did not predict recovery on another. This may in part be due to the inherent difficulty in designing behavioral tests to assess basal ganglia functioning, when there is no consensus concerning which aspects of behavior the normal basal ganglia actually control.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1995

Reevaluation of the mesolimbic hypothesis of antipsychotic drug action.

Conventional neuroleptic drugs are thought to derive their antipsychotic efficacy through influences on the mesolimbic dopamine (DA) system. In contrast, motor side effects of these drugs are suggested to follow from influences on the nigrostriatal DA system. This conceptualization is based on the assumption that behaviors mediated by the mesolimbic DA system are involved in schizophrenia while behaviors controlled by the nigrostriatal system are not. In this article, it is argued that although assumptions about mesolimbic activities may indeed be correct, those concerning the nigrostriatal system certainly are not. This being the case, drugs with mesolimbic-specific activity may not have significant antipsychotic potency and probably will not be free of motor side effects. The current thrust of neuropharmacology, which emphasizes development of drugs with pharmacological specificity rather than anatomical selectivity, is more likely to generate new antipsychotic agents with a reduced risk of motor side effects.

Antipsychotic Agents↗
PubMed1994

Effects of experience on striatal sensory responses.

It has been well documented that striatal neurons encode and process sensory information. It was the aim of the present experiment to determine the extent to which behavioral experience influenced striatal sensory responses. Single units were recorded in the striatum of awake restrained cats as they were adapted to the recording situation. To facilitate recording, cats were rewarded with milk for remaining quiet and motionless. As animals evidenced familiarity with the testing environment, striatal neurons showed heightened sensory receptivity. These results indicate the important influence of behavioral determinants of striatal sensory responses. The nature of the behavioral experience may determine the way in which sensory information is processed in this part of the basal ganglia.

Animals↗
PubMed1993

Anti-glutamatergic effects of clozapine.

Clozapine (Cz) is unique in its efficacy with treatment refractory patients and its freedom from motor side effects. The present work shows that Cz, even after dopamine depletion, suppresses responses evoked via the monosynaptic glutamatergic corticostriatal pathway. In addition, Cz is effective in displacing [3H]MK-801 from striatal homogenates. These data indicate that Cz is a glutamate antagonist. It is unclear, however, if this pharmacological action could explain Cz's lack of motor effects and it's antipsychotic potency.

Animals↗
PubMed1993

Acute administration of haloperidol enhances dopaminergic transmission.

It has been demonstrated that haloperidol, by blocking presynaptic D2 receptors, enhances dopamine release. However, it is generally assumed that augmentation of dopaminergic transmission is precluded by haloperidol's postsynaptic actions. This assumption was assessed in the present experiment by testing the effects of acute haloperidol administration on the activity of the striatum. Somatosensory stimulation was used to evoke striatal field potentials in rats anesthetized with either urethane or sodium pentobarbital. Haloperidol suppressed striatal responses in a dose-dependent fashion. Enhanced dopaminergic activity, caused by i.v. cocaine or substantia nigra stimulation, similarly suppressed striatal responses. Rather than blocking the effects of cocaine in the striatum, coadministration of haloperidol was additive, causing increased suppression. Substantia nigra lesions that depleted striatal dopamine blocked the suppressive effects of haloperidol. Administration of R-(+)-8-chloro-2,3,4,5-tetrahydro-3- methyl-5-phenyl-1H-3-benzazepine-7-ol to prevent postsynaptic actions of dopamine mediated by D1 receptors did not attenuate haloperidol-induced suppression. The present data suggest that acute administration of haloperidol actually augments dopaminergic activity due to relatively strong presynaptic actions and relatively weak postsynaptic blocking effects. It is plausible that this initial increase in dopaminergic transmission may participate in producing the neural changes evoked by chronic haloperidol administration that allow this drug to have antipsychotic potency.

Animals↗