Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0751295 (memory loss)
 3,619 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present experiment examined whether previous experience with a drug would decrease the potential of the drug to produce state dependent retention (SDR) for a passive avoidance response in rats. In the first experiment, a single injection of sodium pentobarbital (20 mg/kg) given on six consecutive days before the training day slightly reduced, but did not block, pentobarbital-induced SDR. In Experiment Two, four preexposure injections of 5 IU/kg insulin reduced the magnitude of memory loss produced by administration of the hormone prior to training. As with pentobarbital, however, preexposure to insulin did not completely block the amnestic effect of the hormone. A subsequent experiment demonstrated that the decrease in the strength of insulin-induced SDR in insulin preexposed rats was not the result of enhanced acquisition. Collectively, these data indicate that noncontingent preexposure to an amnestic treatment may decrease the magnitude of memory loss that would normally result from the administration of that treatment during training.
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PMID:The effects of preexposure to the drug on state dependent retention. 174 81

Mexiletine is a Class IB antiarrhythmic which has basic and clinical electrophysiologic properties similar to lidocaine. Like other Class I antiarrhythmic agents, mexiletine blocks the rapid inward sodium current responsible for phase 0 of the action potential. It has been noted in the clinical electrophysiology laboratory to have minimal effect on sinus node function and AV nodal and His-Purkinje system conduction. Pharmacokinetic studies have shown that oral absorption is rapid with bioavailability of 80-90%. Mexiletine is predominantly metabolized by the liver with elimination half-life of 9 to 12 hours. The antiarrhythmic effects of the primary drug's metabolites remain to be defined. Hemodynamic studies have shown mexiletine to have a lesser negative inotropic effect than procainamide or disopyramide. Although mexiletine as a single agent successfully suppresses 60 to 80% of spontaneous ventricular arrhythmias, it has lower efficacy in suppression of induced ventricular arrhythmias. Multiple studies have shown that as monotherapy mexiletine is effective in preventing the induction of ventricular tachycardia in approximately 20% of patients. When used in combination with a Class IA antiarrhythmic drug for suppression of induced ventricular arrhythmias, multiple investigators have reported greater efficacy. Neurological side effects (tremor, dizziness, memory loss) occur in approximately 10% of patients while gastrointestinal side effects (nausea, anorexia, gastric irritation) occur in up to 40% of patients. Proarrhythmia or other serious toxicity from the drug is uncommon.
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PMID:Mexiletine: pharmacology and therapeutic use. 218 14

Human amnesia cases (after surgical removal of the hippocampi or brain anoxia) have clearly established the critical role of the hippocampal formation in anterograde amnesia. Other parts of the brain may also contribute to anterograde amnesia (mammillary bodies, medial thalamus). In neurodegenerative diseases (and specially in Alzheimer's disease) amnesia is often the prominent symptom, but the brain lesions are not restricted to the hippocampal formation. In Alzheimer's disease they involve also the cerebral cortex and several subcortical nuclei. Physiological brain aging is also associated with some degree of memory impairment, but much less severe than in Alzheimer's disease. The issue of the nature and the mechanisms of the memory impairment associated with age and with Alzheimer's disease is very important, because the frequency of these problems increases dramatically as the populations of the world is growing older. There is some evidence that neuronal loss and alterations in neurotransmitter systems occur in the aged subject, but the relationship between such changes and the age-related memory deficit is far from being clear. In Alzheimer's disease, the loss of memory is likely to be due to neuronal loss in cerebral cortex and hippocampal formation, along with alterations in neurotransmitter systems (specially cholinergic, monoaminergic and aminoacidergic systems). The work in experimental animals has largely confirmed the critical role of the hippocampal formation, as well as identified other critical structures. The mechanisms of the age-related memory impairment can be to some extent investigated in aged animals. In the aged rat there is evidence that several neurotransmitter networks are altered. Alteration in the dopaminergic and cholinergic systems have been extensively studied, but the involvement of other systems is likely. Learning and memory deficits are consistently observed in a sub-population of aged rodents (as well as in other species including non-human primates). For instance some aged rats do have a deficit in the performance of a spatial learning task such as the "water maze". There is some evidence that this deficit is due, at least in part, to alterations in the functions of the hippocampal formation. In other words, if aged rats have a spatial memory deficit, it might be due to changes in hippocampal neuronal circuitry. The study of age-related alterations in hippocampal neuronal networks, using electrophysiological techniques have shown that several neuronal properties such as resting membrane potential, membrane resistance or sodium spike amplitude are not altered in the aged rat hippocampus.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Aging of memory mechanisms]. 778 Jul 90

Adipsia and hypernatremia is a syndrome which can be observed among children and adults with various congenital or acquired diseases of the brain. We can include the primary neoplasms and the metastatic among the causes of this syndrome. We display the case of a 63-year-old man who presented time-space disorientation, loss of memory fixation, visual hallucinations, unstable walking and absence of the voluntary ingestion of liquids. The serum electrolytes showed serum sodium concentration of 188 mEq/l with plasma osmolality above 380 mOs/kg. Both the forced water intake and the intravenous rehydration restored the plasma osmolality and the normal levels of serum sodium. The magnetic resonance (MR) neurohypophyseal area showed a neoformative lesion at the middle line which affected septum ventricular and hypothalamic area. We analyse the pathophysiologic mechanisms, the clinical and laboratory data, as well as the therapeutic and the evolution of the cases which have been published in the literature.
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PMID:[Adipsia and hypernatremia as the first manifestation of hypothalamic astrocytoma. Report of a case and review of the literature]. 1098 33

Domoic acid is a shellfish toxin which produces neurodegeneration and CNS dysfunction, notably a loss of short-term memory. This toxin was found in blue mussels (Mytilus edulis) cultivated in river water in the east coast of Prince Edward Island in Canada and caused human poisoning. The toxin was localized in the stomach of blue mussels, which was engorged with algae, Nitzschia pungens, that were filtered from the surrounding water. The toxin was isolated from contaminated mussels or phytoplankton, and identified chemically as domoic acid (DOM) which is a tricarboxylic amino acid. Due to its structural resemblance to glutamic, aspartic and kainic acids, DOM was considered to produce excitotoxicity by similar mechanism(s). However, the latest evidence indicates differences in its mode of action from these excitatory agonists. We propose that DOM induces toxicity via changes in intracellular concentration of Ca2+ ([Ca2+]i). Results of our studies demonstrate that DOM elevated [Ca2+]i in brain slices. Glucose deprivation and removal of Na+ from the Krebs-bicarbonate medium further elevated [Ca2+]i, suggesting a relationship between glucose metabolism (cell energy), Na+ and Ca2+ transfer across neuronal membrane. DOM-induced rise in [Ca2+]i was due to enhanced Ca2+ influx and its mobilization from the endoplasmic reticulum. In addition, diminished Ca2+-ATPase activity due to lack of ATP, and variable amounts and expression of calcium binding proteins (CaBP) appear to contribute to an elevation in [Ca2+]i in response to DOM. Most interestingly, DOM inhibited Ca2+ and calmodulin-stimulated adenylate cyclase activity in brain membranes, resulting in reduced level of cyclic AMP. Cyclic AMP is known to activate protein kinase A to enhance phosphorylation of Ca2+ channels, thereby, reducing Ca2+ influx to prevent the development of Ca2+ overload which is detrimental to neuronal cell function (neuroprotection). However, DOM reduced cyclic AMP level, diminishing the feedback control of cyclic AMP on Ca2+ influx via Ca2+ channels, thereby, allowing continuing enhanced Ca2+ influx, resulting in Ca2+ overload which adversely affects many intracellular processes to induce toxicity. Ca2+ and CaM-stimulated adenylate cyclase activity in brain is highly correlated with the acquisition and retention of memory in different organisms. Calcium binding proteins bind Ca2+ reversibly and provide intracellular Ca2+ buffering, thereby, protecting neuronal cell from damage by Ca2+ overload in response to DOM. DOM appears to interfere with the cross talk between Ca2+ and cyclic AMP which is necessary for neuronal cell function. We have also demonstrated that DOM stimulates GLU release from synaptosomes and may produce some of its toxic effects via excess GLU in the neuronal synapse. In conclusion, DOM-induced neurodegeneration resulting in a loss of memory is mediated by Ca2+ overload, inhibition of Ca2+ and CaM-stimulated adenylate cyclase activity, and/or by the enhanced GLU release in rat brain.
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PMID:Domoic acid-induced neurodegeneration resulting in memory loss is mediated by Ca2+ overload and inhibition of Ca2+ + calmodulin-stimulated adenylate cyclase in rat brain (review). 1099 28

Hypodipsic hypernatremia (HH) represents a pathological increase in serum sodium due to a lack of thirst and defect in hypothalamic osmoreceptors. While 15% of patients with HH have a vascular aetiology, few cases have been described. Moreover, the presence of such abnormalities in the amnestic patient can have particularly threatening implications, as HH tends to recur unless the patient complies with a regimen of water intake. This study reports the case of a 46-year-old male admitted for rehabilitation of functional deficits following subarachnoid haemorrhage (SAH), with clipping of an anterior communicating artery (ACoA) aneurysm. Clinical examination was remarkable for profound short-term memory loss and inability to retain new information. Blood chemistry on admission showed a serum sodium level of 160 mEq/L, increasing to 167 mEq/L the following day. The patient denied thirst, and showed no clinical signs of dehydration. Neuroendocrine evaluation revealed diabetes insipidus (DI) and HH. Treatment initially included DDAVP and intravenous hydration, later supplemented with chlorpropramide. Stabilization of serum sodium and osmolality did not ensue until the treatment regimen included hydrochlorothiazide and supervision of enforced fluid intake. Endocrine abnormalities may be encountered among patients with vascular lesions adjacent to the hypothalamus. Rehabilitation interventions include establishing a structured medication regimen with fluid administration in the amnestic patient with hypothalamic dysfunction.
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PMID:Hypodipsic hypernatremia and diabetes insipidus following anterior communicating artery aneurysm clipping: diagnostic and therapeutic challenges in the amnestic rehabilitation patient. 1168 95

The cytosolic posttranslational protein-modifying mechanism of monoADP-ribosylation has been implicated in long-term potentiation, a synaptic model of memory formation. The current study investigated the effect of inhibiting mono(ADP-ribosyl) transferase on memory for the passive avoidance task in day-old chicks (white Leghorn-black Australorp). Various doses of novobiocin or menadione sodium bisulfite were administered intracranially at different times before or after training. Control chicks were administered saline at matched times. Novobiocin (650 microM) or menadione sodium bisulfite (250 microM) administered between 5.0 min pretraining and 2.5 min posttraining was found to cause a persistent loss of retention from 120 min posttraining. These data provide the first demonstration that monoADP-ribosylation is required for the maintenance of long-term memory. Furthermore, the temporal characteristics of the memory loss caused by monoADP-ribosylation inhibition appears to exclude this mechanism as a downstream effect of the well-established nitric oxide activity previously shown to occur within 40 min of passive avoidance training.
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PMID:Inhibition of monoADP-ribosylation prevents long-term memory consolidation of a single-trial passive avoidance task in the day-old chick. 1207 76

Lead has an obvious potential to disturb learning ability, adaptive responses, and other aspects of behavior and even personality in those who may appear healthy according to conventional medical criteria. These disturbances are shown to be associated with alterations in ionic, cholinergic, and dopaminergic neurotransmission in the central nervous system (CNS). The present experiment was designed to study the neurotoxic consequences of lead exposure on neurotransmitters like dopamine, serotonin, norepinephrine, and activity of acetylcholinestrase, as well as some ions like zinc, calcium, sodium, and potassium. The locomotory functions along with cognitive functions and memory loss were also studied at various dose levels. Lead was administrated orally in doses of 10 mg/kg, 50 mg/kg, and 200 mg/kg for a period of 12 wk and the study was done at the end of exposure. A dose-dependent decrease in the concentration of sodium, potassium, and zinc was observed; there was increase in the concentrations of lead and calcium. The most significant change noted was the decrease in activity of the acetylcholinestrase and other neurotransmitters. Lead exposure affected the locomotor and cognitive functions. Short-term memory remained unchanged at all lead exposure doses.
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PMID:Relationship between lead-induced biochemical and behavioral changes with trace element concentrations in rat brain. 1279 76

Patients presenting with subacute amnesia are frequently seen in acute neurological practice. Amongst the differential diagnoses, herpes simplex encephalitis, Korsakoff's syndrome and limbic encephalitis should be considered. Limbic encephalitis is typically a paraneoplastic syndrome with a poor prognosis; thus, identifying those patients with potentially reversible symptoms is important. Voltage-gated potassium channel antibodies (VGKC-Ab) have recently been reported in three cases of reversible limbic encephalitis. Here we review the clinical, immunological and neuropsychological features of 10 patients (nine male, one female; age range 44-79 years), eight of whom were identified in two centres over a period of 15 months. The patients presented with 1-52 week histories of memory loss, confusion and seizures. Low plasma sodium concentrations, initially resistant to treatment, were present in eight out of 10. Brain MRI at onset showed signal change in the medial temporal lobes in eight out of 10 cases. Paraneoplastic antibodies were negative, but VGKC-Ab ranged from 450 to 5128 pM (neurological and healthy controls <100 pM). CSF oligoclonal bands were found in only one, but bands matched with those in the serum were found in six other patients. VGKC-Abs in the CSF, tested in five individuals, varied between <1 and 10% of serum values. Only one patient had neuromyotonia, which was excluded by electromyography in seven of the others. Formal neuropsychology testing showed severe and global impairment of memory, with sparing of general intellect in all but two patients, and of nominal functions in all but one. Variable regimes of steroids, plasma exchange and intravenous immunoglobulin were associated with variable falls in serum VGKC-Abs, to values between 2 and 88% of the initial values, together with marked improvement of neuropsychological functioning in six patients, slight improvement in three and none in one. The improvement in neuropsychological functioning in seven patients correlated broadly with the fall in antibodies. However, varying degrees of cerebral atrophy and residual cognitive impairment were common. Over the same period, only one paraneoplastic case of limbic encephalitis was identified between the two main centres. Thus, VGKC-Ab-associated encephalopathy is a relatively common form of autoimmune, non-paraneoplastic, potentially treatable encephalitis that can be diagnosed by a serological test. Establishing the frequency of this new syndrome, the full range of clinical presentations and means of early recognition, and optimal immunotherapy, should now be the aim.
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PMID:Potassium channel antibody-associated encephalopathy: a potentially immunotherapy-responsive form of limbic encephalitis. 1496 Apr 97

Juhn Wada developed a test while in Montreal designed to definitively confirm hemispheric lateralization of speech in candidates for surgical treatment of epilepsy. By unilateral intra-carotid administration of a bolus of a general anesthetic, classically sodium amobarbital, function can be tested in the non-injected hemisphere, while the injected side is dysfunctional. The test has been expanded to test memory functions in the hemisphere (temporal lobe) contralateral to expected surgery (memory reserve) in the hope of contra-indicating surgery that may result in global amnestic syndromes (patient HM). Conversely, risk of material-specific memory loss following surgery can be assessed by testing memory in the hemisphere/temporal lobe to be operated ("functional adequacy"). Memory dysfunction, when concordant with EEG seizure onset and chosen side of temporal lobe surgery has also been shown to correlate with favourable post-operative seizure outcome. Nevertheless, the test remains invasive, requiring an angiogramme. Non-invasive alternatives such as fMRI and PET and their reported reliability compared to a Wada test are discussed. A world-wide shortage of amobarbital has led to the use of some other anesthetic agents. Overall, the indications for the test and the manner in which it is performed vary greatly from one institution to the next. It is used almost systematically in some institutions and very rarely in others. Future perspectives are discussed.
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PMID:[What is the current role of a Wada test in the pre-surgical work-up of pharmacologically intractable epilepsy in adults?]. 1533 62


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