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Query: UMLS:C0751295 (memory loss)
 3,619 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

At the present time, it seems unlikely that progressive neurodegenerative diseases, such as ALS, Parkinson's disease, and dementia of the Alzheimer type, are triggered by environmental agents with excitotoxic potential. These include excitotoxic agents that behave as glutamate agonists or disrupt energy metabolism: both types elicit permanent but self-limiting neuronal diseases with patterns of neuronal deficit that reflect selective chemical exposure (MPP+ and parkinsonism), differential susceptibility to energy dysmetabolism (NPA and dystonia), or the distribution of glutamate-receptors (domoic acid and memory loss). If environmental agents play an etiologic role in progressive neurodegenerative diseases, they are likely to target a critical, irreplaceable neuronal molecule that is required to maintain long-term neuronal integrity.
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PMID:Are human neurodegenerative disorders linked to environmental chemicals with excitotoxic properties? 132 79

The overstimulation of receptors for L-glutamate, particularly those of the N-methyl-D-aspartate (NMDA) type, has been suggested to play a role in mediating damage in a variety of neurodegenerative conditions or disorders ranging from ischemia/hypoxia to senile dementia of the Alzheimer's type (SDAT). We report here that the functional deficits and histological damage mediated by the overactivation of NMDA receptors in the Fischer 344 rat hippocampus can be blocked effectively by systemic administration of the noncompetitive NMDA antagonist, MK-801. These results suggest that MK-801 may be effective clinically in attenuating memory loss and hippocampal damage in disorders associated with the overstimulation of NMDA receptors.
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PMID:MK-801 prevents cognitive and behavioral deficits produced by NMDA receptor overstimulation in the rat hippocampus. 254 91

Excitatory amino acids (EAA) such as glutamate and aspartate are major transmitters of the cerebral cortex and hippocampus, and EAA mechanisms appear to play a role in learning and memory. Anatomical and biochemical evidence suggests that there is both pre- and postsynaptic disruption of EAA pathways in Alzheimer's disease. Dysfunction of EAA pathways could play a role in the clinical manifestations of Alzheimer's disease, such as memory loss and signs of cortical disconnection. Furthermore, EAA might be involved in the pathogenesis of Alzheimer's disease, by virtue of their neurotoxic (excitotoxic) properties. Circumstantial evidence raises the possibility that the EAA system may partially determine the distribution of pathology in Alzheimer's disease and may be important in producing the neurofibrillary tangles, RNA reductions and dendritic changes which characterize this devastating disorder. In this article, we will review the evidence suggesting a role for EAA in the clinical manifestations and pathogenesis of Alzheimer's disease.
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PMID:Excitatory amino acids and Alzheimer's disease. 255 68

Domoic acid (DOM), 1 to 50 microM, a glutamate agonist responsible for several neurological effects such as loss of memory and confusion, induced the death of cultured neurons of chick embryonic retina, in a concentration- and Ca(2+)-dependent manner. This effect was blocked by 100 microM CNQX, a competitive antagonist of the non-NMDA receptor, but not by 10 microM MK-801, a non-competitive antagonist of the NMDA receptor. DOM also induced inositol triphosphate (ip3) accumulation 4 to 7 times above basal levels. This effect was also dependent on external Ca2+ and was entirely blocked by 100 microM CNQX, but not by 10 microM MK-801. These results suggest that DOM interaction with non-NMDA glutamate receptors mediates signal transduction with ip3 accumulation and cell death.
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PMID:Domoic acid induces neurotoxicity and ip3 mobilization in cultured cells of embryonic chick retina. 758 Oct 17

Brief perfusion of salines containing elevated (10.5-50 mM) [K+] plus glutamate (2.5 or 5 mM) could erase long-term potentiation (LTP) in rat hippocampal slices. Prolonged perfusion with high-[K+]/glutamate could cause persistent neuronal depression lasting > 1 h. LTP erasure occurred in the absence of generalized depression of axonal responsiveness, while persistent neuronal depression was associated with a failure of antidromic invasion of cells. The protocols used may contribute to the development of a model for the cellular study of memory loss following neurological dysfunction.
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PMID:Perfusion with high potassium plus glutamate can cause LTP erasure or persistent loss of neuronal responsiveness in the CA1 region of the hippocampal slice. 809 26

Monosodium glutamate (4.0 mM) administered immediately after a visual reminder presented to day-old chickens between 7.5 min and 24 h following a single trial passive avoidance learning task produced transient losses of memory on retention test, an effect not observed in the absence of a reminder or when the reminder was given 48 h post-learning. The duration of the transient deficit decreased with increasing interval between the training and the reminder trial. The time of onset of memory loss after the reminder trial appeared to increase with increasing interval between the training and the reminder trials. The results suggest that, for a period of at least up to 24 h after passive avoidance training, retrieval of memory may lead to processes which are sensitive to inhibition by glutamate, with the duration of sensitivity post-retrieval decreasing as the period of memory consolidation increases. The results extend previously reported findings with rodents and suggest the possibility that consolidation of a stable memorial representation of a learning experience may take place over several days and may entail the concurrent laying down of a stable retrieval mechanism.
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PMID:Administration of glutamate following a reminder induces transient memory loss in day-old chicks. 871 16

Lanthanum chloride (5.0 mM) administered immediately after a visual reminder presented to day-old chickens between 7.5 min and 48 h following a single trial passive avoidance learning task produced an immediate but transient loss of memory on retention test, an effect not observed in the absence of a reminder. The duration of the transient deficit was relatively stable with lanthanum chloride consistently inducing a loss of memory that was evident 5 min after the reminder, with recovery by 10-15 min. The results suggest that, for a period of at least up to 48 h after passive avoidance training, the activation of memory retrieval by a reminder stimulus may lead to processes which are sensitive to inhibition by the calcium channel antagonist lanthanum chloride. These results extend previously reported findings implicating the involvement of glutamate-sensitive channels in a transient memory process that is also activated as a result of a reminder stimulus, but that is no longer present 48 h after training. The glutamate-sensitive mechanism appears to be a secondary mechanism activated following memory retrieval and to be dependent on the level of memory consolidation that the memory for the original experience has undergone. The results presented here suggest that lanthanum chloride, a calcium channel antagonist, inhibits memory retrieval in the day-old chick. This effect implicates calcium channel mediated processes in immediate memory recall. Further, the results suggest the lanthanum inhibits a primary mechanism, that precedes that glutamate-sensitive mechanism identified previously and that both are dependent on the activation of memory retrieval by a reminder.
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PMID:Administration of lanthanum chloride following a reminder induces a transient loss of memory retrieval in day-old chicks. 888 24

Glutamate is the most widespread excitatory transmitter in the CNS and is probably involved in LTP, a neural phenomenon which may be associated with learning and memory formation. Intracerebral injection of large amounts of glutamate between 5 min and 2.5 min after passive avoidance learning in young chicks inhibits short-term memory, which occurs between 0 and 10 min post-learning in a three-stage model of memory formation first established by Gibbs and Ng(25) [Physiol. Behav. 23:369-375; 1979]. This effect may be attributed to non-specific excitation. Blockade of glutamate uptake by L-aspartic and beta-hydroxamate also abolishes this stage of memory, provided the drug is administered within 2.5 min of learning. Interference with either production of percursors for transmitter glutamate in astrocytes or with glutamate receptors is also detrimental to memory formation, but the effects appear much later. After its release from glutamatergic neurons, glutamate is, to a large extent, accumulated into astrocytes where it is converted to glutamine, which can be returned to glutamatergic neurons and reutilized for synthesis of transmitter glutamate, and partly oxidized as a metabolic substrate. The latter process leads to a net loss of transmitter glutamate which can be compensated for by de novo synthesis of a glutamate precursor alpha-ketoglutarate (alpha KG) in astrocytes, a process which is inhibited by the astrocyte-specific toxin fluoroacetate (R. A. Swanson, personal communication). Intracerebral injection of this toxin abolishes memory during an intermediate stage of memory processing occurring between 20 and 30 min post-training (50) [Cog. Brain Res, 2:93-102; 1994]. Injection of methionine sulfoximine (MSO), a specific inhibitor of glutamine synthetase, which interferes with the re-supply of transmitter glutamate to neurons by inhibition of glutamine synthesis in astrocytes, has a similar effect. This effect of MSO is prevented by intracerebral injection of glutamate, glutamine, or a combination and alpha KG and alanine. MSO must be administered before learning, but does not interfere with acquisition since short-term memory remains intact. Administration of either the NMDA antagonist AP5, the AMPA antagonist DNQX, or the metabotropic receptor antagonist MCPF, also induces amnesia. Memory loss in each case does not occur until after 70 min post-training, during a protein synthesis-dependent long-term memory stage which begins at 60 min following learning. However, to be effective, AP5 must be administered within 60 s following learning, MCPG before 15 min post-learning, and DNQX between 15 and 25 min after learning. Together, these findings suggest that learning results in an immediate release of glutamate, followed by a secondary release of this transmitter at later stages of processing of the memory trace, and that one or both of these increases in extracellular glutamate concentration are essential for the consolidation of long-term memory. Since both fluoroacetate and MSO act exclusively on glial cells, the findings also show that neuronal-glial interactions are necessary during the establishment of memory.
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PMID:Complex roles of glutamate in the Gibbs-Ng model of one-trial aversive learning in the new-born chick. 899 8

Changes in brain extracellular space (ECS) volume, composition, and geometry are a consequence of neuronal activity, of glial K+, pH, and amino acid homeostasis, and of changes in glial cell morphology, proliferation, and function. They occur as a result of repetitive neuronal activity, seizures, anoxia, injury, inflammation, and many other pathological states in the CNS, and may significantly affect signal transmission in the CNS. Activity-related or CNS damage-related cellular swelling is compensated for by ECS volume shrinkage and, as a consequence, by a decrease in the apparent diffusion coefficients (ADCs) of neuroactive substances diffusing in the ECS. Changes in cellular morphology, such as occur during aging, could also result in changes of ECS volume and geometry. We provide evidence for limited diffusion in rat cortex, corpus callosum, and hippocampus in the aging brain that correlates with changes in glial volume and the extracellular matrix. In all structures, the mean ECS volume fraction alpha (alpha = ECS volume/total tissue volume) and nonspecific uptake k' are significantly lower in aged rats (26-32 months old) than in young adult brain. Compared to young adult brain, in the aged brain we found an increase in GFAP staining and hypertrophied astrocytes with thicker processes which, in the hippocampus, lost their radial organization. The tortuosity (lambda = square root of D/ADC) was lower in the cortex and CA3 region. Immunohistochemical staining for fibronectin and chondroitin sulfate proteoglycans revealed a substantial decrease that could account for a decrease in diffusion barriers. Diffusion parameters alpha, lambda, and k' in the aging brain after cardiac arrest changed substantially faster than in the young adult brain, although the final values were not significantly different. This suggests that the smaller extracellular space during aging results in a greater susceptibility of the aging brain to anoxia/ischemia, apparently due to a faster extracellular acidosis and accumulation of K+ and toxic substances, for example, glutamate. We conclude that during aging the movement of substances is more hindered in the narrower clefts. This is partly compensated for by a decrease in the diffusion barriers that may be formed by macromolecules of the extracellular matrix. Diffusion parameters can affect the efficacy of synaptic as well as extrasynaptic transmission by a greater accumulation of substances, because they diffuse away from a source more slowly, or induce damage to nerve cells if these substances reach toxic concentrations. Diffusion parameters are also of importance in the "crosstalk" between synapses, which has been hypothesized to be of importance during LTP and LTD. We can, therefore, assume that the observed changes in ECS diffusion parameters during aging can contribute to functional deficits and memory loss.
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PMID:Diffusion constraints and neuron-glia interaction during aging. 995 27

Many neuropsychiatric disorders affect memory. Brain regions important in the neuroanatomic substrate of memory include the hippocampus, and sections of the frontal, temporal, and parietal cortices and the thalamus. Acetylcholine and many other neurotransmitters and neuromodulators including dopamine, glutamate, GABA, the catecholamines, and estrogen modulate cognitive function. Treatment approaches to memory loss typically use Alzheimer's dementia as the template, and are discussed in this report.
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PMID:Approaches to memory loss in neuropsychiatric disorders. 1129 Oct 22


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