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

To investigate experimentally the mnemonic and neuropathological effects of blockage of the posterior cerebral arteries (PCA), a cerebrovascular accident that can lead to global anterograde amnesia in humans, we permanently occluded these arteries bilaterally in six monkeys and then evaluated their performance on a visual recognition task, after which we assessed the extent of their ischemic infarcts. The latter showed substantial individual variation, ranging from almost no damage in one case to massive unilateral injury of both the ventromedial o occipitotemporal cortex and hippocampal formation in another. In the four remaining cases, however, the infarcts fell within a narrow range, being confined almost entirely to the hippocampal formation and parahippocampal gyrus, and then only to restricted portions of these structures, unilaterally in one case, and bilaterally in the three others. Performance on the recognition task was related to the presence and bilaterality of the hippocampal injury. Thus, the case without any hippocampal damage performed at a rate equal to that of normal controls; the case with unilateral hippocampal damage was mildly impaired; and the three cases with bilateral infarctions, involving between 20 and 55% of the hippocampal formation, showed substantial impairment, with scores averaging 20% below those of normal controls. The only subfields of the hippocampus damaged in common in these cases were CA1 and CA2. Paradoxically, the memory loss found in these three animals with only partial bilateral hippocampal damage was significantly greater than that found in animals with total bilateral ablation of the hippocampal formation, whose scores averaged only 10% below those of normal controls. Possible explanations for this extremely puzzling outcome are proposed.
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PMID:Mnemonic and neuropathological effects of occluding the posterior cerebral artery in Macaca mulatta. 271 Mar 18

The CA1 and hilar fields of the hippocampus are highly vulnerable to lack of oxygen after interruption of blood flow to the brain. Severe anterograde memory loss, seen in a significant proportion of heart attack survivors, has been attributed to selective bilateral ischaemic damage to the hippocampus. Animal models of global ischaemia, induced by extracranial occlusion of the major ascending arteries, enable assessment of the neuropathological and functional consequences of transient interruption of cerebral blood flow, and can inform strategies to reduce or alleviate ischaemic brain damage. This review focuses firstly on the nature of cognitive deficits induced by global ischaemia, how far they are consistent with lesion-based accounts of hippocampal function, and the extent to which these deficits can be correlated with CA1 cell loss. The second focus of the review is to examine the limited evidence for graft-induced recovery of cognitive function in animals subjected to global ischaemia. Recent findings that grafted foetal cells from discrete hippocampal fields follow appropriate laminar routes to form functional connections with host neurons, and that growth factors protect cells from ischaemic damage, have suggested that CA1 or trophic grafts placed in the region of ischaemic CA1 cell loss might restore or protect this vulnerable sector, and reduce cognitive deficits.
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PMID:Cognitive deficits induced by global cerebral ischaemia: relationship to brain damage and reversal by transplants. 788 Apr 47

Long-term memory is thought to be subserved by functional remodeling of neuronal circuits. Changes in the weights of existing synapses in networks might depend on voltage-gated potassium currents. We therefore studied the physiological role of potassium channels in memory, concentrating on the Shaker-like Kv1.1, a late rectifying potassium channel that is highly localized within dendrites of hippocampal CA3 pyramidal and dentate gyrus granular cells. Repeated intracerebroventricular injection of antisense oligodeoxyribonucleotide to Kv1.1 reduces expression of its particular intracellular mRNA target, decreases late rectifying K+ current(s) in dentate granule cells, and impairs memory but not other motor or sensory behaviors, in two different learning paradigms, mouse passive avoidance and rat spatial memory. The latter, hippocampal-dependent memory loss occurred in the absence of long-term potentiation changes recorded both from the dentate gyrus or CA1. The specificity of the reversible antisense targeting of mRNA in adult animal brains may avoid irreversible developmental and genetic background effects that accompany transgenic "knockouts".
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PMID:Reversible antisense inhibition of Shaker-like Kv1.1 potassium channel expression impairs associative memory in mouse and rat. 911 6

High alcohol consumption for long periods of time causes significant hippocampal neurodegeneration in rodents. A single study using neuronal density measures has reported similar findings in humans. The present study aims to substantiate these findings in human alcoholics using unbiased stereological techniques. Both amnesic (n = 5) and nonamnesic (n = 7) chronic alcoholics were selected and compared with nonalcoholic controls (n = 8) and patients with marked memory loss and hippocampal neurodegeneration caused by Alzheimer's disease (n = 4). Hippocampal volume was significantly reduced in the alcoholics and in patients with Alzheimer's disease. However, in alcoholics the volume reduction occurred exclusively in the white matter, whereas both the gray and white matter were reduced in the patients with Alzheimer's disease. Neuron loss occurred exclusively from the CA1 and subiculum subregions of the hippocampus in Alzheimer's disease. No neuron loss occurred from any subregion of the hippocampus in alcoholics. There were no correlations with age and any of the volume or neuron number measures. Hippocampal volume correlated with brain volume and with the regional gray and white matter volumes within the hippocampus. In addition, hippocampal gray matter volume correlated with the number of CA1 pyramidal neurons. These results do not support the theory that chronic alcohol consumption is neurotoxic to hippocampal pyramidal neurons in humans. Further, the present results suggest that changes observed in rodent models of alcoholism do not parallel those observed in humans, questioning the validity of such models.
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PMID:Chronic alcohol consumption does not cause hippocampal neuron loss in humans. 913 71

Evidence suggests that cholinergic input to the hippocampus plays an important role in learning and memory and that degeneration of cholinergic terminals in the hippocampus may contribute to the memory loss associated with Alzheimer's disease. One of the more prominent effects of cholinergic agonists on hippocampal physiology is the potentiation of N-methyl-D-aspartate (NMDA)-receptor currents by muscarinic agonists. Here, we employ traditional pharmacological reagents as well as m1-toxin, an m1 antagonist with unprecedented selectivity, to demonstrate that this potentiation of NMDA-receptor currents in hippocampal CA1 pyramidal cells is mediated by the genetically defined m1 muscarinic receptor. Furthermore, we demonstrate the colocalization of the m1 muscarinic receptor and the NR1a NMDA receptor subunit at the electron microscopic level, indicating a spatial relationship that would allow for physiological interactions between these two receptors. This work demonstrates that the m1-muscarinic receptor gene product modulates excitatory synaptic transmission, and it has important implications in the study of learning and memory as well as the design of drugs to treat neurodegenerative diseases such as Alzheimer's.
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PMID:Activation of the genetically defined m1 muscarinic receptor potentiates N-methyl-D-aspartate (NMDA) receptor currents in hippocampal pyramidal cells. 973 60

Although it is generally believed that amyloid beta (Abeta) peptides contribute to the pathogenesis of Alzheimer's disease, the precise role of these peptides in the development of memory loss of Alzheimer's disease, has not been fully understood. The present study examined the effect of several synthetic Abeta peptides on long-term potentiation (LTP), a cellular model of learning and memory, in rat hippocampal slices. Brief perfusion of slices with low concentrations (200 nM or 1 microM) of Abeta(1-42), Abeta(1-40) or their active fragment Abeta(25--35) significantly inhibited LTP induction without affecting the basal synaptic transmission and posttetanic potentiation in the dentate medial perforant path. A similar effect of Abeta(25-35) was also observed in the Schaffer collateral-CA1 pathway. When comparing actions of several Abeta variants derived from Abeta(25-35), the N-terminal sequence of Abeta(25-35) was found necessary for inhibiting LTP. In addition, Abeta variants lacking neurotoxic action and aggregating property were also able to block LTP, suggesting that this effect was neurotoxicity independent. Our findings demonstrated that subneurotoxic concentrations of Abeta peptides could strongly suppress long-term synaptic plasticity in the hippocampus. Such an effect might underlie the memory deficits seen in Alzheimer's disease before neuronal cell loss.
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PMID:Impairment of hippocampal long-term potentiation by Alzheimer amyloid beta-peptides. 1072 69

Memory loss in humans begins early in adult life and progresses thereafter. It is not known whether these losses reflect the failure of cellular processes that encode memory or disturbances in events that retrieve it. Here, we report that impairments in hippocampal long-term potentiation (LTP), a form of synaptic plasticity associated with memory, are present by middle age in rats but only in select portions of pyramidal cell dendritic trees. Specifically, LTP induced with theta-burst stimulation in basal dendrites of hippocampal field CA1 decayed rapidly in slices prepared from 7- to 10-month-old rats but not in slices from young adults. There were no evident age-related differences in LTP in the apical dendrites. Both the adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine and a positive AMPA receptor modulator (ampakine) offset age-related LTP deficits. Adenosine produced greater depression of synaptic responses in middle-aged versus young adult slices and in basal versus apical dendrites. These results were not associated with variations in A1 receptor densities and may instead reflect regional and age-related differences in adenosine clearance. Pertinent to this, brief applications of A1 receptor antagonists immediately after theta stimulation fully restored LTP in middle-aged rats. We hypothesize that the build-up of extracellular adenosine during theta activity persists into the postinduction period in the basal dendrites of middle-aged slices and thereby activates the A1 receptor-dependent LTP reversal effect. Regardless of the underlying mechanism, the present results provide a candidate explanation for memory losses during normal aging and indicate that, with regard to plasticity, different segments of pyramidal neurons age at different rates.
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PMID:Long-term potentiation is impaired in middle-aged rats: regional specificity and reversal by adenosine receptor antagonists. 1597 84

beta-Amyloid peptide (Abeta) is known to be involved in Alzheimer's disease (AD). Although the fibril form of Abeta is known to have neurotoxicity, it has been shown that not only the fibril form but also the oligomer form of Abeta may be related to the neuropathophysiology of AD, specifically to memory loss. Some studies have demonstrated that low concentrations of the Abeta oligomer impair long-term potentiation (LTP), a cellular model for learning and memory, after short exposure times in vivo and in vitro, although little is known about the mechanism involved in Abeta-mediated inhibition of LTP. In this study, we used the patch clamp whole-cell technique in rat hippocampal CA1 pyramidal neurons to study more precisely how the Abeta oligomer affects synaptic plasticity. The brief perfusion of slices with a low concentration (1microM) of Abeta(1-42) significantly impaired LTP induction of the excitatory input. The same concentration of Abeta did not affect basal transmission or paired-pulse facilitation. We also demonstrated that neither NMDAR-EPSCs nor the voltage-depended calcium channel (VDCC) currents were affected by the same concentration of Abeta(1-42) as used in the LTP experiments. These data suggest that Abeta mediated impairment of LTP induction is independent of NMDARs or VDCCs.
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PMID:Mechanism of impairment of long-term potentiation by amyloid beta is independent of NMDA receptors or voltage-dependent calcium channels in hippocampal CA1 pyramidal neurons. 1615 66

Subject KN has a persistent anterograde amnesia as a result of brain injury following meningitis in 1993. MRI scans reveal a bilateral decrease in the volume of his hippocampal region (dentate gyrus, CA1-4, subicular cortices) of approximately 45% in both the right and left hemispheres, although the volume of his perirhinal cortex appears normal. Aside from some changes to his occipital lobe and bilateral shrinkage of the amygdala, the rest of his brain appears normal on recent quantitative MRI scans. A striking feature of his memory loss is his ability to perform at normal levels on some tests of recognition, despite his consistent deficit on tests of recall. Two tests designed specifically to distinguish performance of two putative divisions of recognition memory (the Remember/Know procedure and the use of receiver operating characteristics to distinguish familiarity and recollection), provide evidence for a selective sparing of the familiarity component of recognition. The dissociation within recognition memory supports dual-process models of recognition, and also supports proposals that anatomically linked regions within the medial temporal lobe make qualitatively different contributions to recognition.
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PMID:Sparing of the familiarity component of recognition memory in a patient with hippocampal pathology. 1615 57

A prominent cognitive impairment after traumatic brain injury (TBI) is hippocampal-dependent memory loss. Although the histopathologic changes in the brain are well documented after TBI, the underlying biochemical mechanisms that contribute to memory loss have yet to be thoroughly delineated. Thus, we determined if calcium/calmodulin-dependent protein kinases (CaMKs), known to be necessary for the formation of hippocampal-dependent memories, are regulated after TBI. Sprague-Dawley rats underwent moderate parasagittal fluid-percussion brain injury on the right side of the parietal cortex. The ipsilateral hippocampus and parietal cortex were Western blotted for phosphorylated, activated alpha-calcium/calmodulin-dependent protein kinase II (alpha-CaMKII), CaMKIV, and CaMKI. alpha-Calcium/calmodulin-dependent protein kinase II was activated in membrane subcellular fractions from the hippocampus and parietal cortex 30 mins after TBI. CaMKI and CaMKIV were activated in a more delayed manner, increasing in phosphorylation 1 h after TBI. The increase in activated alpha-CaMKII in membrane fractions was accompanied by a decrease in cytosolic total alpha-CaMKII, suggesting redistribution to the membrane. Using confocal microscopy, we observed that alpha-CaMKII was activated within hippocampal neurons of the dentate gyrus, CA3, and CA1 regions. Two downstream substrates of alpha-CaMKII, the AMPA-type glutamate receptor GluR1, and cytoplasmic polyadenylation element-binding protein, concomitantly increased in phosphorylation in the hippocampus and cortex 1 h after TBI. These results demonstrate that several of the biochemical cascades that subserve memory formation are activated unselectively in neurons after TBI. As memory formation requires activation of CaMKII signaling pathways at specific neuronal synapses, unselective activation of CaMKII signaling in all synapses may disrupt the machinery for memory formation, resulting in memory loss after TBI.
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PMID:Activation of calcium/calmodulin-dependent protein kinases after traumatic brain injury. 1657 77


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