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At least 685 records · Page 38Linked to original sources
PubMed2004

Antigen-specific CD4 T cell clonal expansion and differentiation in the aged lymphoid microenvironment. II. The memory T cell response is diminished.

We investigated the ability of the aged host environment to support a memory CD4 T cell response to a secondary immunization with a specific antigen. Using an adoptive transfer model, we previously reported that young CD4 T cells, transferred into the young or the aged lymphoid microenvironment, clonally expand and differentiate in a similar fashion after primary immunization with a specific antigen. In this report, we have monitored the clonal expansion of the donor-derived memory CD4 T population following a secondary challenge with the specific antigen. We show that antigen-specific memory T cell clonal expansion is diminished in the aged hosts. However, upon in vitro re-stimulation, antigen-specific CD4 T cells isolated from young and from aged hosts were equally responsive to antigen, thus indicating an inhibitory effect in the aged host environment. We provide evidence that factors specifically present in previously immunized aged hosts must be responsible for the diminished response of otherwise functional, antigen-specific memory CD4 T cells. Our results suggest that the decline in immunologic memory to foreign antigens may be due not only to intrinsic defects in aged T cells, but also to age-related differences in the lymphoid microenvironment of previously immunized hosts.

Adoptive Transfer↗
PubMed1999

Memory T lymphocytes.

Immunological memory protects organisms from recurrent challenge by pathogens. The persistence of a heightened reactive state initiated by antigenic challenge is mediated by long-lived memory lymphocytes. The survival of memory T cells is thought to require stimulation through the T cell receptor (TCR), sometimes by persistent antigen. However, memory T cells can survive in the absence of antigen, in which case TCR stimulation provided by cell surface self-peptide/ major histocompatibility complex (MHC) molecules and cytokines are required to sustain memory T cells. Recent work using mouse models has provided insights into the origin of memory T cells. Understanding the mechanisms that underlie the differentiation and persistence of memory T cells may improve the effectiveness of vaccines through the induction of T cell memory.

Animals↗
PubMed1993

Ontogeny is different for explicit and implicit memory in humans.

This study was aimed to clarify in how far ontogenetic development is different for declarative/explicit compared to procedural/implicit learning. These two memory subsystems are differentially affected in a number of pathological conditions. Sixty-one children between the age of 5 and 10 years were tested on a verbal story recall and non-verbal pictorial recall task, representing explicit memory. To test for implicit memory, a motor mirror tracking task and a non-motor tower-of-hanoi puzzle were used. Both explicit memory tasks showed a clear developmental profile with an increase in the number of recalled items for immediate, late and delayed recall with adult values not reached before the age of 9-10 years. In contrast, there were no age differences for both implicit memory tasks. The study demonstrates that explicit and implicit memory follow different maturational trends and further corroborate the notion of two different memory systems.

Adolescent↗
PubMed2005

Role of circulating androgen levels in effects of apoE4 on cognitive function.

Compared with apoE2 and E3, apoE4 increases the risk of cognitive impairments and of developing Alzheimer's disease (AD). ApoE4 interacts with female sex, further increasing AD risk. Previously, we showed that female Apoe-/- mice are more susceptible to apoE4-induced cognitive deficits than male mice. Androgens protect against these deficits and apoE4 male mice are more sensitive to acute blockade of androgen receptors than apoE3 male mice. To determine the chronic effects of reduced circulating androgen levels on susceptibility to the effects of apoE4 on cognitive function in males, we castrated and sham-castrated apoE4, apoE3, and Apoe-/- male mice and behaviorally compared them 3 months later. Castration impaired novel location recognition in apoE4, but not apoE3 or Apoe-/-, mice. In contrast, castration impaired novel object recognition and spatial memory retention in the water maze in Apoe-/-, but not apoE3 or apoE4, mice. On the contrary, castrated, but not sham-castrated, apoE4 mice showed improved acquisition over the first two hidden platform sessions and spatial memory retention in the first probe trial. While apoE3 and Apoe-/- mice increased their exploratory times with the objects in the trial with the novel object, apoE4 mice did not. ApoE4 mice required more trials than apoE3 or Apoe-/- mice to reach criterion during passive avoidance training, but castration did not modulate passive avoidance learning or memory. Thus, androgens have differential roles in object recognition and spatial learning and memory in the water maze, depending on whether or not apoE4 is present.

Analysis of Variance↗
PubMed1999

Errorless learning and the cognitive rehabilitation of memory-impaired schizophrenic patients.

BACKGROUND: In recent years, evidence has accumulated that a significant proportion of schizophrenic patients have severe memory impairment, which cannot be attributed to the effects of medication, chronicity or institutionalization. Our group has demonstrated that memory impairment is associated with poor psychosocial outcome and treatment resistance. Work on the classical amnesic syndrome has suggested that memory training is facilitated by adopting an 'errorless learning' approach, where subjects do not experience failure during learning. This is based on the theory that the preserved implicit memory of amnesic patients results in implicitly remembered incorrect responses interfering with target items, in the absence of a functioning explicit memory system to allow differentiation. METHOD: We compared three groups of subjects, memory-impaired schizophrenic patients, memory unimpaired schizophrenic patients and healthy controls. RESULTS: An errorless learning approach conferred a significant advantage on the memory-impaired schizophrenic group, bringing their performance up to the level of both control groups. In contrast, adopting a traditional trial and error, or errorful approach resulted in markedly impaired performance in the memory-impaired schizophrenic group only. CONCLUSIONS: We conclude that errorless learning approaches may be worthy of further evaluation in the cognitive rehabilitation of memory-impaired schizophrenic patients.

Adult↗
PubMed2002

Multiple inputs to episodic memory: words tell another story.

Seven patients with semantic dementia were asked to recall and recognize 10-word lists of object-name vocabulary preselected as either still "known" (correct picture naming and word-picture matching) or now "unknown" (incorrect picture naming and word-picture matching) to each individual patient. The patients showed a significant advantage for known words in immediate free recall after several learning trials and also in delayed recall and recognition. The majority of errors of commission for known words were semantic, whereas phonological errors, especially blends of target words, were produced in the unknown condition. These findings support claims that (a) multiple inputs from semantic and perceptual systems support episodic memory and (b) success in verbal and nonverbal episodic memory tasks is differentially dependent on semantic and perceptual information.

Aged↗
PubMed1997

ERPs to encoding and recognition in two different inter-item association tasks.

EVENT-RELATED potentials were obtained during study and recognition of word pairs in an incidental learning paradigm. Word pairs were studied either by performing a semantic judgment separately for each word (non-associative encoding) or by creating a semantic association between the two words (associative encoding). Only word pairs encoded associatively elicited a reliable dm-effect with a right frontal maximum. Recognition of previously studied word pairs revealed two topographically and temporally distinct old/new effects: an earlier parietal effect which was only reliable for associatively encoded items and a right frontal effect which was of equal magnitude for word pairs from both encoding tasks. The findings suggest that ERP effects of distinct memory processes are differentially influenced by the encoding instructions.

Adult↗
PubMed1983

Selective adjustment of the speed of internal clock and memory processes.

Four experiments studied the scaling of time by rats. The purpose was to determine if internal clock and memory processes could be selectively adjusted by pharmacological manipulations. All of the experiments used a temporal discrimination procedure in which one response ("short") was reinforced following a 2-sec noise signal and a different response ("long") was reinforced following an 8-sec noise signal; unreinforced signals of intermediate duration were also presented. The proportion of "long" responses increased as a function of signal duration. All drugs were administered intraperitoneally (ip) and their effect on clock or memory processes was inferred from the observed pattern of change in the point of subjective equality of the psychophysical functions under training and testing conditions. Experiment 1 demonstrated that methamphetamine (1.5 mg/kg) can selectively increase clock speed and that haloperidol (.12 mg/kg) can selectively decrease clock speed. Experiment 2 demonstrated that footshock stress (.2 mA) can selectively increase clock speed during continuous administration but leads to a decrease in clock speed below control values when the footshock is abruptly terminated. Experiment 3 demonstrated that vasopressin (.07 pressor units/kg) and oxytocin (.02 pressor units/kg) can selectively decrease the remembered durations of reinforced times, which suggests that memory storage speed increased. Experiment 4 demonstrated that physostigmine (.01 mg/kg) can selectively decrease the remembered durations of reinforced times and that atropine (.05 mg/kg) can selectively increase these remembered durations, which suggests that memory storage speed was differentially affected. The conclusion is that internal clock and memory processes can be dissociated by selectively adjusting their speed of operation and that these changes can be quantitatively modeled by a scalar timing theory.

Animals↗
PubMed2006

How children suffering severe amnesic syndrome acquire new concepts?

Recent studies revealed that children with developmental amnesia acquired new semantic information. However, they failed to investigate the growth of such knowledge during childhood, and they did not bring evidence concerning the putative role of residual episodic memory in semantic acquisition. This prospective study sought to clarify this issue by assessing both semantic and episodic memory in two amnesic children (RH and KF) with different neuropsychological profiles. We thus applied errorless semantic learning and vanishing cues methods, together with assessments of episodic memory using original recognition tasks within the same protocol. Results demonstrated learning and long-lasting maintenance of multicomponent concepts (comprising labels, categories and features) in both amnesic children. Importantly, episodic memory assessments revealed differential residual abilities in these children, which may account for their respective profiles of semantic acquisition. Thus, RH, who demonstrated residual episodic abilities, acquired normally. However, the learning of KF, who had a massive impairment of episodic memory, remained slower than her controls. In conclusion, even though an episodic impairment may slacken new semantic learning, our research provides new evidence for the de novo acquisition of semantic concepts in childhood amnesic syndrome and strengthens the idea that semantic learning can occur without any recruitment of episodic memory.

Amnesia↗
PubMedDate not supplied

Differential induction of long-term synaptic facilitation by spaced and massed applications of serotonin at sensory neuron synapses of Aplysia californica.

Serotonin (5HT)-induced facilitation of synaptic transmission from tail sensory neurons (SNs) to motor neurons (MNs) in the marine mollusc Aplysia provides a cellular model of short- and long-term memory for behavioral sensitization of the tail withdrawal reflex. Synaptic facilitation at these synapses occurs in three temporal phases: short-term (STF, lasting minutes), intermediate-term (ITF, lasting more than an hour), and long-term (LTF, lasting >24 hr). STF, ITF, and LTF differ in their induction requirements: A single brief exposure of 5HT induces STF, whereas five applications are required for ITF and LTF. Moreover, STF and LTF can be induced independently. Different forms of memory often show differential sensitivity to the pattern of training trials. To begin to explore this effect at a cellular level, we examined ITF and LTF induced by one of two patterns of 5HT application: a spaced pattern (five 5-min exposures with an interval of 15 min) or a massed pattern (one continuous 25-min application). The spaced and massed patterns both induced ITF; however, spaced 5HT application was significantly more reliable at inducing LTF than was massed application. Thus, whereas induction of ITF and LTF require similar amounts of 5HT, the cellular mechanisms underlying the induction of LTF are more sensitive to the pattern of the induction trials. In the massed group, further analysis revealed a relationship between the expression of ITF and the subsequent expression of LTF, suggesting that these two processes may be mechanistically related.

Animals↗
PubMed2003

Genetic reprogramming of primary human T cells reveals functional plasticity in Th cell differentiation.

Activation of naive T cells through the TCR and cytokine signals directs their differentiation into effector or memory subsets with different cytokine profiles. Here, we tested the flexibility of human Th1 or Th2 differentiation by forced expression of transcription factors T-bet and GATA-3. Ectopic expression of T-bet and GATA-3 in freshly isolated human T(N) cells resulted in their differentiation to a Th1 and Th2 phenotype, respectively, in the absence of polarizing cytokines. Introduction of GATA-3 into lineage-committed Th1 cells induced the expression of Th2-specific cytokines (IL-4 and IL-5) and chemotactic receptors (CCR4, chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2). However, these cells partially maintained their Th1-specific profile (IFN-gamma and IL-12Rbeta2 expression). Conversely, expression of T-bet in lineage-committed Th2 cells caused a more profound switch to the Th1 phenotype, including the up-regulation of CXCR3 and down-regulation of CCR4 and CRTH2. Interestingly, similar to the naive T cell subset, central memory T cells were also largely programmed toward Th1 or Th2 effector cells upon expression of T-bet and GATA-3, respectively. However, expression of these transcription factors in effector memory T cells was much less influential on cytokine and chemokine receptor expression profiles. Our results reveal remarkable plasticity in the differentiation programs of human memory T cells. This flexibility is progressively diminished as cells mature from naive to effector T cells. These findings have important implications in understanding the molecular mechanisms of human T cell differentiation and for devising novel therapeutic strategies aimed at immunomodulation of skewed effector T cell responses.

Adult↗
PubMed2006

T cell memory and protective immunity by vaccination: is more better?

Protection against intracellular pathogens or tumor antigens requires T-cell mediated responses. Recently, it has become apparent that protection against disease correlates with T cells of the central memory type in many instances. Here, we analyze current data to distill a set of rules for the induction and maintenance of central memory T-cell responses. Recent studies show that T-cell help and the lack of overt inflammation at the time of priming are prerequisite for the induction, maintenance and expansion of memory T cells. Central to our hypothesis is that, in addition to these factors, successful vaccination in the immunologically inexperienced individual should be based on low antigen dose, to decelerate replicative senescence in responding cells and favor lineage differentiation of central memory T cells. In the immunologically experienced individual, it will be necessary, in addition, to abate the antigen load in plasma before vaccination. These guiding principles might help to raise improved protective T-cell responses by vaccination in humans.

Animals↗
PubMed1992

Rapid speech processing and divided attention: processing rate versus processing resources as an explanation of age effects.

The authors conducted a dual-task study to examine age differences in speech processing under varying loads. Younger and older adults listened to and immediately recalled spoken passages presented at various speech rates (140-280 words per min). This task was performed alone as well as in a divided-attention condition in which subjects concurrently performed a picture recognition task. Consistent with the slowing hypothesis, older adults' immediate memory performance was differentially depressed when speech rates were very fast. The Age x Speech Rate interaction, however, was not exacerbated in the divided-attention condition. This suggests that aging may reduce the rate at which the processing operations underlying memory for speech are completed, but this is conceptually distinct from an age-related reduction in attentional capacity.

Adolescent↗
PubMed1994

An 18FDG-PET study of cortical activation during a short-term visual memory task in humans.

Studies of subhuman primates and man have shown that the prefrontal cortex is important for spatial working memory. We have used 18fluorodeoxyglucose positron emission tomography (18FDG-PET) to study a non-spatial, abstract visual memory task of in man. Using a regions-of-interest approach with discriminant analysis of the relative regional cerebral metabolic rate of glucose consumption (rCMRGlc), we found that changes in dorsal prefrontal, premotor/motor frontal and posterior cingulate areas differentiated the primary memory task from the control task. Less robust increases in glucose uptake were observed in lateral parietal cortex, while some subcortical and limbic regions showed decreases. This is the first activation study with a non-spatial, visual task. These results complement previous studies in that they substantiate the role of the prefrontal cortex in the mediation of cross-temporal contingencies of behavior, and point to a role of the premotor region in this mediation as well.

Adult↗
PubMed1999

Source memory in major depression.

BACKGROUND: Research demonstrating episodic memory deficits in clinical depression has dealt with item memory exclusively. The present research sought to determine whether memory for source is differentially affected by depression. METHODS: Patients with major depression and normal control subjects were examined in item memory and two types of source memory, requiring discriminations between (e.g. something that the subject said and something another person said) and within (e.g. something that one person said and something another person said) classes. RESULTS: Depression-related deficits in item memory were exacerbated in source memory. However, deficits in source memory in depressed patients were restricted to those conditions requiring within-class discriminations. CONCLUSION: The overall pattern of results may reflect that those symptoms of major depression that affect the individuals basic processing resources (e.g. concentration difficulties, lack of effort, loss of energy) results in an impairment of episodic memory, particularly when the demands of differentiating perceptual and cognitive information are high.

Adult↗
PubMed2005

Nature of stress: differential effects on brain acetylcholinesterase activity and memory in rats.

Effect of acute, chronic-predictable and chronic-unpredictable stress on memory and acetylcholinesterase (AChE) was investigated in rats. The animals were subjected to 3 type of stressors--(1) acute immobilization stress, (2) chronic-predictable stress i.e., immobilization daily for 5 consecutive days and (3) chronic-unpredictable stress that included reversal of light/dark cycle, over-night fasting, forced-swimming, immobilization and forced exercise in random unpredictable manner daily for 5 consecutive days. Learning and memory function was studied by single trial Passive avoidance test. AChE activity was assayed spectrophotometrically in the detergent (DS) and salt (SS) soluble fractions in different brain regions. Learning was obtained in acute and chronic-predictable stress groups but not in chronic-unpredictable group. Acute, chronic-predictable and chronic-unpredictable stress caused significant decrease in AChE activity in the DS fraction of cortex, hippocampus and hypothalamus as compared to control. Results indicate that AChE in DS fraction is predominantly affected in stressed and stressed-trained group but cognition is affected only by chronic-unpredictable stress. In acute and chronic-predictable groups the decreased AChE activity in the hippocampal DS fraction during learning may be responsible to maintain cognitive function by enhancing the cholinergic activity.

Acetylcholinesterase↗