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Scopolamine differentially affects memory of 8- and 16-month-old rats in the double Y-maze.

The present study investigated the effects of scopolamine on working and reference memory in the same rats at 8 and 16 months of age. Rats were trained in the double Y-maze until a criterion of > or = 88% correct was reached on both memory components. Doses of scopolamine (0.1, 0.4, 0.8 mg/kg for rats at 8 months; 0.05, 0.1, 0.4 mg/kg for rats at 16 months) were administered in a counterbalanced order 30 min before test sessions which also included delays of 0, 5, or 30 s prior to both memory components. Results showed that at both ages the 0.1 mg/kg scopolamine dose selectively impaired working memory, whereas higher doses impaired both working and reference memory. Delays selectively decreased working memory choice accuracy and enhanced the effect of scopolamine. Rats at 16 months performed less well on both reference and working memory and showed greater impairments with scopolamine and delays. The present findings support the hypothesis that a decrease in cholinergic neurotransmission contributes to age-related memory deficits.

Aging↗

Antiepileptic drugs and memory.

Impaired memory is among the most common complaints of patients with epilepsy. Multiple factors contribute to memory impairment in patients with epilepsy. Thus, delineation of the effects of antiepileptic drugs (AEDs) on memory in clinical populations faces methodological difficulties. Further, subjective perception of memory problems by patients is influenced by mood. However, there is evidence from animal and healthy volunteer studies supporting an independent potential for AEDs to impair memory. Differential AED effects on memory have been observed, and AED effects may interact with focal brain lesions. Memory impairment from AEDs is a greater concern at the age extremes, although the effects of AEDs, especially the newer agents, have not been thoroughly studied in these populations. Well-controlled studies are needed to understand the underlying mechanisms and to further delineate the magnitude and relative effects of AEDs on memory.

Aged↗

Differentiating between memory and interpretation biases in socially anxious and nonanxious individuals.

Although individual cognitive biases toward threat in social anxiety are well established, few studies have examined the manner in which cognitive biases work in conjunction. In the present study, socially anxious ( n = 54 ) and nonanxious ( n = 58 ) individuals read 10 passages consisting of positive social or evaluative, negative social or evaluative, and neutral content and completed two cognitive tasks assessing memory of factual details and interpretation immediately and after 48 h. Socially anxious and nonanxious individuals did not differ in their memory for details presented in the passages. However, they made less positive and more negative interpretations of details included in the passages, particularly in positive passages that were self-relevant and particularly in positive passages after the delay. After including depression, state anxiety, and trait anxiety as covariates, biased interpretation of positive passages after the time delay remained significant, but biased interpretation of the self-relevant, positive passages did not. It is concluded that socially anxious individuals are characterized by accurate memory of threatening, factual material, but that they impose a biased interpretation upon that material, especially after some time has passed.

Adult↗

Differential memory-preserving effects of reminders at 6 months.

Although reactivation and reinstatement reminders differ procedurally, differences in their memory-preserving effects have been described as artifactual. In three experiments, we examined this conclusion. One hundred and twelve 6-month-olds learned an operant task, forgot it, received a reactivation or reinstatement reminder to recover the inactive memory, and were tested after increasing delays until they forgot it again. In Experiments 1a and 1b, a single reactivation reminder extended infants' memory of an operant mobile task for 2 weeks after reminding, but a single reinstatement extended it for 4 weeks, when testing was discontinued. In Experiment 2, a single reinstatement extended 6-month-olds' memory of an operant train task for 19 weeks after reminding, when infants were almost 1 year old. After reactivation, infants remember this task for only 2 weeks. The finding that the memory-preserving effect of reinstatement is greater by an order of magnitude suggests that procedural differences between the two reminders have functional significance.

Adolescent↗

On the differentiation of memory beliefs from memory knowledge: the factor structure of the Metamemory in Adulthood Scale.

This study was designed to test the hypothesis that there are multiple factors of metamemory present in the Metamemory in Adulthood (MIA) questionnaire. Data on seven MIA scales from six separate studies on memory/metamemory relationships (total N = 750) were combined to yield two half-samples for cross-validation purposes. The samples were partitioned into young, middle-aged, and old groups. A multiple group confirmatory factor analysis was then conducted on the data, using the first half sample to develop a model and the second half sample to validate it. Although the models did not fully cross-validate, both analyses indicated that there are at least two higher-order factors in the MIA. The first involves beliefs about self-efficacy in using memory. The second factor combines knowledge about memory and affect concerning memory (e.g., achievement motivation). The analyses also indicated that the factor loadings for the second factor, tentatively labelled Knowledge, were invariant across the three age groups, but that there were age differences in the Self-Efficacy Beliefs factor loadings. The differences were localized to age-related increases in the loadings for the MIA Change and Locus scales. The two factor solution has potential for resolving conflicting results in the literature regarding age differences in both metamemory and metamemory/memory performance relationships.

Adult↗

Differentiating between memory and effector CD8 T cells by altered expression of cell surface O-glycans.

Currently there are few reliable cell surface markers that can clearly discriminate effector from memory T cells. To determine if there are changes in O-glycosylation between these two cell types, we analyzed virus-specific CD8 T cells at various time points after lymphocytic choriomeningitis virus infection of mice. Antigen-specific CD8 T cells were identified using major histocompatibility complex class I tetramers, and glycosylation changes were monitored with a monoclonal antibody (1B11) that recognizes O-glycans on mucin-type glycoproteins. We observed a striking upregulation of a specific cell surface O-glycan epitope on virus-specific CD8 T cells during the effector phase of the primary cytotoxic T lymphocyte (CTL) response. This upregulation showed a strong correlation with the acquisition of effector function and was downregulated on memory CD8 T cells. Upon reinfection, there was again increased expression of this specific O-glycan epitope on secondary CTL effectors, followed once more by decreased expression on memory cells. Thus, this study identifies a new cell surface marker to distinguish between effector and memory CD8 T cells. This marker can be used to isolate pure populations of effector CTLs and also to determine the proportion of memory CD8 T cells that are recruited into the secondary response upon reencounter with antigen. This latter information will be of value in optimizing immunization strategies for boosting CD8 T cell responses.

Animals↗

Differential working memory impairment in bipolar disorder and schizophrenia: effects of lifetime history of psychosis.

BACKGROUND: Although bipolar disorder and schizophrenia have long been viewed as distinct illnesses, there is growing evidence that these two complex diseases share some common genes, which may manifest as overlapping neuropsychological impairments. Although working memory dysfunction has been proposed to be central to the pathophysiology of schizophrenia, it has received less attention in studies of bipolar disorder. METHOD: We applied measures of working memory to patients with schizophrenia (n = 15), patients with schizoaffective disorder (n = 15), patients with psychotic (n = 11) and non-psychotic (n = 15) bipolar disorder, and demographically matched healthy subjects (n = 32), in order to determine the extent to which these groups show common or unique impairments. RESULTS: While patients with bipolar disorder (with and without psychotic features) and those with schizophrenia/schizoaffective disorder were impaired on backward digit span, only patients with a lifetime history of psychotic features, regardless of diagnosis, were impaired on spatial delayed response task. CONCLUSIONS: Backward digit span performance is comparable in bipolar disorder and schizophrenia, and may be an appropriate endophenotypic marker that cuts across diagnostic categories. In contrast, spatial working memory performance clearly distinguishes non-psychotic bipolar disorder patients from patients with functional psychosis.

Adult↗

[Characteristics of the conditions for memory cell differentiation--the initial and enriched precursors of secondary cytotoxic T-lymphocytes (pCTL-2) specific for the histocompatibility class I molecule].

The in vivo induced pCTL-2 with phenotype L3T4- Lyt2- specific to the H-2Kb molecule, turn into effector CTL during 4 days in the mixed lymphocyte culture (with heat-treated donor stimulators) much more efficiently when donor and recipient are different from one another not only in MHC class I (anti-BIO, MBR BIO.AKM) but in I + II (Kb + Ib) ahti-C57BL/6 BIAD2(RIOI). The initial pCTL-2 differentiation in enhanced as a result of synergistic effect between the Kb alloantigen and rIL2. The anti-Kb pCTL-2, being separated from helper T cells by means of absorption onto the macrophage donor monolayer and elution from it, give rise to pronounced differentiation in simplified conditions, irrespective of the stimulator presence and without external rIL2. It is supposed that these phenomena are raised to secretion of the CTL differentiation factor by the eluted pCTL-2 themselves, and besides, rIL2 may promote for secretion of this factor additionally.

Animals↗

Switch in chemokine receptor phenotype on memory T cells without a change in the cytokine phenotype.

Th1 and Th2 cells as defined by their cytokine profile are associated with the expression of the chemokine receptors CCR5 and CCR3, respectively. In committed human memory Th1 cells the cytokine profile is irreversibly expressed. However, it is not known if the chemokine receptor phenotypes of Th1 and Th2 cells are permanently associated to the cytokine profile or if it can be changed. To analyze the possibility of inducing a switch in chemokine receptor phenotype on memory Th cells we used differentiated memory Th cells isolated from synovial tissue (ST) samples of patients with rheumatoid arthritis (RA). Freshly isolated T cells, T-cell lines and T-cell clones from these tissues were manipulated with Th1 (interleukin (IL)-12 + anti IL-4) or Th2 (IL-4 + anti IL-12) inducing conditions. The surface expression of CCR5 and CCR3 was analyzed by flowcytometry and interferon (IFN)-gamma and IL-4 production by ELISA. A Th1-inducing cytokine environment increased the expression of CCR5 in Th1 cells and induced the expression of CCR5 in Th2 cells as compared to culture condition with only IL-2. Induction of CCR5 expression on Th2 clones was associated with secretion of some IFN-gamma. Moreover, the Th2-associated chemokine receptor CCR3 could be expressed on both Th1-dominant cell lines, and clones of Th1 and Th0 type after culture conditions with IL-4. This expression of CCR3 was associated with a reduced IFN-gamma production, but no IL-4 production could be induced. The IL-4-treated Th1 clones had a reduced migratory capacity against chemokines produced by ST cells compared to nonmanipulated T-cell clones. In contrast, the same IL-12-treated Th1 clones showed an increased migratory potential. Induction of the Th2-associated marker CCR3 on memory Th1 cells demonstrates that a change in chemokine receptor phenotype related to the Th2 type can be induced on terminally differentiated Th1 cells, without a change in the cytokine profile.

Arthritis, Rheumatoid↗

Cutting edge: gut microenvironment promotes differentiation of a unique memory CD8 T cell population.

Whether tissue microenvironment influences memory CD8 T cell differentiation is unclear. We demonstrate that virus-specific intraepithelial lymphocytes in gut resemble neither central nor effector memory CD8 T cells isolated from spleen or blood. This unique phenotype arises in situ within the gut, suggesting that anatomic location plays an inductive role in the memory differentiation program. In support of this hypothesis, memory CD8 T cells changed phenotype upon change in location. After transfer and in vivo restimulation, gut or spleen memory cells proliferated, disseminated into spleen and gut, and adopted the memory T cell phenotype characteristic of their new environment. Our data suggests that anatomic location directly impacts the memory T cell differentiation program.

Animals↗

Functional plasticity of an antigen-specific memory CD4 T cell population.

The protective nature of memory immune responses is attributed largely to terminally differentiated memory T cells that retain memory of the antigen via the antigen receptor and memory of the effector functions that initially cleared the pathogen. It is not known whether a given population of antigen-specific memory T cells is endowed with functional flexibility to provide protective responses against antigens reencountered in different immunological contexts. Here, we examine functional properties of influenza hemagglutinin (HA)-specific memory CD4 T cells recovered from adoptive hosts that received in vitro-activated HA-specific T cell receptor-transgenic CD4 T cells 2 months to 1 year previously. We demonstrate that this HA-specific memory CD4 T cell population bearing a clonal T cell receptor can produce predominantly T helper 1 or T helper 2 effector cytokines depending on the nature of the recall stimulus. Our findings reveal remarkable functional plasticity within an antigen-specific memory T cell population and have direct implications for modulating memory T cell function in vaccine design and treatments for autoimmune diseases.

Adoptive Transfer↗

Increased HTLV type 1 tax specific CD8+ cells in HTLV type 1-asociated myelopathy/tropical spastic paraparesis: correlation with HTLV type 1 proviral load.

Less than 1% of individuals infected with the human T lymphotropic virus type 1 (HTLV-1) develop an inflammatory neurological disorder, termed HTLV-1-associated myelopathy/tropical spastic (HAM/TSP), while the vast majority of those infected remain asymptomatic HTLV-1 carriers (ACs). The fundamental viroimmunological differences between these groups are not well understood. To address this issue, we have investigated HTLV-1-specific T cell responses and measured the proviral load in these groups. Frequencies of HTLV-1-specific CD8(+) cells were demonstrated to be significantly higher in HAM/TSP patients than in ACs by using intracellular cytokine staining and soluble divalent HLA-A2/Ig fusion protein loaded with HTLV-1 Tax 11-19 peptide. It is consistent with the observed increase in HTLV-1-specific cytotoxic T lymphocytes in HAM/TSP patients. These CD8(+) cells produced interferon (IFN)-gamma in recognition of HTLV-1 antigens bound to HLAs on the infected CD4(+) cells. Using phenotypic markers indicative for T cell differentiation, memory and/or effector HTLV-1 Tax-specific CD8(+) cells were found to be increased in HLA-A2 HAM/TSP patients. HTLV-1 proviral load was elevated in HAM/TSP patients when compared to ACs. In addition, the proviral load in HAM/TSP patients correlated with the frequency of HTLV-1-specific IFN-gamma(+)CD8(+) cells or Tax-HLA-A2/Ig(+)CD8(+) cells, especially with the effector cells. In contrast, the proviral load inversely correlated with memory cells. These results suggest that HTLV-1 antigens may continuously stimulate HTLV-1-specific CD8(+) cells and differentiate them from memory cells into effector cells in vivo. These differentiated HTLV-1-specific CD8(+) cells may play a role in the pathogenesis of HAM/TSP.

CD8-Positive T-Lymphocytes↗

Individual differences in children's memory and reading comprehension: an investigation of semantic and inhibitory deficits.

Three experiments compared the verbal memory skills of children with poor reading comprehension with that of same-age good comprehenders. The aims were to determine if semantic and/or inhibitory deficits explained comprehenders' problems on measures of verbal short-term memory and verbal working memory. In Experiment 1 there were no group differences on word- and number-based measures of short-term storage and no evidence that semantic knowledge mediated word recall. In Experiment 2 poor comprehenders were impaired on word- and number-based assessments of working memory, the greatest deficit found on the word-based task. Error analysis of both word-based tasks revealed that poor comprehenders were more likely to recall items that should have been inhibited than were good comprehenders. Experiment 3 extended this finding: Poor comprehenders were less able to inhibit information that was no longer relevant. Together, these findings suggest that individual differences in inhibitory processing influence the ability to regulate the contents of working memory, which may contribute to the differential memory performance of good and poor comprehenders.

Child↗

Use of memory tests in differentiating organic disorder from depression.

Although memory tests are commonly used to help differentiate organic conditions from depression, the extent to which depression might influence test performance is unclear. Comparison of the performances of normal, brain-damaged, and depressed subjects on a battery of verbal and visual memory tests revealed that the incidence of impairment amongst the depressed subjects was not significantly greater than amongst normal subjects on the majority of measures, and that within the depressed group, the degree of depression was not related to poor test performance. The brain-damaged group displayed a significant incidence of impairment on all measures, and a significantly greater incidence than the depressed group on the majority of measures. It is concluded that memory tests have a useful role to play in differential diagnosis.

Adolescent↗

Ecological validity of list-learning tests and self-reported memory in healthy individuals and those with temporal lobe epilepsy.

We evaluated in patients with temporal lobe epilepsy (TLE) and healthy volunteers whether list-learning tests of episodic verbal/figural memory and subjective self-reports reliably indicate "Memory in Reality" (MIR). MIR was assessed by the incidental memory of the neuropsychological test event one week after testing. Subjective Memory was assessed by a questionnaire (SMQ). Patients achieved poorer results than controls in all measures of memory. Correlation and multiple regression analysis indicates that list-learning is highly predictive regarding performance in MIR. MIR predominantly relied on verbal memory in patients and on visual/figural memory in controls. Subjective memory differentiated patients and controls but it correlated to MIR only in subjects with unimpaired memory. In conclusion, the data indicate a high ecological validity of list-learning paradigms and they seriously question the diagnostic value of self-reported memory. They also indicate that incidentally acquired knowledge might be differentially represented in patients with a memory disorder and healthy persons.

Adult↗

Cutting edge: a single MHC class Ia is sufficient for CD8 memory T cell differentiation.

Recent studies have suggested a role for MHC class Ib molecules in providing signals for memory T cell differentiation during the early phases of acute infection. To test this hypothesis, we assessed the development of effector and memory CD8 T cells in transgenic mice expressing a single chain H-2D(d)/beta2-microglobulin (beta2M) fusion protein on a beta2M-deficient background. These mice thus express a single MHC class Ia in the absence of all other beta2M-dependent class Ia and Ib molecules. Following infection with a recombinant vaccinia virus expressing a known D(d)-restricted epitope from HIV-1 gp160, the development of effector and memory cells CD8 T cells was comparable to control mice. Furthermore, these memory cells responded rapidly and robustly to antigenic restimulation. Therefore, we conclude that full CD8 memory differentiation requires only a single MHC class Ia chain, ruling out a requirement for MHC class Ib molecules in this process.

Animals↗

Molecular and functional profiling of memory CD8 T cell differentiation.

How and when memory T cells form during an immune response are long-standing questions. To better understand memory CD8 T cell development, a time course of gene expression and functional changes in antigen-specific T cells during viral infection was evaluated. The expression of many genes continued to change after viral clearance in accordance with changes in CD8 T cell functional properties. Even though memory cell precursors were present at the peak of the immune response, these cells did not display hallmark functional traits of memory T cells. However, these cells gradually acquired the memory cell qualities of self-renewal and rapid recall to antigen suggesting the model that antigen-specific CD8 T cells progressively differentiate into memory cells following viral infection.

Animals↗

Distinct lineages of T(H)1 cells have differential capacities for memory cell generation in vivo.

We studied here the long-term maintenance of distinct populations of T helper type 1 (T(H)1)-lineage cells in vivo and found that effector T(H)1 cells, defined by their secretion of interferon-gamma (IFN-gamma), are short-lived and do not efficiently develop into long-term memory T(H)1 cells. In contrast, a population of activated T(H)1-lineage cells that did not secrete IFN-gamma after primary antigenic stimulation persisted for several months in vivo and developed the capacity to secrete IFN-gamma upon subsequent stimulation. These data suggest that a linear differentiation pathway, as defined by the transition from IFN-gamma-producing to resting memory cells, is relatively limited in vivo and support a revised model for T(H)1 memory differentiation.

Animals↗