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Results for “memory differentiation”

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PubMed1998

Combination of the different biological markers for increasing specificity of in vivo Alzheimer's testing.

In view of existing drugs (acetylcholine esterase inhibitors) and emerging therapeutic compounds (e.g. neuroprotective and anti-inflammatory compounds), CSF markers would be of great use to improve the clinical diagnostic accuracy of Alzheimer's disease (AD). Correct identification of AD would be especially important early in the course of the disease, when the clinical diagnosis is difficult, and drugs have the greatest potential of being effective. Biochemical markers for AD include ApoE genotyping, where the ApoE epsilon 4 allele has proven to have a high predictive value for AD. Biochemical markers for AD also include several potential cerebrospinal fluid (CSF) markers: beta-amyloid(1-42), possibly reflecting amyloid deposition and formation of senile plaques; PHFtau protein a marker for the phosphorylation state of tau, and formation of neurofibrillary tangles; (total)tau protein, a normal axonal protein, as a marker for ongoing neuronal and axonal degeneration; synaptic vesicle proteins, e.g. synaptotagmin, a synaptic vesicle protein which is found in the CSF, as markers for synaptic activity or degeneration; neuromodulin or growth-associated protein GAP-43, as a marker for synaptic degeneration, and the CSF/serum albumin ratio, as a marker for blood-brain barrier damage, used to exclude patients with concomitant cerebrovascular pathology. However, although CSF markers may identify different pathogenic processes in AD, there is no such process that is specific for AD, and thus little hope of ever finding a single CSF biochemical marker that gives an absolute discrimination between AD and other dementia disorders. Instead, combination of several CSF biochemical markers, each reflecting a pathogenic process, may increase both the sensitivity and specificity. Further, the accuracy of the clinical diagnosis of AD may increase if the diagnosis is based on the summarised information gained from the clinical examination, brain-imaging techniques (SPECT, CT/MRT scans), and biochemical markers. Using this approach, CSF markers have a large potential to help to differentiate AD from the most problematic differential diagnoses, especially age-associated memory impairment, depressive pseudo-dementia, Parkinson's disease, and frontal lobe dementia.

Aged↗
PubMed2005

The role of models in understanding CD8+ T-cell memory.

Immunological memory - the ability to 'remember' previously encountered pathogens and respond faster on re-exposure - is a central feature of the immune response of vertebrates. We outline how mathematical models have contributed to our understanding of CD8(+) T-cell memory. Together with experimental data, models have helped to quantitatively describe and to further our understanding of both the generation of memory after infection with a pathogen and the maintenance of this memory throughout the life of an individual.

Animals↗
PubMed1987

Transient global amnesia. When memory temporarily disappears.

Transient global amnesia is a benign condition of sudden onset that resolves spontaneously. Retrograde amnesia prevents recall of events antedating the episode by hours to years, and anterograde amnesia produces the characteristic features of inability to learn new material and repetitious questioning. Laboratory investigation of these patients is generally unrewarding. Transient global amnesia is easily distinguished from amnesia caused by head trauma or transient ischemic attack, confusional state, and functional amnesia. Although transient global amnesia is most likely caused by transient ischemia of brain structures important for memory, thromboembolic cerebrovascular disease is not the cause. The patient with transient global amnesia should be treated conservatively.

Amnesia↗
PubMed2006

Thymic output and functionality of the IL-7/IL-7 receptor system in centenarians: implications for the neolymphogenesis at the limit of human life.

During aging, the thymus undergoes a marked involution that is responsible for profound changes in the T-cell compartment. To investigate the capacity of the thymus to produce new cells at the limit of human lifespan, we analyzed some basic mechanisms responsible for the renewal and maintenance of peripheral T lymphocytes in 44 centenarians. Thymic functionality was analyzed by the quantification of cells presenting the T-cell receptor rearrangement excision circles (TREC). A new method based upon real-time PCR was used, and we found that most centenarians (84%) had undetectable levels of TREC+ cells. Six-color cytofluorimetric analysis revealed that centenarians had an extremely low number of naïve T cells; central memory and effector memory T cells were greatly increased, while terminally differentiated cells were as numerous as in young (aged 20-45) or middle-aged (aged 58-62) donors. Interleukin (IL)-7 and IL-7 receptor alpha-chain (CD127) levels were the same at all ages, as shown by ELISA, flow cytometry and real-time PCR. However, IL-7 plasma levels were higher in centenarian females than males. The presence of TREC+ cells and of very few naïve T lymphocytes suggests that in centenarians such cells could either derive from residues of thymic lymphopoietic islets, or even represent long-living lymphocytes that have not yet encountered their antigen. IL-7 could be one of the components responsible, among others, for the higher probability of reaching extreme ages typical of females.

Adult↗
PubMed2006

CD4+ T-cell memory: generation and multi-faceted roles for CD4+ T cells in protective immunity to influenza.

We have outlined the carefully orchestrated process of CD4+ T-cell differentiation from naïve to effector and from effector to memory cells with a focus on how these processes can be studied in vivo in responses to pathogen infection. We emphasize that the regulatory factors that determine the quality and quantity of the effector and memory cells generated include (i) the antigen dose during the initial T-cell interaction with antigen-presenting cells; (ii) the dose and duration of repeated interactions; and (iii) the milieu of inflammatory and growth cytokines that responding CD4+ T cells encounter. We suggest that heterogeneity in these regulatory factors leads to the generation of a spectrum of effectors with different functional attributes. Furthermore, we suggest that it is the presence of effectors at different stages along a pathway of progressive linear differentiation that leads to a related spectrum of memory cells. Our studies particularly highlight the multifaceted roles of CD4+ effector and memory T cells in protective responses to influenza infection and support the concept that efficient priming of CD4+ T cells that react to shared influenza proteins could contribute greatly to vaccine strategies for influenza.

Animals↗
PubMed1998

Differential involvement of cortical receptor mechanisms in working, short-term and long-term memory.

Rats received, through bilaterally implanted indwelling cannulae, 0.5 microliter infusions of 6-cyano-7-nitroquinoxaline2,3-dione (CNQX) (0.5 microgram), D-2-amino-5-phophono pentanoic acid (AP5) (5.0 micrograms), muscimol (0.5 microgram), scopolamine (2.0 micrograms), SCH23390 (2.5 micrograms), saline or a vehicle into the CA1 region of the hippocampus, or into the antero-lateral prefrontal (PRE), posterior parietal (PP) and entorhinal cortex (EC). The infusions were given 6 min prior to one-trial step-down inhibitory avoidance training in order to measure their effect on working memory (WM), or immediately post-training in order to measure their effect on short-term (STM) and long-term memory (LTM), 1.5 and 24 h later, respectively. WM was inhibited by CNQX or muscimol given into any of the cortical areas, by SCH23390 given into CA1, PRE or PP, and by scopolamine given into PRE or EC. STM was unaffected by any of the treatments given into PRE, and was inhibited by CNQX or muscimol given into CA1, PP and EC and by scopolamine given into PP, and enhanced by SCH given into CA1. LTM was inhibited by CNQX, muscimol, scopolamine or SCH23390 given into PRE, by scopolamine given into PP, by SCH23390 given into the entorhinal cortex, and by AP5, CNQX, muscimol or scopolamine given into CA1. The results indicate a differential involvement of the various neurotransmitter systems in the three types of memory in the various brain areas, and a separation of the mechanisms and of the regions involved in each. In addition, some of the findings suggested links between WM and LTM processing in PRE, between WM and STM processing in EC and PP, and between all three types of memory in CA1.

Animals↗
PubMed1995

Differentiation and tolerance of CD4+ T lymphocytes.

The development of effector and memory populations of T lymphocytes is determined by antigen-induced growth and differentiation of naive T cells, and it is regulated by antigen-induced functional tolerance and cell death. CD4+ helper T lymphocytes that vary in their profiles of cytokine production and in effector functions also show distinct responses to antigens and co-stimulatory signals, and they differ in their sensitivity to tolerance induction. Thus, stimuli that trigger T cell growth and differentiation, as well as mechanisms that inhibit T cell expansion, determine both the magnitude and the nature of T cell-dependent immune responses to protein antigens.

Animals↗
PubMed2005

Innate signals compensate for the absence of PKC-{theta} during in vivo CD8(+) T cell effector and memory responses.

PKC- is central to T-helper (Th) 2 cell differentiation and effector function; however, its importance for antiviral effector, and in particular memory CD8(+) T cell responses, remains unclear. We have investigated the role of PKC- during in vivo and in vitro responses against influenza virus, lymphocytic choriomeningitis virus, vaccinia virus, and replication-deficient virus-like particles. In the absence of PKC-, antiviral CD8(+) T cells presented an unresponsive phenotype in vitro, which could be restored with exogenous IL-2 or by Toll-like receptor ligand-activated dendritic cells. In striking contrast, PKC- appeared to be superfluous for in vivo antiviral responses irrespective of whether the virus infected systemically, was localized to the lung, or did not replicate. In addition, CD8(+) CCR7-effector memory responses were normal in PKC--deficient mice, both in lymphoid and peripheral tissues. Our data show that increased activation signals delivered in vivo by highly activated dendritic cells, as present during viral infections, overcome the requirement for PKC- during CD8(+) T cell antiviral responses.

Animals↗
PubMed2000

Positive feedback circuits and memory.

The concept of regulatory feedback circuit refers to oriented cyclic interactions between elements of a system. There are two classes of circuits, positive and negative, whose properties are in striking contrast. Positive circuits are a prerequisite for the occurrence of multiple steady states (multistationarity), and hence, they are involved in all processes showing hysteresis or memory. Endogenous or exogenous perturbations can lead the system to exhibit or to evoke one particular stable regime. The role of positive circuits in cell differentiation and in immunology is well documented. Negative circuits are involved in homeostatic regulation, with or without oscillations. The aim of this paper is to show: a) that positive circuits account for many features of memory stricto sensu (i.e., neural memory and mnesic evocation) as well as largo sensu (e.g. differentiation or immunological memory); and b) that simple combinations of positive and negative circuits provide powerful regulatory modules, which can also be associated in batteries. These entities have vast dynamical possibilities in the field of neurobiology, as well as in the fields of differentiation and immunology. Here we consider a universal minimal regulatory module, for which we suggest to adopt the term 'logical regulon', which can be considered as an atom of Jacob's integron. It comprises a positive and a negative circuit in its interaction matrix, and we recall the main results related to the simultaneous presence of these circuits. Finally, we give three applications of this type of interaction matrix. The first two deal with the coexistence of multiple stable steady states and periodicity in differentiation and in an immunological system showing hysteretic properties. The third deals with the dual problems of synchronization and desynchronization of a neural model for hippocampus memory evocation processes.

Cell Differentiation↗
PubMed1990

Scopolamine differentially disrupts the behavior of male and female Wistar rats in a delayed nonmatching to position procedure.

Evidence is available that pharmacological interference with the cholinergic system may disrupt behavior in experimental procedures designed to investigate learning and memory processes. Recently it has been suggested that the cholinergic system may be sexually dimorphic. The present experiment was designed to investigate whether or not manipulation of the cholinergic system differentially affected memory processes in both sexes. Male and female Wistar rats were exposed to a delayed nonmatching to position procedure and were challenged with increasing doses of scopolamine hydrobromide (a central and peripheral muscarinic receptor blocker) and scopolamine methyl bromide (which does not pass the blood-brain barrier). Response accuracy decreased in both sexes as the delay interval duration increased. Behavioral differences between saline-treated males and females were not observed. Response accuracy decreased dose-dependently after subjects were injected with scopolamine hydrobromide. Response accuracy also decreased after treatment with scopolamine methyl bromide, but to a smaller extent. Males showed less accurate responding after treatment with either drug than females. These results provide behavioral evidence for the hypothesis that cholinergic functioning may differ between the sexes.

Animals↗
PubMed2002

Neuropsychology of bipolar disorder: a review.

BACKGROUND: Bipolar disorder (BD) may be associated with significant and persistent cognitive impairment. The aim of this study was to describe the profile of cognitive deficits in BD at different phases of the illness and determine whether it is different from that of schizophrenia and unipolar (UP) depression. METHODS: A systematic review of the computerised literature of neuropsychological studies of BD published between 1980 and 2000. RESULTS: General intellectual function: this was largely preserved in BD. Impairments when present were limited to acute episodes and to performance scores. Attention: attentional abnormalities were seen in symptomatic BD patients and persisted in remission in measures of sustained attention and inhibitory control. Memory: verbal memory was impaired even in euthymic patients while visuo-spatial memory deficits were variable depending on the tasks used. Executive function: all aspects of executive function (planning, abstract concept formation, set shifting) were impaired in symptomatic BD patients. Performance on executive function tests was sensitive to the presence of even residual symptoms but it may be normal in fully recovered patients with uncomplicated BD. Comparison to other patient groups: no major differences in cognitive profile between BD and UP depression were found. Remitted BD patients out-performed stable schizophrenics on most cognitive measures but this advantage disappeared when they were acutely symptomatic. CONCLUSIONS: Symptomatic BD patients have widespread cognitive abnormalities. Trait related deficits appear to be present in verbal memory and sustained attention. Executive function and visual memory may be also affected at least in some recovered BD patients.

Bipolar Disorder↗
PubMed1985

A psychopharmacological perspective of cognitive functions. II. Specific pharmacologic agents.

In this article we review the effects of specific drugs or neurotransmitter systems on cognitive functions. While much of what we know about drugs' effects on memory is derived from animal experiments, this review focuses on studies relevant to human clinical conditions. We conclude with a speculative analysis or taxonomy of the pharmacology of memory which broadly highlights the utility of viewing memory as being comprised of several differentiated processes.

Adrenal Cortex Hormones↗
PubMed1988

Requirement of Ia-positive nylon wool adherent cells for activation of cytotoxic T-lymphocytes specific to melanocyte-associated antigens in patients with Vogt-Koyanage-Harada's disease.

Involvement of Ia-positive nylon wool adherent cells (AC) for the expression of cytotoxic T-lymphocyte (CTL) activity specific to melanocyte-associated antigens (MAA) was studied. Although unseparated peripheral blood lymphocytes (PBL) from several patients with Vogt-Koyanagi-Harada's (VKH) disease showed significant cytotoxic activity against SK-MEL-28 (P-36) human melanoma cells which carried cross-reactive surface antigens with normal melanocytes, the cytotoxic activity of nylon wool column passed nonadherent cells (NAC) against the same target cells markedly decreased in the absence of Ia-positive nylon wool AC. The reduced cytotoxic activity of the NAC was reconstituted not only by the addition of Ia-positive AC from the same VKH patient, but also by the addition of allogeneic IA-positive AC mismatched with human leukocyte antigen (HLA) complex-DR region haplotype. Moreover, the cytotoxic activity of nylon wool NAC was augmented by the addition of interleukins instead of DR-positive AC. The data indicate that the primed CTL in patients with VKH would be stimulated nonspecifically by factors from Ia-positive cells, presumably to differentiate the precursor CTL (CTL in memory state) into mature CTL (effector cells).

Adult↗
PubMed2002

The humour effect: differential processing and privileged retrieval.

The effects of humour on memory and heart rate were explored as a function of experimental design. In within-subject manipulations, original humorous cartoons were better remembered than the literal translations and weird cartoons, whereas literal and weird cartoons were equally well remembered. Good recall of humorous cartoons occurred at the expense of recall of non-humorous cartoons. Secondary heart-rate deceleration was larger in response to original cartoons than to literal and weird cartoons. Neither the memory nor the heart-rate effects were found in between-subjects comparisons. The results were consistent with differential processing resulting from within-list contrasts. However, retrieval processes also favoured good recall of humorous material.

Heart Rate↗
PubMed1988

Limiting-dilution analysis of human CTL differentiation. Requirement for a lymphokine-mediated differentiation signal.

The induction of human influenza virus-specific memory cytotoxic T lymphocytes (CTL) from CTL precursors (CTLp) was investigated using limiting-dilution cultures and cell lines. Differentiation of maximal numbers of CTLp in limiting-dilution cultures required at least three signals: antigen stimulation, interleukin-2 (IL-2), and a differentiation factor distinct from IL-2. Antigen-specific CTLp proliferated in response to antigen stimulation and recombinant DNA-derived IL-2, but often failed to acquire cytolytic activity unless conditioned medium (CM) from mitogen-stimulated peripheral blood mononuclear cell (PBMC) cultures was added to the cultures. Temporal analysis of the requirement for CM indicated that it was providing a late signal for CTLp differentiation. This analysis was confirmed by developing CTLp cell lines, which were found to proliferate in response to IL-2 and antigen but not to exhibit influenza virus-specific cytotoxicity until CM was added.

Cell Differentiation↗
PubMed2006

Molecular nodes in memory processing: insights from Aplysia.

Recent research in a variety of systems indicates that memory formation can involve the activation of a wide range of molecular cascades. In assessing this recent work it is clear that no single cascade is uniquely important for all forms of memory, nor is a single form of memory uniquely dependent on a single cascade. Rather, it appears that molecular networks are differentially engaged in the induction of various forms of memory. Despite this highly interactive array of possible cascades, specific 'molecular nodes' have emerged as critical regulatory points in memory formation. Functionally, these nodes can operate in two sequential steps, beginning with a convergence of inputs which coordinately influence the activation state of the node, in which the nature of stimulation determines the dynamics of nodal activity, followed by a divergence of substrate selection, in which the node serves as a gateway that activates specific downstream effectors. Finally, specific nodes can be differentially engaged (i.e. have different 'weights') depending upon the nature and pattern of the activating stimulus. The marine mollusk Aplysia has proven useful for a molecular analysis of memory formation. We will use this system to highlight some of the molecular strategies employed by the nervous system in the formation of memory for sensitization, and we will focus on extracellular signal-related kinase as a candidate node integral to these processes.

Animals↗
PubMed1999

T cell memory against colon carcinoma is long-lived in the absence of antigen.

Eradication of established colon carcinoma metastases is a major goal for adjuvant immunotherapy of this disease. This was accomplished in a murine model by targeting IL-2 to the tumor microenvironment with a recombinant Ab-IL-2 fusion protein (huKS1/4-IL-2). The generation of a long-lived protective immunity was demonstrated by a 10- to 14-fold increase in CTL precursor (pCTL) frequency and induction of genes encoding Th1 cytokines, followed by the generation of tumor-specific CD8+ T effector cells, some of which differentiated into long-lived T memory cells. The frequency of pCTL correlated with enhanced immune protection against tumor cell challenge, and long-lived T cell memory was maintained in syngeneic SCID mice in the absence of tumor Ag. Tumor cell challenge of these SCID mice, concomitant with a boost of two noncurative doses of huKS1/4-IL-2 fusion protein, resulted in the generation of primed CD8+ T effector cells with concurrent release of Th1 cytokines. These events culminated in the complete rejection of the tumor cell challenge and prevention of pulmonary metastases. Taken together, the data suggest that T cell memory against colon carcinoma can be maintained in the absence of Ag.

Animals↗