Vascular memory: can we broaden the concept of the metabolic memory?

ABSTRACT: Based on the results of recent randomized, controlled clinical trials and analyses of their follow-up periods the concept of metabolic memory cannot be restricted to antihyperglycaemic treatment only, rather it can be extended to lipid-lowering and antihypertensive treatment and even life-style modification. This broadened concept can be designated as vascular memory. According to this new concept, not only immediate and short-term but long-term effects of the metabolic and cardiovascular risk milieu are of great importance. Consequently, early and intensive lifestyle interventions, treatment of hyperglycaemia, lipid abnormalities and hypertension can result in beneficial effects on cardiovascular outcomes even in the long run. On the contrary, failing in target-oriented treatment from early detection of abnormalities can be associated with life-threatening cardiovascular events subsequently. Additional experimental studies are needed to characterize the exact pathomechanism of vascular memory and further clinical trials are also essential to explore its real clinical significance.     

Recognition memory: what are the roles of the perirhinal cortex and hippocampus?

The hallmark of medial temporal lobe amnesia is a loss of episodic memory such that patients fail to remember new events that are set in an autobiographical context (an episode). A further symptom is a loss of recognition memory. The relationship between these two features has recently become contentious. Here, we focus on the central issue in this dispute--the relative contributions of the hippocampus and the perirhinal cortex to recognition memory. A resolution is vital not only for uncovering the neural substrates of these key aspects of memory, but also for understanding the processes disrupted in medial temporal lobe amnesia and the validity of animal models of this syndrome.     

Problems of learning and memory: one or multiple memory systems?

Learning, and hence memory, is ubiquitous not only throughout the animal kingdom, but apparently throughout many regions of the brain. Is all learning reducible to a single common form? Neuropsychological dissociations suggest that the mammalian brain possesses a number of different and potentially independent memory systems, with different mechanisms and anatomical dispositions, some of which are neurally widely dispersed and others of which are narrowly organized. Among the types considered are: (i) short-term memory; (ii) knowledge and skills; (iii) stable associative memory; (iv) event memory; and (v) priming. As double or multiple dissociations do not lead to logically inevitable conclusions, it has been argued that an alternative to multiple memory systems is variable modes of processing. But these, too, would be dissociable on the same lines of evidence. Dissociations, if strong and absolute, have strong pragmatic power when they are combined with evolutionary and neuroscientific evidence. Multiple memory systems may possibly share some common cellular mechanisms, but such mechanisms do not define the separate properties at the systems level.     

In vitro and in vivo comparisons of the effects of the fruiting body and mycelium of Antrodia camphorata against amyloid β-protein-induced neurotoxicity and memory impairment

Antrodia camphorata is a particular and precious medicinal mushroom, and its fruiting body was found to provide more efficient protection from oxidative stress and inflammation than its mycelium because of its higher content of triterpenoids, total phenols, and so on. In the previous in vitro studies, the mycelium of A. camphorata is proven to provide strong neuroprotection in neuron cells and suggested to have the potential of protection against neurotoxicity of amyloid β-protein (Aβ) known as the risk factor toward Alzheimer's disease (AD) development. However, the in vivo study and the comparison study with the fruiting body have not yet been investigated. This study compared the effect of the fruiting body and mycelium of A. camphorata on alleviating the Aβ40-induced neurocytotoxicity in the in vitro Aβ-damaged neuron cell model (PC-12 cell treated with Aβ40) and memory impairment in the in vivo AD animal model induced with a continuous brain infusion of Aβ40. In the results of in vitro and in vivo studies, the fruiting body possessed stronger anti-oxidative and anti-inflammatory abilities for inhibiting neurocytotoxicity in Aβ40-treated PC-12 cells and Aβ40 accumulation in Aβ40-infused brain than mycelium. Moreover, hyperphosphorylated tau (p-tau) protein expression, known as an important AD risk factor, was suppressed by the treatment of fruiting body rather than that of mycelium in the in vitro and in vivo studies. These comparisons supported the reasons why the fruiting body resulted in a more significant improvement effect on working memory ability than mycelium in the AD rats.     

Rarity,ecological memory,rate of floral change in phytoplankton—and the mystery of the Red Cock

In this article, we attempt to estimate the contemporary phytoplankton species pool of a particular lake, by assessing the rate of floral change over a period of 15 years. Phytoplankton time series data from Lake Stechlin, an oligo-mesotrophic lake in the Baltic Lake District (Germany) were used. Of the 254 algal species recorded during the 15-year of studies with roughly biweekly sampling, 212 species were planktonic. In the individual plankton years, the recorded total number of species changed between 97 and 122, of which the number of dominants (>1% contribution to the annual average of total biomass) was only 10–19. The 15-year cumulative number of species exhibited an almost linear increase after an initial saturation phase. This increase was attributed to two reasons: increase of sample size and immigration of species new to the flora. Based on a probabilistic model developed in this study, we estimated the number of co-existing planktonic species of the lake as some 180, and the rate of floral change as 1–2 species per year. Of these co-existing species, only few maintain the matter–energy processing ecosystem functions in any particular plankton year. Selection of these dominants is probably driven by mesoclimatic cycles, coupled with human-induced forcing, like eutrophication. All others are hiding as an ecological memory, in the sense of the capacity or experiences of past states to influence present or future responses of the community. Data analyses suggest that selection of the ‘memory species’ that show temporary abundance increases over shorter (several years) periods are largely dependent upon the dominants. These results show that interspecific interactions and the particular autecological features of the dominants, together with their effects on the whole ecosystem, act as a major organizing force. Some phytoplankton species, like Planktothrix rubescens, are efficient ecosystem engineers with cascading effects of both a top-down and bottom-up nature. Historical scientific data on Planktothrix blooms in Lake Stechlin suggest cyclic patterns in long-term development of phytoplankton which, as the legend of the Red Cock suggests, dates back much further than scientific archives.     

Can the theory of critical distances predict the failure of shape memory alloys?

Components made from shape memory alloys (SMAs) such as nitinol often fail from stress concentrations and defects such as notches and cracks. It is shown here for the first time that these failures can be predicted using the theory of critical distances (TCDs), a method which has previously been used to study fracture and fatigue in other materials. The TCD uses the stress at a certain distance ahead of the notch to predict the failure of the material due to the stress concentration. The critical distance is believed to be a material property which is related to the microstructure of the material. The TCD is simply applied to a linear model of the material without the need to model the complication of its non-linear behaviour. The non-linear behaviour of the material at fracture is represented in the critical stress. The effect of notches and short cracks on the fracture of SMA NiTi was studied by analysing experimental data from the literature. Using a finite element model with elastic material behaviour, it is shown that the TCD can predict the effect of crack length and notch geometry on the critical stress and stress intensity for fracture, with prediction errors of less than 5%. The value of the critical distance obtained for this material was L?=?90?μm; this may be related to its grain size. The effects of short cracks on stress intensity were studied. It was shown that the same value of the critical distance (L?=?90?μm) could estimate the experimental data for both notches and short cracks.     

Regulation of naïve and memory T-cell homeostasis

Recent work has confirmed the existence of homeostatic mechanisms that regulate the overall size and composition of the mature T-cell pool. Homeostatic mechanisms not only control total T-cell numbers but appear to act differently on na?ve vs. memory cells. The roles of self-MHC/peptide ligands and certain cytokines in T-cell homeostasis are discussed.     

Roles of α- and β-estrogen receptors in mouse social recognition memory: effects of gender and the estrous cycle

Establishing clear effects of gender and natural hormonal changes during female ovarian cycles on cognitive function has often proved difficult. Here we have investigated such effects on the formation and long-term (24 h) maintenance of social recognition memory in mice together with the respective involvement of α- and β-estrogen receptors using α- and β-estrogen receptor knockout mice and wildtype controls. Results in wildtype animals showed that while females successfully formed a memory in the context of a habituation/dishabituation paradigm at all stages of their ovarian cycle, only when learning occurred during proestrus (when estrogen levels are highest) was it retained after 24 h. In α-receptor knockout mice (which showed no ovarian cycles) both formation and maintenance of this social recognition memory were impaired, whereas β-receptor knockouts showed no significant deficits and exhibited the same proestrus-dependent retention of memory at 24 h. To investigate possible sex differences, male α- and β-estrogen receptor knockout mice were also tested and showed similar effects to females excepting that α-receptor knockouts had normal memory formation and only exhibited a 24 h retention deficit. This indicates a greater dependence in females on α-receptor expression for memory formation in this task. Since non-specific motivational and attentional aspects of the task were unaffected, our findings suggest a general α-receptor dependent facilitation of memory formation by estrogen as well as an enhanced long-term retention during proestrus. Results are discussed in terms of the differential roles of the two estrogen receptors, the neural substrates involved and putative interactions with oxytocin.     

Tip off the HAT– Epigenetic control of learning and memory by Drosophila Tip60

Disruption of epigenetic gene control mechanisms involving histone acetylation in the brain causes cognitive impairment, a debilitating hallmark of most neurodegenerative disorders. Histone acetylation regulates cognitive gene expression via chromatin packaging control in neurons. Unfortunately, the histone acetyltransferases (HATs) that generate such neural epigenetic signatures and their mechanisms of action remain unclear. Our recent findings provide insight into this question by demonstrating that Tip60 HAT action is critical for morphology and function of the mushroom body (MB), the learning and memory center in the Drosophila brain. We show that Tip60 is robustly produced in MB Kenyon cells and extending axonal lobes and that targeted MB Tip60 HAT loss results in axonal outgrowth disruption. Functional consequences of loss and gain of Tip60 HAT levels in the MB are evidenced by defects in memory. Tip60 ChIP-Seq analysis reveals enrichment for genes that function in cognitive processes and accordingly, key genes representing these pathways are misregulated in the Tip60 HAT mutant fly brain. Remarkably, increasing levels of Tip60 in the MB rescues learning and memory deficits resulting from Alzheimer's disease associated amyloid precursor protein (APP) induced neurodegeneration. Our studies highlight the potential of HAT activators as a therapeutic option for cognitive disorders.     

Tip off the HAT– Epigenetic control of learning and memory by Drosophila Tip60

Disruption of epigenetic gene control mechanisms involving histone acetylation in the brain causes cognitive impairment, a debilitating hallmark of most neurodegenerative disorders. Histone acetylation regulates cognitive gene expression via chromatin packaging control in neurons. Unfortunately, the histone acetyltransferases (HATs) that generate such neural epigenetic signatures and their mechanisms of action remain unclear. Our recent findings provide insight into this question by demonstrating that Tip60 HAT action is critical for morphology and function of the mushroom body (MB), the learning and memory center in the Drosophila brain. We show that Tip60 is robustly produced in MB Kenyon cells and extending axonal lobes and that targeted MB Tip60 HAT loss results in axonal outgrowth disruption. Functional consequences of loss and gain of Tip60 HAT levels in the MB are evidenced by defects in memory. Tip60 ChIP-Seq analysis reveals enrichment for genes that function in cognitive processes and accordingly, key genes representing these pathways are misregulated in the Tip60 HAT mutant fly brain. Remarkably, increasing levels of Tip60 in the MB rescues learning and memory deficits resulting from Alzheimer''s disease associated amyloid precursor protein (APP) induced neurodegeneration. Our studies highlight the potential of HAT activators as a therapeutic option for cognitive disorders.     

The End of the Beginning? Mining,sacred geographies,memory and performance in Lihir

This article explores the critical ways in which the relationship between landscape and memory is mediated by performance—through song, dance, ritual and the movements of the living and the dead. In the Lihir group of islands, in Papua New Guinea, these acts of memorialisation are rehearsed on a remarkable stage, an involuted cosmography or sacred geography in which the cosmological point of origin, the sacred rock of Ailaya, is also the ultimate destination for all human and spirit forms. Spirit beings are held to have emerged from the Ailaya, spreading across the island group, their tracks charting the links amongst distant clan members and the networks of alliance between trading partners. It is to the Ailaya that the spirits of deceased Lihirians must return, following preparatory mortuary rites and sung along a route that recalls the spirit connections. This teleological process is mapped through an account of the performance of relationships between people and land, to which an additional layer of complexity is added by the presence of a giant gold mine, in which the Ailaya is again the central feature.     

Development of the brain’s organization of working memory in young schoolchildren

In 7–8 and 9–10-years old children, we studied event-related potentials (ERPs) during paired comparison of non-verbalizable visuospatial stimuli presented at an interval of 1.5–1.8 s. Age-related differences were found in the involvement of various cortical areas in the formation and retention of a short-term memory trace of the reference stimulus and during comparison of the short-term trace with the test stimulus presented. In both age groups, working memory was associated with an elevation of the amplitude of the sensory-specific N1 component in the visual cortical areas. Age-related differences in the processing of sensory-specific characteristics of a stimulus were the greatest in the ERPs to the test stimulus: at the age of 9–10, the N1 component amplitude was significantly increased in all caudal leads and, in the occipital and inferior temporal leads, this component was preceded by P1 component. At this age, we observed the early involvement of the inferior frontal cortex, which was not observed at the age of seven. The increase in positivity over that area was observed in the interval of 100–200 ms. Substantial differences between age groups were found in the late ERP component corresponding to cognitive processes. At the age of 7–8, the presentation of both the reference and test stimuli causes the increase in the amplitude of the slow positive complex (SPC) in the caudal liads with the maximum enhancement found in the interval of 300–800 ms in the parietal leads. At the age of 9–10, the SPC increase, much like in adults, was observed in ERP to the test stimulus only. At this age, adult-like specific changes in the late phases of ERPs were observed in the fronto-central regions at the different stages of working memory. They are the increases in the negative N400 wave in the ERP to the reference stimulus and the SPC to the test stimulus. These data show that, at the age of 9–10, the functional organization of working memory of the adult type is formed; however, the extent to which the frontal cortex, and its dorsal regions in particular, is involved into working memory processes does not meet yet a definitive level.     

The effects of acute treatment with Δ9-THC on exploratory behaviour and memory in the rat

The aim of the present study was to evaluate the effects of delta9-tetrahydrocannabinol (delta9-THC) on exploratory behaviour and memory, independent of its locomotor suppressive effects. Dopamine (DA) and noradrenaline (NA) contents were determined in the areas of the brain directly related to such behaviours (hippocampus, striatum and amygdala). An acute dose of delta9-THC led to a decrease in exploratory parameters and motor activity during the holeboard test. The radial arm maze was used to evaluate the effects of this cannabinoid substance on memory. Animals treated with delta9-THC committed more errors in the maze test compared to control, particularly when the retention process was put to test. Furthermore, treatment with delta9-THC led to reduced NA contents in the hippocampus and increased DA contents in the amygdala, without changes in the striatum.     

Is cholinergic activity of the caudate nucleus involved in memory?

A review was made of experiments dealing with the involvement of cholinergic activity of the caudate nucleus in memory processes. Injections of acetylcholine-receptor blockers or of neurotoxins against cholinergic interneurons into the striatum produce marked impairments in acquisition and retention of instrumental tasks while injections of acetylcholine or choline into the caudate produce the opposite effect. However, after a period of overtraining cholinergic blockade or interference with neural activity of the caudate does not produce significant deficits in retention. It is concluded that striatal cholinergic activity is critically involved in memory of recent events and that long-term memory is mediated by different neurochemical systems outside the caudate nucleus.     

Uneven distributions of naïve and memory T cells in the CD4 and CD8 T-cell populations derived from a single stem cell in an atomic bomb survivor: implications for the origins of the memory T-cell pools in adulthood

The processes that lead to the establishment and maintenance of memory T-cell pools in humans are not well understood. In this study, we examined the emergence of na?ve and memory T cells in an adult male who was exposed to an atomic bomb radiation dose of approximately 2 Gy in 1945 at the age of 17. The analysis presented here was made possible by our earlier observation that this particular individual carries a hematopoietic stem cell mutation at the hypoxanthine phosphoribosyltransferase (HPRT) locus that is almost certainly a result of his exposure to A-bomb radiation. Our key finding is that we detected a very much higher HPRT mutant frequency in the naive (CD45RA(+)) cell component of this individual's CD4 and CD8 T-cell populations than in the memory (CD45RA(-)) cell component of his CD4 and CD8 T-cell populations. This stands in marked contrast to our finding that HPRT mutant frequencies are fairly similar in the na?ve CD45RA(+) and memory CD45RA(-) components of the CD4 and CD8 T-cell populations of three unexposed individuals examined concurrently. In addition we found that the HPRT mutant frequencies were about 30-fold higher in the na?ve (CD45RA(+)) CD4 T cells of the exposed individual than in his memory (CD45RA(-)) cell populations, but that the effect was a little less striking in his CD8 cell populations, where the HPRT mutant frequencies were only about 15-fold higher in his na?ve T-cell pools than in his memory T-cell pools. We further found that 100% of the HPRT mutant cells in both his CD4 and CD8 na?ve cell subsets appeared to have originated from repeated divisions of the initial HPRT mutant stem cell, whereas only 4 of 24 and 5 of 6 mutant cells in his CD4 and CD8 memory cell subsets appeared to have originated from that same stem cell. The most straightforward conclusion may be that the great majority of the T cells produced by this individual since he was 17 years old have remained as na?ve-type T cells, rather than having become memory-type T cells. Thus the T cells that have been produced from the hematopoietic stem cells of this particular A-bomb-exposed individual seldom seem to enter and/or to remain in the memory T-cell pool for long periods. We speculate that this constraint on entry into memory T-cell pools may also apply to unirradiated individuals, but in the absence of genetic markers to assist us in obtaining evidential support, we must await clarifying information from radically different experimental approaches.