Neuroscience
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The contribution of amyloid-β (Aβ) soluble forms to Alzheimer's Disease (AD) is undergoing revision and the characterization of monomeric, oligomeric and protofibrillar Aβ forms used in vivo to model AD is a critical step to ensure data interpretation. Atomic force microscopy (AFM) was used to characterize the nanoscale morphology of different Aβ42 forms also used for cerebroventricular injection (cvi) in young (6mo) and aged (36mo) adult zebrafish behavioral and cognitive tests. On the AFM, monomeric solution deposited onto mica resulted mostly in thin filamentous structures and shorter monomeric agglomerates with heights around or below 1.5 nm, as expected for single Aβ42. ⋯ On the Open Tank used to test exploratory parameters, no differences were observed between injected animals and their age-matched controls, except for a reduced distance travelled by aged individuals that received the Aβ42 oligomeric form. Long-term memory (LTM) for the inhibitory avoidance task was not influenced by monomers cvi, whilst oligomeric and fibrillar Aβ42 hindered LTM formation in young and aged groups. Our findings support current views of deleterious effects of Aβ42 soluble forms on cognition and ensures that preparations were structurally unique and within expected morphologies and dimensions.
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Spaced training, which involves long inter-trial intervals, has positive effects on memories. One of the main attributes of long-term memories (LTM) is persistence. Here, to identify the process that promotes LTM persistence by spaced learning, we used the spatial object recognition (SOR) task in rats. ⋯ Our results suggest that the mechanism of memory expression, but not those of memory reinforcement or reconsolidation, is necessary to promote memory persistence after retraining. The molecular mechanisms involve ERKs1/2 activity to set the SOR learning tag, and the availability of GluA2-containing AMPA receptor. In conclusion, both the synthesis of PRPs and the setting of learning tags are key processes triggered by retraining that allow SOR memory persistence.
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Microglia are unique cells in the central nervous system (CNS), being considered a sub-type of CNS macrophage. These cells monitor nearby micro-regions, having roles that far exceed immunological and scavengering functions, being fundamental for developing, protecting and maintaining the integrity of grey and white matter. Microglia might become dysfunctional, causing abnormal CNS functioning early or late in the life of patients, leading to neurologic or psychiatric disorders and premature death in some patients. ⋯ Alzheimer Disease is the prototype of the neurodegenerative disorders associated with these TREM2 variants, named here the Microgliopathies Type II. Here, we review clinical, pathological and some molecular aspects of human diseases associated with primary microglia dysfunctions and briefly comment some possible therapeutic approaches to theses microgliopathies. We hope that our review might update the interesting discussion about the impact of intrinsic microglia dysfunctions in the genesis of some pathologic processes of the CNS.
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The present paper provides a comprehensive review of latent extinction. In maze learning situations, latent extinction involves confining an animal to a previously reinforced goal location without food. When returned to the starting position after latent extinction, the animal typically shows a response decrement. ⋯ The hippocampus is critically involved in latent extinction, whereas other brain regions typically implicated in regular "response extinction" in the maze, such as the dorsolateral striatum, are not required for latent extinction. Similar to other kinds of learning, latent extinction requires NMDA receptor activity, suggesting the involvement of synaptic plasticity. Consistent with a multiple memory systems perspective, research on latent extinction supports the hypothesis that extinction learning is not a unitary process but rather there are different kinds of extinction learning mediated by distinct neural systems.
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A possible role for the brain β-endorphin system in memory modulation was proposed by Ivan Izquierdo more than 30 years ago. Along with pharmacologic evidence of the effects of morphine and naloxone administered immediately after training in avoidance tasks and with the demonstration of medial-basal hypothalamus β-endorphin release after novelty detection, it was hypothesized that an endogenous opioid state present in the labile period of consolidation will be part of the memory of the newly acquired information. ⋯ In this review some of the original papers in the subject are revisited. Recent studies on the memory beneficial effects of novelty, both in animal models and in humans, indicate this is line of investigation is worth of pursuing and demonstrate the importance of the seminal work of Ivan Izquierdo in the field of memory modulation.