scholarly journals p75NTR as a Molecular Memory Switch

2019 ◽  
Author(s):  
Shen Ning ◽  
Mehdi Jorfi
Keyword(s):  
Memory Consolidation ◽  
Sleep Disturbances ◽  
Biological Function ◽  
Neurological Diseases ◽  
Molecular Memory ◽  
Sleep Research ◽  
Memory Traces ◽  
The Impact ◽  
Synaptic Circuitry

In recent years, many molecular and environmental factors have been studied to understand how synaptic plasticity is modulated. Sleep, as an evolutionary conserved biological function, has shown to be a critical player for the consolidation and filtering of synaptic circuitry underlying memory traces. Although sleep disturbances do not alter normal memory consolidation, they may reflect fundamental circuit malfunctions that can play a significant role in exacerbating diseases, such as autism and Alzheimer’s disease. Very recently, scientists sought to answer part of this enigma and they identified p75 neurotrophic receptor (p75NTR) as a critical player in mediating impairments in hippocampal-dependent associative plasticity upon sleep deprivation. This paper will review the role of the p75NTR, critically discuss the impact and implications of this research as the bridge for sleep research and neurological diseases.

scholarly journals Role and Therapeutic Potential of Melatonin in the Central Nervous System and Cancers

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1567
Author(s):  
Sangiliyandi Gurunathan ◽  
Min-Hee Kang ◽  
Jin-Hoi Kim
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Circadian Rhythms ◽  
Pineal Gland ◽  
Therapeutic Potential ◽  
Neurological Diseases ◽  
Dark Phase ◽  
Anti Inflammatory ◽  
The Impact

Melatonin (MLT) is a powerful chronobiotic hormone that controls a multitude of circadian rhythms at several levels and, in recent times, has garnered considerable attention both from academia and industry. In several studies, MLT has been discussed as a potent neuroprotectant, anti-apoptotic, anti-inflammatory, and antioxidative agent with no serious undesired side effects. These characteristics raise hopes that it could be used in humans for central nervous system (CNS)-related disorders. MLT is mainly secreted in the mammalian pineal gland during the dark phase, and it is associated with circadian rhythms. However, the production of MLT is not only restricted to the pineal gland; it also occurs in the retina, Harderian glands, gut, ovary, testes, bone marrow, and lens. Although most studies are limited to investigating the role of MLT in the CNS and related disorders, we explored a considerable amount of the existing literature. The objectives of this comprehensive review were to evaluate the impact of MLT on the CNS from the published literature, specifically to address the biological functions and potential mechanism of action of MLT in the CNS. We document the effectiveness of MLT in various animal models of brain injury and its curative effects in humans. Furthermore, this review discusses the synthesis, biology, function, and role of MLT in brain damage, and as a neuroprotective, antioxidative, anti-inflammatory, and anticancer agent through a collection of experimental evidence. Finally, it focuses on the effect of MLT on several neurological diseases, particularly CNS-related injuries.

Evidence on the New Drug Lumateperone (ITI-007) for Psychiatric and Neurological Disorders

2020 ◽  
Vol 19 (4) ◽  
pp. 243-247
Author(s):  
Marianna Mazza ◽  
Giuseppe Marano ◽  
Gianandrea Traversi ◽  
Gabriele Sani ◽  
Luigi Janiri
Keyword(s):  
Sleep Disturbances ◽  
Bipolar Depression ◽  
Neurological Diseases ◽  
D1 Receptors ◽  
Serotoninergic System ◽  
Binding Affinities ◽  
Favourable Safety ◽  
Favourable Safety Profile ◽  
Unique Mechanism

: Lumateperone (ITI-007) is a tosylate salt with binding affinities to receptors implicated in the therapeutic actions of antipsychotic medications, including the serotonin 5HT2A receptors, dopamine D2 and D1 receptors and the serotonin transporter. It has a unique mechanism of action because it simultaneously modulates serotonin, dopamine, and glutamate neurotransmission, implicated in serious mental illness. It can be considered a multi-target-directed ligand and a multifunctional modulator of serotoninergic system with possible precognitive, antipsychotic, antidepressant and anxiolytic properties. Lumateperone has been investigated as a novel agent for the treatment of schizophrenia, but it represents a new potential option for other psychiatric and neurological diseases, such as behavioural symptoms of dementia or Alzheimer’s disease, sleep disturbances, bipolar depression. Besides, it has demonstrated a favourable safety profile without significant extrapyramidal side effects, hyperprolactinemia or changes in cardiometabolic or endocrine factors versus placebo. Additional studies are warranted to confirm and examine the benefit of lumateperone and possible therapeutic targets. This paper is a comprehensive and thorough summary of the most important findings and potential future role of this particular compound in personalized treatments.

scholarly journals Osteoarthritis: Novel Molecular Mechanisms Increase Our Understanding of the Disease Pathology

2021 ◽  
Vol 10 (9) ◽  
pp. 1938
Author(s):  
Susanne Grässel ◽  
Frank Zaucke ◽  
Henning Madry
Keyword(s):  
Sleep Disturbances ◽  
Molecular Mechanisms ◽  
Structural Defects ◽  
Tissue Destruction ◽  
Therapeutic Approaches ◽  
Joint Tissue ◽  
Structural Deterioration ◽  
Exact Etiology ◽  
The Impact

Although osteoarthritis (OA) is the most common musculoskeletal condition that causes significant health and social problems worldwide, its exact etiology is still unclear. With an aging and increasingly obese population, OA is becoming even more prevalent than in previous decades. Up to 35% of the world’s population over 60 years of age suffers from symptomatic (painful, disabling) OA. The disease poses a tremendous economic burden on the health-care system and society for diagnosis, treatment, sick leave, rehabilitation, and early retirement. Most patients also experience sleep disturbances, reduced capability for exercising, lifting, and walking and are less capable of working, and maintaining an independent lifestyle. For patients, the major problem is disability, resulting from joint tissue destruction and pain. So far, there is no therapy available that effectively arrests structural deterioration of cartilage and bone or is able to successfully reverse any of the existing structural defects. Here, we elucidate novel concepts and hypotheses regarding disease progression and pathology, which are relevant for understanding underlying the molecular mechanisms as a prerequisite for future therapeutic approaches. Emphasis is placed on topographical modeling of the disease, the role of proteases and cytokines in OA, and the impact of the peripheral nervous system and its neuropeptides.

scholarly journals Memory consolidation is linked to spindle-mediated information processing during sleep

2017 ◽  
Author(s):  
S.A. Cairney ◽  
A. Guttesen ◽  
N. El Marj ◽  
B.P. Staresina
Keyword(s):  
Information Processing ◽  
Memory Consolidation ◽  
Nrem Sleep ◽  
Associative Memories ◽  
Sensory Cues ◽  
Retrieval Performance ◽  
Memory Traces ◽  
Up States ◽  
Eeg Pattern

AbstractHow are brief encounters transformed into lasting memories? Previous research has established the role of non-rapid eye movement (NREM) sleep, along with its electrophysiological signatures of slow oscillations (SOs) and spindles, for memory consolidation. More recently, experimental manipulations have demonstrated that NREM sleep provides a window of opportunity to selectively strengthen particular memory traces via the delivery of sensory cues. It has remained unclear, however, whether experimental memory cueing triggers the brain’s endogenous consolidation mechanisms (linked to SOs and/or spindles) and whether those mechanisms in turn mediate effective processing of the cue information. Here we devised a novel paradigm in which associative memories (adjective-object and adjective-scene pairs) were selectively cued during a post-learning nap, successfully stabilising next-day retention relative to non-cued memories. First, we found that compared to novel control adjectives, memory cues were accompanied by an increase in fast spindles coupled to SO up states. Critically, EEG pattern decodability of the associated memory category (object vs. scene) was temporally linked to cue-induced spindles and predicted next-day retrieval performance across participants. These results provide highly controlled empirical evidence for an information processing role of sleep spindles in service of memory consolidation.

scholarly journals Stimulation augments spike sequence replay and memory consolidation during slow-wave sleep

2019 ◽  
Author(s):  
Yina Wei ◽  
Giri P Krishnan ◽  
Lisa Marshall ◽  
Thomas Martinetz ◽  
Maxim Bazhenov
Keyword(s):  
Slow Wave ◽  
Memory Consolidation ◽  
Temporal Pattern ◽  
Slow Wave Sleep ◽  
Sensory Stimulation ◽  
Slow Waves ◽  
Memory Traces ◽  
Spatio Temporal ◽  
Synaptic Level

AbstractNewly acquired memory traces are spontaneously reactivated during slow-wave sleep (SWS), leading to the consolidation of recent memories. Empirical studies found that sensory stimulation during SWS selectively enhances memory consolidation and the effect depends on the phase of stimulation. In this new study, we aimed to understand the mechanisms behind the role of sensory stimulation on memory consolidation using computational models implementing effects of neuromodulators to simulate transitions between awake and SWS sleep, and synaptic plasticity to allow the change of synaptic connections due to the training in awake or replay during sleep. We found that when closed-loop stimulation was applied during the Down states (900-2700) of sleep slow oscillation, particularly right before transition from Down to Up state, it significantly affected the spatio-temporal pattern of the slow-waves and maximized memory replay. In contrast, when the stimulation was presented during the Up states (2700-3600 and 00-900), it did not have a significant impact on the slow-waves or memory performance after sleep. For multiple memories trained in awake, presenting stimulation cues associated with specific memory trace could selectively augment replay and enhance consolidation of that memory and interfere with consolidation of the others (particularly weak) memories. Our study proposes a synaptic level mechanism of how memory consolidation is affected by sensory stimulation during sleep.Significance statementStimulation, such as training-associated cues or auditory stimulation, during sleep can augment consolidation of the newly encoded memories. In this study, we used a computational model of the thalamocortical system to describe the mechanisms behind the role of stimulation in memory consolidation during slow-wave sleep. Our study suggested that stimulation preferentially strengthens the memory traces when delivered at specific phase of slow oscillations just before Down to Up state transition when it makes the largest impact on the spatio-temporal pattern of sleep slow waves. In the presence of multiple memories, presenting sensory cues during sleep could selectively strengthen selected memories. Our study proposes a synaptic level mechanism of how memory consolidation is affected by sensory stimulation during sleep.

The Impact of Phytosterols on the Healthy and Diseased Brain

2019 ◽  
Vol 26 (37) ◽  
pp. 6750-6765 ◽  
Author(s):  
Tess Dierckx ◽  
Jeroen F.J. Bogie ◽  
Jerome J.A. Hendriks
Keyword(s):  
Cholesterol Metabolism ◽  
Neurological Diseases ◽  
Physiological Role ◽  
Cholesterol Homeostasis ◽  
Brain Functioning ◽  
The Central Nervous System ◽  
And Function ◽  
The Impact ◽  
The Brain

The central nervous system (CNS) is the most cholesterol-rich organ in mammals. Cholesterol homeostasis is essential for proper brain functioning and dysregulation of cholesterol metabolism can lead to neurological problems. Multiple sclerosis (MS) and Alzheimer’s disease (AD) are examples of neurological diseases that are characterized by a disturbed cholesterol metabolism. Phytosterols (PS) are plant-derived components that structurally and functionally resemble cholesterol. PS are known for their cholesterol-lowering properties. Due to their ability to reach the brain, researchers have started to investigate the physiological role of PS in the CNS. In this review, the metabolism and function of PS in the diseased and healthy CNS are discussed.

scholarly journals The effect of zolpidem on memory consolidation over a night of sleep

SLEEP ◽  
2020 ◽  
Vol 43 (11) ◽  
Author(s):  
Jing Zhang ◽  
Ben Yetton ◽  
Lauren N Whitehurst ◽  
Mohsen Naji ◽  
Sara C Mednick
Keyword(s):  
Eye Movement ◽  
Memory Consolidation ◽  
Memory Performance ◽  
Causal Role ◽  
Sleep Spindles ◽  
Double Blind ◽  
Episodic Memories ◽  
The Impact

Abstract Study Objectives: Nonrapid eye movement sleep boosts hippocampus-dependent, long-term memory formation more so than wake. Studies have pointed to several electrophysiological events that likely play a role in this process, including thalamocortical sleep spindles (12–15 Hz). However, interventional studies that directly probe the causal role of spindles in consolidation are scarce. Previous studies have used zolpidem, a GABA-A agonist, to increase sleep spindles during a daytime nap and promote hippocampal-dependent episodic memory. The current study investigated the effect of zolpidem on nighttime sleep and overnight improvement of episodic memories. Methods: We used a double-blind, placebo-controlled within-subject design to test the a priori hypothesis that zolpidem would lead to increased memory performance on a word-paired associates task by boosting spindle activity. We also explored the impact of zolpidem across a range of other spectral sleep features, including slow oscillations (0–1 Hz), delta (1–4 Hz), theta (4–8 Hz), sigma (12–15 Hz), as well as spindle–SO coupling. Results: We showed greater memory improvement after a night of sleep with zolpidem, compared to placebo, replicating a prior nap study. Additionally, zolpidem increased sigma power, decreased theta and delta power, and altered the phase angle of spindle–SO coupling, compared to placebo. Spindle density, theta power, and spindle–SO coupling were associated with next-day memory performance. Conclusions: These results are consistent with the hypothesis that sleep, specifically the timing and amount of sleep spindles, plays a causal role in the long-term formation of episodic memories. Furthermore, our results emphasize the role of nonrapid eye movement theta activity in human memory consolidation.

Intergroup Threat and Outgroup Attitudes

2013 ◽  
Vol 44 (5) ◽  
pp. 311-319 ◽  
Author(s):  
Marco Brambilla ◽  
David A. Butz
Keyword(s):  
Gay Men ◽  
Social Group ◽  
Welfare Recipients ◽  
Intergroup Attitudes ◽  
Social Policies ◽  
Intergroup Threat ◽  
Economic Threat ◽  
The Impact ◽  
General Climate

Two studies examined the impact of macrolevel symbolic threat on intergroup attitudes. In Study 1 (N = 71), participants exposed to a macrosymbolic threat (vs. nonsymbolic threat and neutral topic) reported less support toward social policies concerning gay men, an outgroup whose stereotypes implies a threat to values, but not toward welfare recipients, a social group whose stereotypes do not imply a threat to values. Study 2 (N = 78) showed that, whereas macrolevel symbolic threat led to less favorable attitudes toward gay men, macroeconomic threat led to less favorable attitudes toward Asians, an outgroup whose stereotypes imply an economic threat. These findings are discussed in terms of their implications for understanding the role of a general climate of threat in shaping intergroup attitudes.

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