scholarly journals Impairment in Long-Term Memory Formation and Learning-Dependent Synaptic Plasticity in Mice Lacking Glycogen Synthase in the Brain

2013 ◽  
Vol 33 (4) ◽  
pp. 550-556 ◽  
Author(s):  
Jordi Duran ◽  
Isabel Saez ◽  
Agnes Gruart ◽  
Joan J Guinovart ◽  
José M Delgado-García
Keyword(s):  
Cognitive Abilities ◽  
Glycogen Synthase ◽  
Long Term Potentiation ◽  
Normal Activity ◽  
Synaptic Strength ◽  
Long Term Memory ◽  
Brain Functions ◽  
The Brain

Glycogen is the only carbohydrate reserve of the brain, but its overall contribution to brain functions remains unclear. Although it has traditionally been considered as an emergency energetic reservoir, increasing evidence points to a role of glycogen in the normal activity of the brain. To address this long-standing question, we generated a brain-specific Glycogen Synthase knockout (GYS1Nestin-KO) mouse and studied the functional consequences of the lack of glycogen in the brain under alert behaving conditions. These animals showed a significant deficiency in the acquisition of an associative learning task and in the concomitant activity-dependent changes in hippocampal synaptic strength. Long-term potentiation (LTP) evoked in the hippocampal CA3-CA1 synapse was also decreased in behaving GYS1Nestin-KO mice. These results unequivocally show a key role of brain glycogen in the proper acquisition of new motor and cognitive abilities and in the underlying changes in synaptic strength.

scholarly journals GSK3α: An Important Paralog in Neurodegenerative Disorders and Cancer

Biomolecules ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1683
Author(s):  
Octavio Silva-García ◽  
Ricarda Cortés-Vieyra ◽  
Francisco N. Mendoza-Ambrosio ◽  
Guillermo Ramírez-Galicia ◽  
Víctor M. Baizabal-Aguirre
Keyword(s):  
Neurodegenerative Disorders ◽  
Glycogen Synthase ◽  
Similar Efficacy ◽  
Glycogen Synthase Kinase 3 ◽  
Brain Functions ◽  
Chemical Inhibitors ◽  
Simultaneous Inhibition ◽  
The Brain

The biological activity of the enzyme glycogen synthase kinase-3 (GSK3) is fulfilled by two paralogs named GSK3α and GSK3β, which possess both redundancy and specific functions. The upregulated activity of these proteins is linked to the development of disorders such as neurodegenerative disorders (ND) and cancer. Although various chemical inhibitors of these enzymes restore the brain functions in models of ND such as Alzheimer’s disease (AD), and reduce the proliferation and survival of cancer cells, the particular contribution of each paralog to these effects remains unclear as these molecules downregulate the activity of both paralogs with a similar efficacy. Moreover, given that GSK3 paralogs phosphorylate more than 100 substrates, the simultaneous inhibition of both enzymes has detrimental effects during long-term inhibition. Although the GSK3β kinase function has usually been taken as the global GSK3 activity, in the last few years, a growing interest in the study of GSK3α has emerged because several studies have recognized it as the main GSK3 paralog involved in a variety of diseases. This review summarizes the current biological evidence on the role of GSK3α in AD and various types of cancer. We also provide a discussion on some strategies that may lead to the design of the paralog-specific inhibition of GSK3α.

The role of PKMζ in the maintenance of long-term memory: a review

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Hamish Patel ◽  
Reza Zamani
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Long Term Potentiation ◽  
Global Memory ◽  
Long Term Memory ◽  
Compensatory Mechanism ◽  
Term Memory ◽  
Kinase C

Abstract Long-term memories are thought to be stored in neurones and synapses that undergo physical changes, such as long-term potentiation (LTP), and these changes can be maintained for long periods of time. A candidate enzyme for the maintenance of LTP is protein kinase M zeta (PKMζ), a constitutively active protein kinase C isoform that is elevated during LTP and long-term memory maintenance. This paper reviews the evidence and controversies surrounding the role of PKMζ in the maintenance of long-term memory. PKMζ maintains synaptic potentiation by preventing AMPA receptor endocytosis and promoting stabilisation of dendritic spine growth. Inhibition of PKMζ, with zeta-inhibitory peptide (ZIP), can reverse LTP and impair established long-term memories. However, a deficit of memory retrieval cannot be ruled out. Furthermore, ZIP, and in high enough doses the control peptide scrambled ZIP, was recently shown to be neurotoxic, which may explain some of the effects of ZIP on memory impairment. PKMζ knockout mice show normal learning and memory. However, this is likely due to compensation by protein-kinase C iota/lambda (PKCι/λ), which is normally responsible for induction of LTP. It is not clear how, or if, this compensatory mechanism is activated under normal conditions. Future research should utilise inducible PKMζ knockdown in adult rodents to investigate whether PKMζ maintains memory in specific parts of the brain, or if it represents a global memory maintenance molecule. These insights may inform future therapeutic targets for disorders of memory loss.

Neurotrophins and Proneurotrophins: Focus on Synaptic Activity and Plasticity in the Brain

2017 ◽  
Vol 23 (6) ◽  
pp. 587-604 ◽  
Author(s):  
Julien Gibon ◽  
Philip A. Barker
Keyword(s):  
Long Term Potentiation ◽  
Synaptic Activity ◽  
Cellular Processes ◽  
Term Potentiation ◽  
Neurotrophin 3 ◽  
New Findings ◽  
The Central Nervous System ◽  
The Brain

Neurotrophins have been intensively studied and have multiple roles in the brain. Neurotrophins are first synthetized as proneurotrophins and then cleaved intracellularly and extracellularly. Increasing evidences demonstrate that proneurotrophins and mature neurotrophins exerts opposing role in the central nervous system. In the present review, we explore the role of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT3), and neurotrophin 4 (NT4) and their respective proform in cellular processes related to learning and memory. We focused on their roles in synaptic activity and plasticity in the brain with an emphasis on long-term potentiation, long-term depression, and basal synaptic transmission in the hippocampus and the temporal lobe area. We also discuss new findings on the role of the Val66Met polymorphism on the BDNF propeptide on synaptic activity.

scholarly journals Neuro-Transistor Based on UV-Treated Charge Trapping in MoTe2 for Artificial Synaptic Features

Nanomaterials ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 2326
Author(s):  
Shania Rehman ◽  
Muhammad Farooq Khan ◽  
Mehr Khalid Rahmani ◽  
Honggyun Kim ◽  
Harshada Patil ◽  
...  
Keyword(s):  
Field Effect Transistors ◽  
Charge Trapping ◽  
Long Term Potentiation ◽  
Spike Timing ◽  
Long Term Memory ◽  
Ambient Conditions ◽  
Time Constants ◽  
Brain Functions ◽  
Gate Pulse

The diversity of brain functions depend on the release of neurotransmitters in chemical synapses. The back gated three terminal field effect transistors (FETs) are auspicious candidates for the emulation of biological functions to recognize the proficient neuromorphic computing systems. In order to encourage the hysteresis loops, we treated the bottom side of MoTe2 flake with deep ultraviolet light in ambient conditions. Here, we modulate the short-term and long-term memory effects due to the trapping and de-trapping of electron events in few layers of a MoTe2 transistor. However, MoTe2 FETs are investigated to reveal the time constants of electron trapping/de-trapping while applying the gate-voltage pulses. Our devices exploit the hysteresis effect in the transfer curves of MoTe2 FETs to explore the excitatory/inhibitory post-synaptic currents (EPSC/IPSC), long-term potentiation (LTP), long-term depression (LTD), spike timing/amplitude-dependent plasticity (STDP/SADP), and paired pulse facilitation (PPF). Further, the time constants for potentiation and depression is found to be 0.6 and 0.9 s, respectively which seems plausible for biological synapses. In addition, the change of synaptic weight in MoTe2 conductance is found to be 41% at negative gate pulse and 38% for positive gate pulse, respectively. Our findings can provide an essential role in the advancement of smart neuromorphic electronics.

scholarly journals The Role of Dietary Antioxidants in the Pathogenesis of Neurodegenerative Diseases and Their Impact on Cerebral Oxidoreductive Balance

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 435 ◽  
Author(s):  
Anna Winiarska-Mieczan ◽  
Ewa Baranowska-Wójcik ◽  
Małgorzata Kwiecień ◽  
Eugeniusz R. Grela ◽  
Dominik Szwajgier ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Negative Impact ◽  
Functional Disorders ◽  
Brain Functions ◽  
Diet Supplements ◽  
The Impact ◽  
The Brain ◽  
All Diseases

Neurodegenerative diseases are progressive diseases of the nervous system that lead to neuron loss or functional disorders. Neurodegenerative diseases require long-term, sometimes life-long pharmacological treatment, which increases the risk of adverse effects and a negative impact of pharmaceuticals on the patients’ general condition. One of the main problems related to the treatment of this type of condition is the limited ability to deliver drugs to the brain due to their poor solubility, low bioavailability, and the effects of the blood-brain barrier. Given the above, one of the main objectives of contemporary scientific research focuses on the prevention of neurodegenerative diseases. As disorders related to the competence of the antioxidative system are a marker in all diseases of this type, the primary prophylactics should entail the use of exogenous antioxidants, particularly ones that can be used over extended periods, regardless of the patient’s age, and that are easily available, e.g., as part of a diet or as diet supplements. The paper analyzes the significance of the oxidoreductive balance in the pathogenesis of neurodegenerative diseases. Based on information published globally in the last 10 years, an analysis is also provided with regard to the impact of exogenous antioxidants on brain functions with respect to the prevention of this type of diseases.

scholarly journals LARGE, an AMPA receptor interactor, plays a large role in long-term memory formation by driving homeostatic scaling-down

2017 ◽  
Author(s):  
Bo Am Seo ◽  
Taesup Cho ◽  
Daniel Z. Lee ◽  
Hwa Young Lee ◽  
Joong-Jae Lee ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Long Term Potentiation ◽  
Memory Formation ◽  
Fine Tuning ◽  
Functional Study ◽  
Long Term Memory ◽  
Term Memory ◽  
Scaling Down ◽  
The Brain

AbstractDynamic trafficking of AMPA-type glutamate receptor (AMPA-R) in neuronal cells is a key cellular mechanism for learning and memory in the brain, which is regulated by AMPA-R interacting proteins. LARGE, a protein associated with intellectual disability, was found to be a novel component of the AMPA-R protein complex in our proteomic study. Here, our functional study of LARGE showed that during homeostatic scaling-down, increased LARGE expression at the Golgi apparatus (Golgi) negatively controlled AMPA-R trafficking from the Golgi to the plasma membrane, leading to downregulated surface and synaptic AMPA-R targeting. In LARGE knockdown mice, long-term potentiation (LTP) was occluded by synaptic AMPA-R overloading, resulting in impaired long-term memory formation. These findings indicate that the fine-tuning of AMPA-R trafficking by LARGE at the Golgi is critical for memory stability in the brain. Our study thus provides novel insights into the pathophysiology of brain disorders associated with intellectual disability.

scholarly journals The role of microRNAs in learning and long-term memory

2020 ◽  
Vol 24 (8) ◽  
pp. 885-896
Author(s):  
L. N. Grinkevich
Keyword(s):  
Cognitive Processes ◽  
Regulation Of Gene Expression ◽  
Memory Formation ◽  
Learning Ability ◽  
Long Term Memory ◽  
Term Memory ◽  
Microrna Biogenesis ◽  
The Brain

The mechanisms of long-term memory formation and ways to improve it (in the case of its impairment) remain an extremely difficult problem yet to be solved. Over the recent years, much attention has been paid to microRNAs in this regard. MicroRNAs are unique endogenous non-coding RNAs about 22 nucleotides in length; each can regulate translation of hundreds of messenger RNA targets, thereby controlling entire gene networks. MicroRNAs are widely represented in the central nervous system. A large number of studies are currently being conducted to investigate the role of microRNAs in the brain functioning. A number of microRNAs have been shown to be involved in the process of synaptic plasticity, as well as in the long-term memory formation. Disruption of microRNA biogenesis leads to significant cognitive dysfunctions. Moreover, impaired microRNA biogenesis is one of the causes of the pathogenesis of mental disorders, neurodegenerative illnesses and senile dementia, which are often accompanied by deterioration in the learning ability and by memory impairment. Optimistic predictions are made that microRNAs can be used as targets for therapeutic treatment and for diagnosing the above pathologies. The importance of applications related to microRNAs significantly raises interest in studying their functions in the brain. Thus, this review is focused on the role of microRNAs in cognitive processes. It describes microRNA biogenesis and the role of miRNAs in the regulation of gene expression, as well as the latest achievements in studying the functional role of microRNAs in learning and in long-term memory formation, depending on the activation or inhibition of their expression. The review presents summarized data on the effect of impaired microRNA biogenesis on long-term memory formation, including those associated with sleep deprivation. In addition, analysis is provided of the current literature related to the prospects of improving cognitive processes by influencing microRNA biogenesis via the use of CRISPR/Cas9 technologies and active mental and physical exercises.

scholarly journals Glycogen Synthase Kinase-3β: A Mediator of Inflammation in Alzheimer's Disease?

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Jari Koistinaho ◽  
Tarja Malm ◽  
Gundars Goldsteins
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glycogen Synthase ◽  
Immune Defense ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Normal Brain ◽  
Brain Functions ◽  
The Brain

Proliferation and activation of microglial cells is a neuropathological characteristic of brain injury and neurodegeneration, including Alzheimer's disease. Microglia act as the first and main form of immune defense in the nervous system. While the primary function of microglia is to survey and maintain the cellular environment optimal for neurons in the brain parenchyma by actively scavenging the brain for damaged brain cells and foreign proteins or particles, sustained activation of microglia may result in high production of proinflammatory mediators that disturb normal brain functions and even cause neuronal injury. Glycogen synthase kinase-3βhas been recently identified as a major regulator of immune system and mediates inflammatory responses in microglia. Glycogen synthase kinase-3βhas been extensively investigated in connection to tau and amyloidβtoxicity, whereas reports on the role of this enzyme in neuroinflammation in Alzheimer's disease are negligible. Here we review and discuss the role of glycogen synthase-3βin immune cells in the context of Alzheimer's disease pathology.

scholarly journals Reading Memory Formation from the Eyes

2018 ◽  
Author(s):  
Anne Bergt ◽  
Anne E. Urai ◽  
Tobias H. Donner ◽  
Lars Schwabe
Keyword(s):  
Synaptic Plasticity ◽  
Memory Formation ◽  
Pupil Dilation ◽  
Long Term Memory ◽  
Term Memory ◽  
Pupil Response ◽  
Rapid Formation ◽  
The Brain

At any time, we are processing thousands of stimuli, but only few of them will be remembered hours or days later. Is there any way to predict which ones? Here, we show that the pupil response to ongoing stimuli, an indicator of physiological arousal, is a reliable predictor of long-term memory for these stimuli, over at least one day. Pupil dilation was tracked while participants performed visual and auditory encoding tasks. Memory was tested immediately after encoding and 24 hours later. Irrespective of the encoding modality, trial-by-trial variations in pupil dilation predicted which stimuli were recalled in the immediate and 24 hours-delayed tests. These results show that our eyes may provide a window into the formation of long-term memories. Furthermore, our findings underline the important role of central arousal systems in the rapid formation of memories in the brain, possibly by gating synaptic plasticity mechanisms.

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