scholarly journals PUFA and their derivatives in neurotransmission and synapses: a new hallmark of synaptopathies

2020 ◽  
Vol 79 (4) ◽  
pp. 388-403
Author(s):  
Mathieu Di Miceli ◽  
Clémentine Bosch-Bouju ◽  
Sophie Layé
Keyword(s):  
Synapse Formation ◽  
Synaptic Function ◽  
Past Century ◽  
High Concentration ◽  
Dietary Pufa ◽  
Synaptic Functions ◽  
Neuropsychiatric Diseases ◽  
Optimal Function ◽  
The Brain

PUFA of the n-3 and n-6 families are present in high concentration in the brain where they are major components of cell membranes. The main forms found in the brain are DHA (22 :6, n-3) and arachidonic acid (20:4, n-6). In the past century, several studies pinpointed that modifications of n-3 and n-6 PUFA levels in the brain through dietary supply or genetic means are linked to the alterations of synaptic function. Yet, synaptopathies emerge as a common characteristic of neurodevelopmental disorders, neuropsychiatric diseases and some neurodegenerative diseases. Understanding the mechanisms of action underlying the activity of PUFA at the level of synapses is thus of high interest. In this frame, dietary supplementation in PUFA aiming at restoring or promoting the optimal function of synapses appears as a promising strategy to treat synaptopathies. This paper reviews the link between dietary PUFA, synapse formation and the role of PUFA and their metabolites in synaptic functions.

scholarly journals Synaptic Paths to Neurodegeneration: The Emerging Role of TDP-43 and FUS in Synaptic Functions

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Shuo-Chien Ling
Keyword(s):  
Low Complexity ◽  
Synaptic Function ◽  
Early Event ◽  
Separation Mechanism ◽  
Liquid Droplets ◽  
Fused In Sarcoma ◽  
Synaptic Functions ◽  
Rna Targets ◽  
Rnp Granules

TAR DNA-binding protein-43 KDa (TDP-43) and fused in sarcoma (FUS) as the defining pathological hallmarks for amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), coupled with ALS-FTD-causing mutations in both genes, indicate that their dysfunctions damage the motor system and cognition. On the molecular level, TDP-43 and FUS participate in the biogenesis and metabolism of coding and noncoding RNAs as well as in the transport and translation of mRNAs as part of cytoplasmic mRNA-ribonucleoprotein (mRNP) granules. Intriguingly, many of the RNA targets of TDP-43 and FUS are involved in synaptic transmission and plasticity, indicating that synaptic dysfunction could be an early event contributing to motor and cognitive deficits in ALS and FTD. Furthermore, the ability of the low-complexity prion-like domains of TDP-43 and FUS to form liquid droplets suggests a potential mechanism for mRNP assembly and conversion. This review will discuss the role of TDP-43 and FUS in RNA metabolism, with an emphasis on the involvement of this process in synaptic function and neuroprotection. This will be followed by a discussion of the potential phase separation mechanism for forming RNP granules and pathological inclusions.

The role of support cells in the growth and differentiation of neurones in the abdominal ganglion of Aplysia

1981 ◽  
Vol 95 (1) ◽  
pp. 205-214
Author(s):  
S. M. Schacher
Keyword(s):  
Cell Body ◽  
Synapse Formation ◽  
Sea Water ◽  
Secretory Granules ◽  
Body Growth ◽  
Abdominal Ganglion ◽  
Morphological Properties ◽  
High Concentration ◽  
Premature Release

During the late premetamorphic stages of development, the abdominal ganglion of Aplysia is surrounded by a group of support cells which later develop morphological properties characteristic of glial cells. These support cells contain large secretory granules whose contents are released primarily after the onset of the metamorphic phase. The release of the granule contents may signal the burst of neuronal growth and maturation that occurs following metamorphosis. The evidence supporting this idea is the following: (1) The release of the granule material after the onset of metamorphosis coincides with an increase in cell body growth and a more marked increase in the density of synapses within the neuropil. Both release and neuronal maturation can be blocked when metamorphosis is postponed by withholding the appropriate macroalgal substrate. (2) Premature release of the granule contents 2-3 weeks before metamorphosis with artificial sea water containing a high concentration of potassium results in an increase in cell body growth, density of synapses, and the number of spines formed and contacts received by specific identified cells. (3) Artificially inducing the release of the granule material in animals whose metamorphosis has been prevented (by withholding the appropriate substrate) still produces an increase in cell body growth and density of synapses. These results suggest that the release of material from support cell granules provides a general stimulus for neuronal differentiation including cell body growth, spine development, and synapse formation.

scholarly journals Dynamic N6-methyladenosine RNA methylation in brain and diseases

Epigenomics ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 371-380 ◽  
Author(s):  
Andrew M Shafik ◽  
Emily G Allen ◽  
Peng Jin
Keyword(s):  
Brain Development ◽  
Rna Modification ◽  
Normal Brain ◽  
Biological Processes ◽  
Future Directions ◽  
Body Of Knowledge ◽  
Neuropsychiatric Diseases ◽  
The Brain ◽  
Normal Brain Development

N6-methyladenosine (m6A) is a dynamic RNA modification that regulates various aspects of RNA metabolism and has been implicated in many biological processes and transitions. m6A is highly abundant in the brain; however, only recently has the role of m6A in brain development been a focus. The machinery that controls m6A is critically important for proper neurodevelopment, and the precise mechanisms by which m6A regulates these processes are starting to emerge. However, the role of m6A in neurodegenerative and neuropsychiatric diseases still requires much elucidation. This review discusses and summarizes the current body of knowledge surrounding the function of the m6A modification in regulating normal brain development, neurodegenerative diseases and outlines possible future directions.

scholarly journals Fractalkine Attenuates Microglial Cell Activation Induced by Prenatal Stress

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Joanna Ślusarczyk ◽  
Ewa Trojan ◽  
Katarzyna Głombik ◽  
Katarzyna Chamera ◽  
Adam Roman ◽  
...  
Keyword(s):  
Prenatal Stress ◽  
Cell Activation ◽  
Inflammatory Factors ◽  
Potential Contribution ◽  
Fractalkine Receptor ◽  
Neuropsychiatric Diseases ◽  
Prenatally Stressed ◽  
The Brain ◽  
Receptor Cx3cr1

The potential contribution of inflammation to the development of neuropsychiatric diseases has recently received substantial attention. In the brain, the main immune cells are the microglia. As they are the main source of inflammatory factors, it is plausible that the regulation of their activation may be a potential therapeutic target. Fractalkine (CX3CL1) and its receptor CX3CR1 play a crucial role in the control of the biological activity of the microglia. In the present study, using microglial cultures we investigated whether fractalkine is able to reverse changes in microglia caused by a prenatal stress procedure. Our study found that the microglia do not express fractalkine. Prenatal stress decreases the expression of the fractalkine receptor, which in turn is enhanced by the administration of exogenous fractalkine. Moreover, treatment with fractalkine diminishes the prenatal stress-induced overproduction of proinflammatory factors such as IL-1β, IL-18, IL-6, TNF-α, CCL2, or NO in the microglial cells derived from prenatally stressed newborns. In conclusion, the present results revealed that the pathological activation of microglia in prenatally stressed newborns may be attenuated by fractalkine administration. Therefore, understanding of the role of the CX3CL1-CX3CR1 system may help to elucidate the mechanisms underlying the neuron-microglia interaction and its role in pathological conditions in the brain.

scholarly journals ADAM10- and presenilin 1/γ-secretase-dependent cleavage of PTPRT mitigates neurodegeneration of Alzheimer’s disease

2021 ◽  
Author(s):  
Siling Liu ◽  
Zhongyu Zhang ◽  
Lianwei Li ◽  
Li Yao ◽  
Zhanshan Ma ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Synapse Formation ◽  
Transmembrane Protein ◽  
Synaptic Function ◽  
Presenilin 1 ◽  
Behavioral Deficits ◽  
Altered Gene

AbstractPTPRT (receptor-type tyrosine-protein phosphatase T), as a brain-specific type 1 transmembrane protein, plays an important function in neurodevelopment and synapse formation. Here, we identified that PTPRT is a novel substrate of ADAM10- and presenilin 1/γ-secretase. The intracellular domain (PICD), which was released from the cleavage of PTPRT, translocated to the nucleus and dephosphorylated signal transducer and activator of transcription 3 (pSTAT3Y705). Overexpression of the PICD alone profoundly altered gene expression in neuronal cells. We further found that the downregulation of Ptprt expression was negatively correlated to the accumulation of pSTAT3Y705 in the brains of human Alzheimer’s disease (AD) and model mice. PICD alone not only decreased pSTAT3Y705 and Aβ deposition but also markedly improved synaptic function and behavioral deficits in APP/PS1 mice. Our data demonstrate a distinct role of the ADAM 10- and presenilin 1/γ-secretase-dependent cleavage of PTPRT in mitigating neurodegeneration of Alzheimer’s disease.

scholarly journals Role of Adenosine A2AReceptors in Modulating Synaptic Functions and Brain Levels of BDNF: a Possible Key Mechanism in the Pathophysiology of Huntington's Disease

2010 ◽  
Vol 10 ◽  
pp. 1768-1782 ◽  
Author(s):  
Maria Teresa Tebano ◽  
Alberto Martire ◽  
Valentina Chiodi ◽  
Antonella Ferrante ◽  
Patrizia Popoli
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Pathogenetic Role ◽  
Protein Levels ◽  
Synaptic Functions ◽  
Disease Therapy ◽  
Pka Pathway ◽  
The Brain ◽  
Permissive Role

In the last few years, accumulating evidence has shown the existence of an important cross-talk between adenosine A2Areceptors (A2ARs) and brain-derived neurotrophic factor (BDNF). Not only are A2ARs involved in the mechanism of transactivation of BDNF receptor TrkB, they also modulate the effect of BDNF on synaptic transmission, playing a facilitatory and permissive role. The cAMP-PKA pathway, the main transduction system operated by A2ARs, is involved in such effects. Furthermore, a basal tonus of A2ARs is required to allow the regulation of BDNF physiological levels in the brain, as demonstrated by the reduced protein levels measured in A2ARs KO mice. The crucial role of adenosine A2ARs in the maintenance of synaptic functions and BDNF levels will be reviewed here and discussed in the light of possible implications for Huntington's disease therapy, in which a joint impairment of BDNF and A2ARs seems to play a pathogenetic role.

scholarly journals Active Forgetting: Adaptation of Memory by Prefrontal Control

2021 ◽  
Vol 72 (1) ◽  
pp. 1-36 ◽  
Author(s):  
Michael C. Anderson ◽  
Justin C. Hulbert
Keyword(s):  
Emotional State ◽  
Memory Loss ◽  
Brain Structures ◽  
Past Century ◽  
Top Down ◽  
The Past ◽  
New Findings ◽  
Nonhuman Animals ◽  
The Brain

Over the past century, psychologists have discussed whether forgetting might arise from active mechanisms that promote memory loss to achieve various functions, such as minimizing errors, facilitating learning, or regulating one's emotional state. The past decade has witnessed a great expansion in knowledge about the brain mechanisms underlying active forgetting in its varying forms. A core discovery concerns the role of the prefrontal cortex in exerting top-down control over mnemonic activity in the hippocampus and other brain structures, often via inhibitory control. New findings reveal that such processes not only induce forgetting of specific memories but also can suppress the operation of mnemonic processes more broadly, triggering windows of anterograde and retrograde amnesia in healthy people. Recent work extends active forgetting to nonhuman animals, presaging the development of a multilevel mechanistic account that spans the cognitive, systems, network, and even cellular levels. This work reveals how organisms adapt their memories to their cognitive and emotional goals and has implications for understanding vulnerability to psychiatric disorders.

The role of neuronal versus astrocyte-derived heparan sulfate proteoglycans in brain development and injury

2014 ◽  
Vol 42 (5) ◽  
pp. 1263-1269 ◽  
Author(s):  
Isabella Farhy Tselnicker ◽  
Matthew M. Boisvert ◽  
Nicola J. Allen
Keyword(s):  
Heparan Sulfate ◽  
Synapse Formation ◽  
Heparan Sulfate Proteoglycans ◽  
Synaptic Function ◽  
Current Evidence ◽  
Cell Type ◽  
Injury Response ◽  
Specific Expression ◽  
Core Proteins ◽  
The Brain

Astrocytes modulate many aspects of neuronal function, including synapse formation and the response to injury. Heparan sulfate proteoglycans (HSPGs) mediate some of the effects of astrocytes on synaptic function, and participate in the astrocyte-mediated brain injury response. HSPGs are a highly conserved class of proteoglycans, with variable heparan sulfate (HS) chains that play a major role in determining the function of these proteins, such as binding to growth factors and receptors. Expression of both the core proteins and their HS chains can vary depending on cellular origin, thus the functional impact of HSPGs may be determined by the cell type in which they are expressed. In the brain, HSPGs are expressed by both neurons and astrocytes; however, the specific contribution of neuronal HSPGs compared with astrocyte-derived HSPGs to development and the injury response is largely unknown. The present review examines the current evidence regarding the roles of HSPGs in the brain, describes the cellular origins of HSPGs, and interrogates the roles of HSPGs from astrocytes and neurons in synaptogenesis and injury. The importance of considering cell-type-specific expression of HSPGs when studying brain function is discussed.

scholarly journals The role of pathological tau in synaptic dysfunction in Alzheimer’s diseases

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Moxin Wu ◽  
Manqing Zhang ◽  
Xiaoping Yin ◽  
Kai Chen ◽  
Zhijian Hu ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Dendritic Spines ◽  
Amyloid Β ◽  
Synaptic Function ◽  
Synaptic Dysfunction ◽  
Novel Therapeutic Strategies ◽  
And Function ◽  
The Brain ◽  
Pathological Event

AbstractAlzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive cognitive decline, accompanied by amyloid-β (Aβ) overload and hyperphosphorylated tau accumulation in the brain. Synaptic dysfunction, an important pathological hallmark in AD, is recognized as the main cause of the cognitive impairments. Accumulating evidence suggests that synaptic dysfunction could be an early pathological event in AD. Pathological tau, which is detached from axonal microtubules and mislocalized into pre- and postsynaptic neuronal compartments, is suggested to induce synaptic dysfunction in several ways, including reducing mobility and release of presynaptic vesicles, decreasing glutamatergic receptors, impairing the maturation of dendritic spines at postsynaptic terminals, disrupting mitochondrial transport and function in synapses, and promoting the phagocytosis of synapses by microglia. Here, we review the current understanding of how pathological tau mediates synaptic dysfunction and contributes to cognitive decline in AD. We propose that elucidating the mechanism by which pathological tau impairs synaptic function is essential for exploring novel therapeutic strategies for AD.

scholarly journals Synapse molecular complexity and the plasticity behaviour problem

2018 ◽  
Vol 2 ◽  
pp. 239821281881068 ◽  
Author(s):  
Seth G. N. Grant
Keyword(s):  
Synaptic Function ◽  
Brain Diseases ◽  
Behaviour Problem ◽  
Excitatory Synapses ◽  
Existential Crisis ◽  
Full Complement ◽  
Molecular Complexity ◽  
The Brain ◽  
Computational Properties

Synapses are the hallmark of brain complexity and have long been thought of as simple connectors between neurons. We are now in an era in which we know the full complement of synapse proteins and this has created an existential crisis because the molecular complexity far exceeds the requirements of most simple models of synaptic function. Studies of the organisation of proteome complexity and its evolution provide surprising new insights that challenge existing dogma and promote the development of new theories about the origins and role of synapses in behaviour. The postsynaptic proteome of excitatory synapses is a structure with high molecular complexity and sophisticated computational properties that is disrupted in over 130 brain diseases. A key goal of 21st-century neuroscience is to develop comprehensive molecular datasets on the brain and develop theories that explain the molecular basis of behaviour.

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