scholarly journals The role of cellular development and cell death in neurochemical organization and integrative brain functions: Normal and pathological

2004 ◽  
Vol 57 (3-4) ◽  
pp. 120-124 ◽  
Author(s):  
Vladimir Sherstnev
Keyword(s):  
Experimental Study ◽  
Learning And Memory ◽  
Molecular Mechanisms ◽  
Prognostic Markers ◽  
Brain Functions ◽  
System A ◽  
Cellular Development ◽  
Mechanisms Of Development ◽  
Apoptotic Factors

In terms of systemic aspects of common molecular mechanisms of development, important part of which is the process of cellular death and integrative activity of nervous system, a omplex clinical-experimental study of effects of various neurotrophic and apoptotic factors (proteins S100b, HLDF, brain lectins CSL and R1) on learning and memory and ishemic stroke was performed. Data concerning specific and heterochronic participation of these factors in neurochemical mechanisms of learning and memory in mechanisms of ishemic stroke formation were established. Changes of examined factors and their antibodies as well as the dynamics of changes in sera and cerebro spinal fluid can be considered as prognostic markers of ischemic stroke and efficiency of therapy.

scholarly journals Glymphatic System in the Central Nervous System, a Novel Therapeutic Direction Against Brain Edema After Stroke

2021 ◽  
Vol 13 ◽  
Author(s):  
Xiangyue Zhou ◽  
Youwei Li ◽  
Cameron Lenahan ◽  
Yibo Ou ◽  
Minghuan Wang ◽  
...  
Keyword(s):  
Brain Edema ◽  
Brain Tissue ◽  
Molecular Mechanisms ◽  
Glymphatic System ◽  
System A ◽  
Function Recovery ◽  
The Central Nervous System ◽  
The Stability ◽  
The Brain

Stroke is the destruction of brain function and structure, and is caused by either cerebrovascular obstruction or rupture. It is a disease associated with high mortality and disability worldwide. Brain edema after stroke is an important factor affecting neurologic function recovery. The glymphatic system is a recently discovered cerebrospinal fluid (CSF) transport system. Through the perivascular space and aquaporin 4 (AQP4) on astrocytes, it promotes the exchange of CSF and interstitial fluid (ISF), clears brain metabolic waste, and maintains the stability of the internal environment within the brain. Excessive accumulation of fluid in the brain tissue causes cerebral edema, but the glymphatic system plays an important role in the process of both intake and removal of fluid within the brain. The changes in the glymphatic system after stroke may be an important contributor to brain edema. Understanding and targeting the molecular mechanisms and the role of the glymphatic system in the formation and regression of brain edema after stroke could promote the exclusion of fluids in the brain tissue and promote the recovery of neurological function in stroke patients. In this review, we will discuss the physiology of the glymphatic system, as well as the related mechanisms and therapeutic targets involved in the formation of brain edema after stroke, which could provide a new direction for research against brain edema after stroke.

scholarly journals Neuronal megalin mediates synaptic plasticity—a novel mechanism underlying intellectual disabilities in megalin gene pathologies

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
João R Gomes ◽  
Andrea Lobo ◽  
Renata Nogueira ◽  
Ana F Terceiro ◽  
Susete Costelha ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Intellectual Disabilities ◽  
Learning And Memory ◽  
Neuronal Activity ◽  
Hippocampal Neurons ◽  
Molecular Mechanisms ◽  
Genetic Disorder ◽  
Cell Surface Receptor ◽  
Neuronal Cultures

Abstract Donnai-Barrow syndrome, a genetic disorder associated to LRP2 (low-density lipoprotein receptor 2/megalin) mutations, is characterized by unexplained neurological symptoms and intellectual deficits. Megalin is a multifunctional endocytic clearance cell-surface receptor, mostly described in epithelial cells. This receptor is also expressed in the CNS, mainly in neurons, being involved in neurite outgrowth and neuroprotective mechanisms. Yet, the mechanisms involved in the regulation of megalin in the CNS are poorly understood. Using transthyretin knockout mice, a megalin ligand, we found that transthyretin positively regulates neuronal megalin levels in different CNS areas, particularly in the hippocampus. Transthyretin is even able to rescue megalin downregulation in transthyretin knockout hippocampal neuronal cultures, in a positive feedback mechanism via megalin. Importantly, transthyretin activates a regulated intracellular proteolysis mechanism of neuronal megalin, producing an intracellular domain, which is translocated to the nucleus, unveiling megalin C-terminal as a potential transcription factor, able to regulate gene expression. We unveil that neuronal megalin reduction affects physiological neuronal activity, leading to decreased neurite number, length and branching, and increasing neuronal susceptibility to a toxic insult. Finally, we unravel a new unexpected role of megalin in synaptic plasticity, by promoting the formation and maturation of dendritic spines, and contributing for the establishment of active synapses, both in in vitro and in vivo hippocampal neurons. Moreover, these structural and synaptic roles of megalin impact on learning and memory mechanisms, since megalin heterozygous mice show hippocampal-related memory and learning deficits in several behaviour tests. Altogether, we unveil a complete novel role of megalin in the physiological neuronal activity, mainly in synaptic plasticity with impact in learning and memory. Importantly, we contribute to disclose the molecular mechanisms underlying the cognitive and intellectual disabilities related to megalin gene pathologies.

scholarly journals Role of Network Science in the Study of Anesthetic State Transitions

2018 ◽  
Vol 129 (5) ◽  
pp. 1029-1044 ◽  
Author(s):  
UnCheol Lee ◽  
George A. Mashour
Keyword(s):  
General Anesthesia ◽  
Molecular Mechanisms ◽  
Network Science ◽  
State Transitions ◽  
General Anesthetics ◽  
Network Efficiency ◽  
Cortical Dynamics ◽  
Brain Functions ◽  
Complex Interactions

Abstract The heterogeneity of molecular mechanisms, target neural circuits, and neurophysiologic effects of general anesthetics makes it difficult to develop a reliable and drug-invariant index of general anesthesia. No single brain region or mechanism has been identified as the neural correlate of consciousness, suggesting that consciousness might emerge through complex interactions of spatially and temporally distributed brain functions. The goal of this review article is to introduce the basic concepts of networks and explain why the application of network science to general anesthesia could be a pathway to discover a fundamental mechanism of anesthetic-induced unconsciousness. This article reviews data suggesting that reduced network efficiency, constrained network repertoires, and changes in cortical dynamics create inhospitable conditions for information processing and transfer, which lead to unconsciousness. This review proposes that network science is not just a useful tool but a necessary theoretical framework and method to uncover common principles of anesthetic-induced unconsciousness.

Molecular Biological Investigations into the Role of the NMDA Receptor in the Pathophysiology of Schizophrenia

1997 ◽  
Vol 31 (1) ◽  
pp. 17-26 ◽  
Author(s):  
Stanley V. Catts ◽  
Phillip B. Ward ◽  
Andrew Lloyd ◽  
Xu Feng Huang ◽  
Gavin Dixon ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Brain Development ◽  
Learning And Memory ◽  
Neural Plasticity ◽  
Molecular Mechanisms ◽  
Postmortem Brain ◽  
Normal Brain ◽  
Postmortem Brain Tissue ◽  
Synaptic Pathology

Objective:There is increasing acceptance that schizophrenia is associated with a generalised disorder in cortical neurodevelopment. The aim of this paper is to review the evidence that this disorder may be accounted for by abnormalities in mechanisms mediated by the main family of excitatory neuroreceptors in cortical brain systems, the N-methyl-D-aspartate (NMDA) glutamatergic receptors. Method:The neurobiological evidence is presented for an abnormality in cortical development related to synaptic pathology in schizophrenia. The unique functions of the NMDA receptor in information processing are described, especially its role in learning and memory, and in neural plasticity and brain development. It is argued that the cellular and molecular mechanisms which underlie learning and memory also govern normal brain development. Studies examining abnormalities in glutamatergic transmission in schizophrenia are reviewed. Results:There is a substantial literature in support of the possibility that NMDA receptor abnormalities may be involved in the neurodevelopmental predisposition to schizophrenia, as well as in symptom production. Conclusions:Research to determine the role of the NMDA receptor in the pathophysiology of schizophrenia is warranted and now feasible. To be successful, this research will require the application of molecular biology techniques to postmortem brain tissue studies, in addition to traditional histochemical approaches.

scholarly journals Role of SNAREs in Neurodegenerative Diseases

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 991
Author(s):  
Azzurra Margiotta
Keyword(s):  
Neurodegenerative Diseases ◽  
Molecular Mechanisms ◽  
Vesicle Fusion ◽  
Snare Complex ◽  
Snare Proteins ◽  
Vesicle Recycling ◽  
Brain Functions ◽  
Progressive Degeneration ◽  
Altered Regulation

Neurodegenerative diseases are pathologies of the central and peripheral nervous systems characterized by loss of brain functions and problems in movement which occur due to the slow and progressive degeneration of cellular elements. Several neurodegenerative diseases are known such as Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis and many studies on the molecular mechanisms underlying these pathologies have been conducted. Altered functions of some key proteins and the presence of intraneuronal aggregates have been identified as responsible for the development of the diseases. Interestingly, the formation of the SNARE complex has been discovered to be fundamental for vesicle fusion, vesicle recycling and neurotransmitter release. Indeed, inhibition of the formation of the SNARE complex, defects in the SNARE-dependent exocytosis and altered regulation of SNARE-mediated vesicle fusion have been associated with neurodegeneration. In this review, the biological aspects of neurodegenerative diseases and the role of SNARE proteins in relation to the onset of these pathologies are described.

scholarly journals GRIP1 regulates synaptic plasticity and learning and memory

2020 ◽  
Vol 117 (40) ◽  
pp. 25085-25091
Author(s):  
Han L. Tan ◽  
Shu-Ling Chiu ◽  
Qianwen Zhu ◽  
Richard L. Huganir
Keyword(s):  
Synaptic Plasticity ◽  
Learning And Memory ◽  
Molecular Mechanisms ◽  
Long Term Potentiation ◽  
Postsynaptic Membrane ◽  
Interacting Protein ◽  
Synaptic Targeting ◽  
Brain Functions ◽  
Ampar Trafficking

Hebbian plasticity is a key mechanism for higher brain functions, such as learning and memory. This form of synaptic plasticity primarily involves the regulation of synaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) abundance and properties, whereby AMPARs are inserted into synapses during long-term potentiation (LTP) or removed during long-term depression (LTD). The molecular mechanisms underlying AMPAR trafficking remain elusive, however. Here we show that glutamate receptor interacting protein 1 (GRIP1), an AMPAR-binding protein shown to regulate the trafficking and synaptic targeting of AMPARs, is required for LTP and learning and memory. GRIP1 is recruited into synapses during LTP, and deletion of Grip1 in neurons blocks synaptic AMPAR accumulation induced by glycine-mediated depolarization. In addition, Grip1 knockout mice exhibit impaired hippocampal LTP, as well as deficits in learning and memory. Mechanistically, we find that phosphorylation of serine-880 of the GluA2 AMPAR subunit (GluA2-S880) is decreased while phosphorylation of tyrosine-876 on GluA2 (GluA2-Y876) is elevated during chemically induced LTP. This enhances the strength of the GRIP1–AMPAR association and, subsequently, the insertion of AMPARs into the postsynaptic membrane. Together, these results demonstrate an essential role of GRIP1 in regulating AMPAR trafficking during synaptic plasticity and learning and memory.

Learning and memory formation in the honeybee (Apis mellifera) and its dependency on the cAMP-protein kinase A pathway

2006 ◽  
Vol 56 (2) ◽  
pp. 259-278 ◽  
Author(s):  
Dorothea Eisenhardt
Keyword(s):  
Apis Mellifera ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Learning And Memory ◽  
Molecular Mechanisms ◽  
Memory Formation ◽  
Olfactory Conditioning ◽  
Proboscis Extension Response ◽  
Kinase A

AbstractThe honeybee (Apis mellifera) is a model organism for the study of learning and memory formation and its underlying mechanisms. Honeybees have a rich behaviour that can be studied in the field as well as in the laboratory. In the latter case, olfactory conditioning of the proboscis extension response (PER) has been intensively studied with respect to the neuronal and molecular mechanisms underlying acquisition and memory formation. Quite a lot is known about the neuronal pathways of both the unconditioned and the conditioned stimulus, and molecular mechanisms that lead to memory formation have been identified. In particular, the role of the cAMP-protein kinase A pathway in memory formation has been analysed. Present knowledge about the molecular basis of memory formation is outlined here. The role of the cAMP-dependent signalling cascade in memory formation is summarised and the activation of this pathway by non-associative and associative learning is discussed.

How do histone modifications contribute to transgenerational epigenetic inheritance in C. elegans?

2020 ◽  
Vol 48 (3) ◽  
pp. 1019-1034 ◽  
Author(s):  
Rachel M. Woodhouse ◽  
Alyson Ashe
Keyword(s):  
Histone Modifications ◽  
Molecular Mechanisms ◽  
Epigenetic Inheritance ◽  
Nematode Caenorhabditis Elegans ◽  
Histone Methyltransferases ◽  
Transgenerational Epigenetic Inheritance ◽  
C Elegans ◽  
Recent Developments ◽  
Gene Regulatory

Gene regulatory information can be inherited between generations in a phenomenon termed transgenerational epigenetic inheritance (TEI). While examples of TEI in many animals accumulate, the nematode Caenorhabditis elegans has proven particularly useful in investigating the underlying molecular mechanisms of this phenomenon. In C. elegans and other animals, the modification of histone proteins has emerged as a potential carrier and effector of transgenerational epigenetic information. In this review, we explore the contribution of histone modifications to TEI in C. elegans. We describe the role of repressive histone marks, histone methyltransferases, and associated chromatin factors in heritable gene silencing, and discuss recent developments and unanswered questions in how these factors integrate with other known TEI mechanisms. We also review the transgenerational effects of the manipulation of histone modifications on germline health and longevity.

Mesophyll conductance: the leaf corridors for photosynthesis

2020 ◽  
Vol 48 (2) ◽  
pp. 429-439 ◽  
Author(s):  
Jorge Gago ◽  
Danilo M. Daloso ◽  
Marc Carriquí ◽  
Miquel Nadal ◽  
Melanie Morales ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Main Role ◽  
Mesophyll Conductance ◽  
Future Studies ◽  
Cell Structures ◽  
Leaf Tissues ◽  
Change Framework ◽  
Chloroplast Stroma

Besides stomata, the photosynthetic CO2 pathway also involves the transport of CO2 from the sub-stomatal air spaces inside to the carboxylation sites in the chloroplast stroma, where Rubisco is located. This pathway is far to be a simple and direct way, formed by series of consecutive barriers that the CO2 should cross to be finally assimilated in photosynthesis, known as the mesophyll conductance (gm). Therefore, the gm reflects the pathway through different air, water and biophysical barriers within the leaf tissues and cell structures. Currently, it is known that gm can impose the same level of limitation (or even higher depending of the conditions) to photosynthesis than the wider known stomata or biochemistry. In this mini-review, we are focused on each of the gm determinants to summarize the current knowledge on the mechanisms driving gm from anatomical to metabolic and biochemical perspectives. Special attention deserve the latest studies demonstrating the importance of the molecular mechanisms driving anatomical traits as cell wall and the chloroplast surface exposed to the mesophyll airspaces (Sc/S) that significantly constrain gm. However, even considering these recent discoveries, still is poorly understood the mechanisms about signaling pathways linking the environment a/biotic stressors with gm responses. Thus, considering the main role of gm as a major driver of the CO2 availability at the carboxylation sites, future studies into these aspects will help us to understand photosynthesis responses in a global change framework.

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