The neuronal network of the endogenous clock

e-Neuroforum ◽  
2010 ◽  
Vol 16 (1) ◽  
Author(s):  
Charlotte Förster
Keyword(s):  
Molecular Basis ◽  
Clock Genes ◽  
Fruit Fly ◽  
Biological Processes ◽  
Rhythm Generation ◽  
The Metabolic Syndrome ◽  
Clock Network ◽  
Endogenous Clock ◽  
The Brain

AbstractEndogenous clocks control the rhythm of many biological processes. Malfunction of endogenous clocks in humans can lead to various diseases as sleep disorders, depres­sions, the metabolic syndrome and cancer. All animals have a main clock in the brain. This clock comprises a network of clock neurons that communicate with each other. In each clock neuron, conserved clock genes and pro­teins interact in to generate a molecular os­cillation. The molecular basis of this rhythm generation as well as the anatomy of the neuronal clock network is best investigated in the fruit fly Drosophila melanogaster. In the little fly, clock genes can be shut down in specific clock neurons. Furthermore, specific clock neurons can be electrically silenced and the rhythmic behaviour of such manipulated flies can be studied. A flurry of recent studies has begun to identify the role of specific clock neurons in the clock network, and these find­ings are helping to understand the basic neu­ronal mechanisms of endogenous clocks.

Organization of endogenous clocks in insects

2005 ◽  
Vol 33 (5) ◽  
pp. 957-961 ◽  
Author(s):  
C. Helfrich-Förster
Keyword(s):  
Drosophila Melanogaster ◽  
Molecular Mechanisms ◽  
Clock Genes ◽  
Fruit Fly ◽  
Circadian Clocks ◽  
Rhythm Generation ◽  
Similarities And Differences ◽  
The Brain ◽  
Master Clock

Insect and mammalian circadian clocks show striking similarities. They utilize homologous clock genes, generating self-sustained circadian oscillations in distinct master clocks of the brain, which then control rhythmic behaviour. The molecular mechanisms of rhythm generation were first uncovered in the fruit fly Drosophila melanogaster, whereas cockroaches were among the first animals where the brain master clock was localized. Despite many similarities, there exist obvious differences in the organization and functioning of insect master clocks. These similarities and differences are reviewed on a molecular and anatomical level.

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 Exaggerated inflammation, impaired host defense, and neuropathology in progranulin-deficient mice

2009 ◽  
Vol 207 (1) ◽  
pp. 117-128 ◽  
Author(s):  
Fangfang Yin ◽  
Rebecca Banerjee ◽  
Bobby Thomas ◽  
Ping Zhou ◽  
Liping Qian ◽  
...  
Keyword(s):  
Host Defense ◽  
Hippocampal Slices ◽  
Interleukin 10 ◽  
Biological Processes ◽  
Listeria Monocytogenes Infection ◽  
The Brain ◽  
Deficient Mice

Progranulin (PGRN) is a widely expressed protein involved in diverse biological processes. Haploinsufficiency of PGRN in the human causes tau-negative, ubiquitin-positive frontotemporal dementia (FTD). However, the mechanisms are unknown. To explore the role of PGRN in vivo, we generated PGRN-deficient mice. Macrophages from these mice released less interleukin-10 and more inflammatory cytokines than wild type (WT) when exposed to bacterial lipopolysaccharide. PGRN-deficient mice failed to clear Listeria monocytogenes infection as quickly as WT and allowed bacteria to proliferate in the brain, with correspondingly greater inflammation than in WT. PGRN-deficient macrophages and microglia were cytotoxic to hippocampal cells in vitro, and PGRN-deficient hippocampal slices were hypersusceptible to deprivation of oxygen and glucose. With age, brains of PGRN-deficient mice displayed greater activation of microglia and astrocytes than WT, and their hippocampal and thalamic neurons accumulated cytosolic phosphorylated transactivation response element DNA binding protein–43. Thus, PGRN is a key regulator of inflammation and plays critical roles in both host defense and neuronal integrity. FTD associated with PGRN insufficiency may result from many years of reduced neutrotrophic support together with cumulative damage in association with dysregulated inflammation.

scholarly journals The role of metabolic syndrome in Alzheimer’s disease

2021 ◽  
Author(s):  
Gláucia Maria Senhorinha ◽  
Arlys Emanuel Mendes da Silva Santos ◽  
Douglas Daniel Dophine
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Alzheimer's Disease ◽  
Metabolic Syndrome ◽  
Brain Regions ◽  
Alzheimer Dementia ◽  
The Metabolic Syndrome ◽  
The Brain

Background: Metabolic syndrome (MS) leads to the deposits formation of insoluble protein aggregates, neuroinflammation, oxidative stress, neuronal insulin resistance, progressive insulin resistance, desensitization and β-amyloid amyloidosis in the brain, besides direct ischemic effects which are closely associated with Alzheimer’s disease (AD).1 Objectives: The present study seeks to understand the role of the metabolic syndrome in the pathophysiology of Alzheimer’s disease and to describe preventive and therapeutic interventions. Methods: PUBMED and Web of Science were the databases used, the following descriptors were used to search the articles: “Alzheimer Disease” OR “Alzheimer Dementia” AND “Metabolic Syndrome”. Results: The studies in general have shown that MS is related to AD through brain insulin resistance, triggered by oxidative stress and neuroinflammation. It is related to the progressive atrophy of brain regions involved in the progression of AD. Insulin resistance in the brain is related to the progressive atrophy of the brain regions from initial progression of AD. These regions are cingulate cortices, medial temporal lobe, prefrontal gyri and other regions.³ Thus, there is an inhibition of the mechanisms of beta-amyloid removal, leading to its accumulation, which generates neuroinflammation, that in turn potentiates insulin resistance in the central nervous system, contributing to the genesis and progression of cognitive damage.2,3 Conclusions: Insulin resistance plays a major role in the initiation and perpetuation of cognitive impairment in AD. Furthermore, the components of the MS associated with AD, when treated with preventive and therapeutic measures, break this association by promoting rebalancing of the metabolism.

scholarly journals The neuropeptide allatostatin C from clock-associated DN1p neurons generates the circadian rhythm for oogenesis

2021 ◽  
Vol 118 (4) ◽  
pp. e2016878118
Author(s):  
Chen Zhang ◽  
Ivana Daubnerova ◽  
Yong-Hoon Jang ◽  
Shu Kondo ◽  
Dušan Žitňan ◽  
...  
Keyword(s):  
Clock Genes ◽  
Biological Clock ◽  
Model Organism ◽  
Fruit Fly ◽  
Neural Substrates ◽  
Pacemaker Neurons ◽  
Insulin Producing Cells ◽  
Gonadotrophin Secretion ◽  
Show Evidence ◽  
The Brain

The link between the biological clock and reproduction is evident in most metazoans. The fruit fly Drosophila melanogaster, a key model organism in the field of chronobiology because of its well-defined networks of molecular clock genes and pacemaker neurons in the brain, shows a pronounced diurnal rhythmicity in oogenesis. Still, it is unclear how the circadian clock generates this reproductive rhythm. A subset of the group of neurons designated “posterior dorsal neuron 1” (DN1p), which are among the ∼150 pacemaker neurons in the fly brain, produces the neuropeptide allatostatin C (AstC-DN1p). Here, we report that six pairs of AstC-DN1p send inhibitory inputs to the brain insulin-producing cells, which express two AstC receptors, star1 and AICR2. Consistent with the roles of insulin/insulin-like signaling in oogenesis, activation of AstC-DN1p suppresses oogenesis through the insulin-producing cells. We show evidence that AstC-DN1p activity plays a role in generating an oogenesis rhythm by regulating juvenile hormone and vitellogenesis indirectly via insulin/insulin-like signaling. AstC is orthologous to the vertebrate neuropeptide somatostatin (SST). Like AstC, SST inhibits gonadotrophin secretion indirectly through gonadotropin-releasing hormone neurons in the hypothalamus. The functional and structural conservation linking the AstC and SST systems suggest an ancient origin for the neural substrates that generate reproductive rhythms.

Role of Extracellular Vesicles in Glioma Progression: Deciphering cellular biological processes to clinical applications

2020 ◽  
Vol 20 ◽  
Author(s):  
Rashmi Rana ◽  
Shikha Joon ◽  
Kirti Chauhan ◽  
Vaishnavi Rathi ◽  
Nirmal Kumar Ganguly ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Targeted Delivery ◽  
Diagnostic Methods ◽  
Treatment Modalities ◽  
Biological Processes ◽  
Diagnostic Biomarkers ◽  
Brain And Spinal Cord ◽  
The Brain ◽  
Glioma Progression

: Glioma predominantly targets glial cells in the brain and spinal cord. There are grade I, II, III, and IV gliomas with anaplastic astrocytoma and glioblastoma multiforme as the most severe forms of the disease. Current diagnostic methods are limited in their data acquisition and interpretation, markedly affecting treatment modalities and patient outcomes. Circulating extracellular vesicles (EVs) or “magic bullets” contain bioactive signature molecules such as DNA, RNA, proteins, lipids, and metabolites. These secretory “smart probes” participate in myriad cellular activities, including glioma progression. EVs are released by all cell populations and may serve as novel diagnostic biomarkers and efficient nanovehicles in the targeted delivery of encapsulated therapeutics. The present review describes the potential of EVbased biomarkers for glioma management.

scholarly journals The Role of Metal Regulatory Proteins in Brain Oxidative Stress: A Tutorial

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Wayne Briner
Keyword(s):  
Oxidative Stress ◽  
Redox Activity ◽  
Biological Processes ◽  
Physiological Processes ◽  
Pharmacological Targets ◽  
Wide Range ◽  
Brain Oxidative Stress ◽  
The Brain ◽  
And Oxidative Stress

The proteins that regulate the metabolism of a metal must also play a role in regulating the redox activity of the metal. Metals are intrinsic to a substantial number of biological processes and the proteins that regulate those activities are also considerable in number. The role these proteins play in a wide range of physiological processes involves them directly and indirectly in a variety of disease processes. Similarly, it may be therapeutically advantageous to pharmacologically alter the activity of these metal containing proteins to influence disease processes. This paper will introduce the reader to a number of important proteins in both metal metabolism and oxidative stress, with an emphasis on the brain. Potential pharmacological targets will be considered.

Back to the basics? Transcriptomics offers integrative insights into the role of space, time and the environment for gene expression and behaviour

2021 ◽  
Vol 17 (9) ◽  
pp. 20210293
Author(s):  
Eva K. Fischer ◽  
Mark E. Hauber ◽  
Alison M. Bell
Keyword(s):  
Gene Expression ◽  
Rna Sequencing ◽  
Molecular Basis ◽  
Gene Activation ◽  
Rna Expression ◽  
Brain Gene Expression ◽  
Explicit Consideration ◽  
The Brain ◽  
Genomic Revolution

Fuelled by the ongoing genomic revolution, broadscale RNA expression surveys are fast replacing studies targeting one or a few genes to understand the molecular basis of behaviour. Yet, the timescale of RNA-sequencing experiments and the dynamics of neural gene activation are insufficient to drive real-time switches between behavioural states. Moreover, the spatial, functional and transcriptional complexity of the brain (the most commonly targeted tissue in studies of behaviour) further complicates inference. We argue that a Central Dogma-like ‘back-to-basics’ assumption that gene expression changes cause behaviour leaves some of the most important aspects of gene–behaviour relationships unexplored, including the roles of environmental influences, timing and feedback from behaviour—and the environmental shifts it causes—to neural gene expression. No perfect experimental solutions exist but we advocate that explicit consideration, exploration and discussion of these factors will pave the way toward a richer understanding of the complicated relationships between genes, environments, brain gene expression and behaviour over developmental and evolutionary timescales.

scholarly journals Death-Associated Protein Kinase 1 Phosphorylation in Neuronal Cell Death and Neurodegenerative Disease

2019 ◽  
Vol 20 (13) ◽  
pp. 3131 ◽  
Author(s):  
Nami Kim ◽  
Dongmei Chen ◽  
Xiao Zhen Zhou ◽  
Tae Ho Lee
Keyword(s):  
Cell Death ◽  
Protein Kinase ◽  
Neurodegenerative Diseases ◽  
Molecular Mechanisms ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Biological Processes ◽  
Death Associated Protein Kinase ◽  
The Brain

Regulated neuronal cell death plays an essential role in biological processes in normal physiology, including the development of the nervous system. However, the deregulation of neuronal apoptosis by various factors leads to neurodegenerative diseases such as ischemic stroke and Alzheimer’s disease (AD). Death-associated protein kinase 1 (DAPK1) is a calcium/calmodulin (Ca2+/CaM)-dependent serine/threonine (Ser/Thr) protein kinase that activates death signaling and regulates apoptotic neuronal cell death. Although DAPK1 is tightly regulated under physiological conditions, DAPK1 deregulation in the brain contributes to the development of neurological disorders. In this review, we describe the molecular mechanisms of DAPK1 regulation in neurons under various stresses. We also discuss the role of DAPK1 signaling in the phosphorylation-dependent and phosphorylation-independent regulation of its downstream targets in neuronal cell death. Moreover, we focus on the major impact of DAPK1 deregulation on the progression of neurodegenerative diseases and the development of drugs targeting DAPK1 for the treatment of diseases. Therefore, this review summarizes the DAPK1 phosphorylation signaling pathways in various neurodegenerative diseases.

scholarly journals DNA demethylation switches the drivers of Foxp3 expression to maintain regulatory T cell identity

2020 ◽  
Author(s):  
Jun Li ◽  
Beisi Xu ◽  
Xinying Zong ◽  
Minghong He ◽  
Yiping Fan ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Cell Fate ◽  
Regulatory T Cell ◽  
Molecular Basis ◽  
Foxp3 Expression ◽  
Chromatin Accessibility ◽  
Dna Demethylation ◽  
Biological Processes ◽  
Regulatory Mode

ABSTRACTMaintenance of differentiated cellular states is crucial for numerous biological processes, yet its molecular basis remains unclear. Here, we investigate how mechanistically regulatory T (Treg) cell fate is “locked in” during lineage commitment via transcriptional regulation of its lineage-specifying factor Foxp3. Tet-mediated DNA demethylation ofFoxp3enhancer CNS2 was proposed to be a key mechanism maintaining Foxp3 transcription. However, this model has not been directly tested. Therefore, we integrated genetic, pharmacological, and epigenetic approaches to examine the function and mechanism of DNA demethylation in Treglineage maintenance. We observed an abrupt switch of the transcriptional drivers of Foxp3 upon DNA demethylation, which was abolished by CNS2 deficiency. Demethylation of CNS2 increased chromatin accessibility and protein binding, conferring on Tregfate substantial resistance to adverse environments. Thus, our study consolidated the role of DNA demethylation in stabilizing Foxp3 expression incisand revealed a novel regulatory mode governing Tregidentity.

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