scholarly journals The murburn precepts for photoreception

2020 ◽  
Author(s):  
Kelath Murali Manoj ◽  
Vivian David Jacob
Keyword(s):  
Oxygen Demand ◽  
Oxygenic Photosynthesis ◽  
Neural Cells ◽  
Toxic Product ◽  
Cone Cells ◽  
Dose Responses ◽  
High Oxygen Demand ◽  
Electron Transfers ◽  
The Brain ◽  
Electric Activation

Murburn concept is a redox mechanistic scheme involving interactive equilibriums of discretized or organized proteins/substrates molecules, unbound ions and radicals (or reactive species); which may afford selective/specific electron transfers, particularly at phospholipid interfaces. Earlier, we have applied murburn concept to provide parsimonious explanations (grounded in thermodynamics and kinetics) for various physiological/bioenergetic routines like xenobiotic metabolism, unusual dose responses, aerobic respiration, thermogenesis, homeostasis, trans-membrane potential, oxygenic photosynthesis, etc. While proposing the murburn model for photophosphorylation, we had projected that the murburn mechanism could also be relevant for photoreception physiology. Herein, we expand on this aspect and present the basic scheme and evidence in support for the murburn model of photoreception, with retinal/opsin as the salient photon-impingement response-transducing element. In alignment with our earlier murburn schemes, we propose that diffusible reactive oxygen species (DROS, as exemplified by superoxide, which is currently deemed a toxic product of all-trans retinal and NADPH oxidase interactions) is produced in rod/cone cells upon photoactivation and it plays a crucial role in the visual cycle. This is supported by the fact that layers of photoreceptive neural cells precede the rod/cone cells (with respect to the presentation to oncoming light ray/photon), there exists high oxygen demand in retina, copious ROS are detected in functional retina, NAD(P)H/reductase is involved in the cycle, events occur at sub-micrometer dimensioned phospholipid disks stacked to stabilize DROS and minimize free protons (quite like the thylakoids that harbor carotenoids in chloroplasts and cyanobacteria), etc. In the new scheme, photo-electric activation leads to charge separation and hyperpolarization. This electro-chemical signaling serves is the front-runner to a trigger for action potential relay along a neuron and the superoxide mediated phosphorylation of GDP bound to transducin serves as the initiator of signal transduction cascade. The newly proposed scheme allows a facile electrical connectivity of the retina-photoreceptors with the brain via the optic nerve, and is anatomically correlated with the structure and resolution or retina, and is kinetically viable.

Liposomes: Novel Drug Delivery Approach for Targeting Parkinson’s Disease

2020 ◽  
Vol 26 (37) ◽  
pp. 4721-4737 ◽  
Author(s):  
Bhumika Kumar ◽  
Mukesh Pandey ◽  
Faheem H. Pottoo ◽  
Faizana Fayaz ◽  
Anjali Sharma ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Drug Delivery ◽  
Parkinson's Disease ◽  
Side Effects ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Brain Targeting ◽  
Neural Cells ◽  
Blood Brain ◽  
The Brain

Parkinson’s disease is one of the most severe progressive neurodegenerative disorders, having a mortifying effect on the health of millions of people around the globe. The neural cells producing dopamine in the substantia nigra of the brain die out. This leads to symptoms like hypokinesia, rigidity, bradykinesia, and rest tremor. Parkinsonism cannot be cured, but the symptoms can be reduced with the intervention of medicinal drugs, surgical treatments, and physical therapies. Delivering drugs to the brain for treating Parkinson’s disease is very challenging. The blood-brain barrier acts as a highly selective semi-permeable barrier, which refrains the drug from reaching the brain. Conventional drug delivery systems used for Parkinson’s disease do not readily cross the blood barrier and further lead to several side-effects. Recent advancements in drug delivery technologies have facilitated drug delivery to the brain without flooding the bloodstream and by directly targeting the neurons. In the era of Nanotherapeutics, liposomes are an efficient drug delivery option for brain targeting. Liposomes facilitate the passage of drugs across the blood-brain barrier, enhances the efficacy of the drugs, and minimize the side effects related to it. The review aims at providing a broad updated view of the liposomes, which can be used for targeting Parkinson’s disease.

scholarly journals The manifold actions of the protein inhibitor of activated STAT proteins on the transcriptional activity of mineralocorticoid and glucocorticoid receptors in neural cells

2004 ◽  
Vol 32 (3) ◽  
pp. 825-841 ◽  
Author(s):  
M Tirard ◽  
J Jasbinsek ◽  
OF Almeida ◽  
TM Michaelidis
Keyword(s):  
Transcriptional Activity ◽  
Glucocorticoid Receptors ◽  
Specific Interaction ◽  
Human Neuroblastoma Cell ◽  
Physical Interaction ◽  
Neural Cells ◽  
Protein Inhibitor ◽  
Human Neuroblastoma ◽  
The Brain ◽  
Two Hybrid

Corticosteroid actions in the brain are exerted via the mineralocorticoid receptor (MR) and glucocorticoid receptor (GR). These receptors share several structural and functional similarities but their activation in the brain triggers distinct biological actions, for instance on neuronal survival or the regulation of the hypothalamo-pituitary-adrenal axis. Like other hormone-activated receptors, the transcriptional properties of the MR and GR depend on their ability to recruit a variety of co-regulators, which modulate their activity on target promoters, in a specific manner. The N-terminal regions of the MR and GR share the smallest degree of sequence conservation, whereas they display opposite effects on the transactivation properties of these receptors; thus, they may provide surfaces suitable for receptorspecific interactions with co-regulatory proteins. Here, we employed a yeast two-hybrid system to identify molecules interacting with the N-terminal part of the MR (amino acids 170-433). This approach resulted in the isolation of representative cDNAs from all members of the protein inhibitor of activated STAT (PIAS) family of proteins as potential MR-interacting partners. In neural cells, PIAS3 exhibited a strong and specific interaction with MR, but not GR, as indicated by mammalian two-hybrid assays and co-immunoprecipitation experiments in vivo. The interaction with MR was enhanced in the presence of aldosterone, an MR agonist, and was found to occur through a conserved, serine- and acidic amino acid residue-rich domain of PIAS3. To compare the modulatory properties of PIAS proteins on MR and GR transcriptional activity in a neural environment, MMTV reporter gene assays were performed in the human neuroblastoma cell line SK-N-MC. This analysis revealed that PIAS3 can inhibit MR, but not GR, transactivation in response to their corresponding ligands. Further, it showed that PIAS1 and PIASxbeta, but not PIASy, could also inhibit MR-mediated transcription despite the lack of detected physical interaction with MR. Interestingly, PIASxbeta and PIASy dose-dependently co-activated GR, whereas PIAS1 impaired GR-induced transcription. Taken together the results reveal differential modulatory roles of the PIAS proteins on the transcriptional properties of MR and GR, thus providing new insights into the bifurcating actions of these two receptors in neural cells where they are frequently co-localized.

Perinatal Development of the Medial Nucleus of the Trapezoid Body

2018 ◽  
pp. 244-272
Author(s):  
Shobhana Sivaramakrishnan ◽  
Ashley Brandebura ◽  
Paul Holcomb ◽  
Daniel Heller ◽  
Douglas Kolson ◽  
...  
Keyword(s):  
Axon Guidance ◽  
Neural Circuit ◽  
Neural Cells ◽  
Calyx Of Held ◽  
Medial Nucleus ◽  
Target Neuron ◽  
Circuit Formation ◽  
Key Events ◽  
The Brain ◽  
Trapezoid Body

Bushy cells (BC) of the cochlear nucleus mono-innervate their target neuron, the principal cell of the medial nucleus of the trapezoid body (MNTB), via the calyx of Held (CH) terminal, which is a typically mammalian structure and perhaps the largest nerve terminal in the brain. CH:MNTB innervation has become an attractive model to study neural circuit formation because it forms quickly, passing through stages of competition in mice within 2–4 days. BCs innervate MNTB neurons by E17, but CHs do not begin to grow for another five days (P3). Progress has been made to identify molecular factors for axon guidance, CH growth, and physiological maturation of synaptic partners, but important details remain to be discovered. We summarize key events in CH formation and highlight unresolved issues in molecular and physiological signaling, roles for non-neural cells, and the nature of competition during the first postnatal week.

scholarly journals Retrotransposon-induced mosaicism in the neural genome

Open Biology ◽  
2018 ◽  
Vol 8 (7) ◽  
pp. 180074 ◽  
Author(s):  
Gabriela O. Bodea ◽  
Eleanor G. Z. McKelvey ◽  
Geoffrey J. Faulkner
Keyword(s):  
Brain Development ◽  
Adult Neurogenesis ◽  
Neurological Disease ◽  
Dynamic Structure ◽  
Neurological Function ◽  
Developing Brain ◽  
Neural Cells ◽  
The Past ◽  
Retrotransposon Activity ◽  
The Brain

Over the past decade, major discoveries in retrotransposon biology have depicted the neural genome as a dynamic structure during life. In particular, the retrotransposon LINE-1 (L1) has been shown to be transcribed and mobilized in the brain. Retrotransposition in the developing brain, as well as during adult neurogenesis, provides a milieu in which neural diversity can arise. Dysregulation of retrotransposon activity may also contribute to neurological disease. Here, we review recent reports of retrotransposon activity in the brain, and discuss the temporal nature of retrotransposition and its regulation in neural cells in response to stimuli. We also put forward hypotheses regarding the significance of retrotransposons for brain development and neurological function, and consider the potential implications of this phenomenon for neuropsychiatric and neurodegenerative conditions.

Comparison of mayfly (Ephemeroptera) taxocenes of permanent and intermittent Central European small streams via species traits

Biologia ◽  
2010 ◽  
Vol 65 (4) ◽  
Author(s):  
Pavla Řezníčková ◽  
Tomáš Soldán ◽  
Petr Pařil ◽  
Světlana Zahrádková
Keyword(s):  
Global Climate ◽  
Extreme Temperature ◽  
Oxygen Demand ◽  
Hydrological Regime ◽  
Species Traits ◽  
Individual Species ◽  
Biological Traits ◽  
Small Streams ◽  
High Oxygen Demand ◽  
The Impact

AbstractThe recurrent drying out of small streams in past decades has shown an urgent need to pay attention to the impact of global climate change. The objectives of this study were to describe the effect of drying out on the composition of the mayfly taxocene and evaluate the relevance of individual species traits for survival of mayflies to drying out. The mayfly taxocenes of two model localities, one at an intermittent and one at a permanent brook, were investigated in 2002, 2003 and 2005. Compared with the permanent stream, the taxocene of the intermittent stream was short of nine species, foremost rheobionts and high oxygen demand species. To explain further differences between both stream types in survival and recolonisation ability, 15 species traits were evaluated. These included so-called “ecological traits” (e.g., habitat and substrate range, density, distribution, current velocity adaptation) and “biological traits” connected with life cycle and larval/adult adaptations. Species showing the highest number of advantageous traits (with only exception of Electrogena sp. cf. ujhelyii — species of taxonomically unclear status) were able to successfully survive under the unfavourable conditions of the intermittent brook. Biological traits considered more important in many respects seem to be good predictors for assessing sensitivity to extreme temperature changes, hydrological regime fluctuations and the survival/recolonisation ability of species in exposed habitats.

scholarly journals PPAR Gamma and Viral Infections of the Brain

2021 ◽  
Vol 22 (16) ◽  
pp. 8876
Author(s):  
Pierre Layrolle ◽  
Pierre Payoux ◽  
Stéphane Chavanas
Keyword(s):  
Viral Infections ◽  
Ppar Gamma ◽  
Brain Parenchyma ◽  
Peroxisome Proliferator ◽  
Neural Cells ◽  
Peroxisome Proliferator Activated Receptor ◽  
Immunodeficiency Virus ◽  
Health And Disease ◽  
The Brain

Peroxisome Proliferator-Activated Receptor gamma (PPARγ) is a master regulator of metabolism, adipogenesis, inflammation and cell cycle, and it has been extensively studied in the brain in relation to inflammation or neurodegeneration. Little is known however about its role in viral infections of the brain parenchyma, although they represent the most frequent cause of encephalitis and are a major threat for the developing brain. Specific to viral infections is the ability to subvert signaling pathways of the host cell to ensure virus replication and spreading, as deleterious as the consequences may be for the host. In this respect, the pleiotropic role of PPARγ makes it a critical target of infection. This review aims to provide an update on the role of PPARγ in viral infections of the brain. Recent studies have highlighted the involvement of PPARγ in brain or neural cells infected by immunodeficiency virus 1, Zika virus, or human cytomegalovirus. They have provided a better understanding on PPARγ functions in the infected brain, and revealed that it can be a double-edged sword with respect to inflammation, viral replication, or neuronogenesis. They unraveled new roles of PPARγ in health and disease and could possibly help designing new therapeutic strategies.

scholarly journals Insights into kinetics, release, and behavioral effects of brain-targeted hybrid nanoparticles for cholesterol delivery in Huntington’s disease

2020 ◽  
Author(s):  
Giulia Birolini ◽  
Marta Valenza ◽  
Ilaria Ottonelli ◽  
Alice Passoni ◽  
Monica Favagrossa ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Neurodegenerative Disorder ◽  
Polymeric Nanoparticles ◽  
Cholesterol Biosynthesis ◽  
Hybrid Nanoparticles ◽  
Neural Cells ◽  
Peripheral Tissues ◽  
Brain Cholesterol ◽  
The Brain

AbstractSupplementing brain cholesterol is emerging as a potential treatment for Huntington’s disease (HD), a genetic neurodegenerative disorder characterized, among other abnormalities, by inefficient brain cholesterol biosynthesis. However, delivering cholesterol to the brain is challenging due to the bloodbrain barrier (BBB), which prevents it from reaching the striatum, especially, with therapeutically relevant doses.Here we describe the distribution, kinetics, release, and safety of novel hybrid polymeric nanoparticles made of PLGA and cholesterol which were modified with an heptapeptide (g7) for BBB transit (hybrid-g7-NPs-chol). We show that these NPs rapidly reach the brain and target neural cells. Moreover, deuterium-labeled cholesterol from hybrid-g7-NPs-chol is released in a controlled manner within the brain and accumulates over time, while being rapidly removed from peripheral tissues and plasma. We confirm that systemic and repeated injections of the new hybrid-g7-NPs-chol enhanced endogenous cholesterol biosynthesis, prevented cognitive decline, and ameliorated motor defects in HD animals, without any inflammatory reaction.In summary, this study provides insights about the benefits and safety of cholesterol delivery through advanced brain-permeable nanoparticles for HD treatment.

scholarly journals New Technologies of Motor Control and Rehabilitation

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Albertas Skurvydas
Keyword(s):  
Motor Control ◽  
New Technologies ◽  
Modern Science ◽  
Computational Approach ◽  
Neural Cells ◽  
Motor Rehabilitation ◽  
Principal Mechanism ◽  
Brain Stroke ◽  
Computational Paradigm ◽  
The Brain

Modern paradigms of motor control and rehabilitation are analyzed in the paper. Two main paradigms, i. e. computational approach and dynamical system approach are engaged in rivalry in motor control and learning research at present. From the standpoint of computational paradigm the principal mechanism of motor control and learning consists in the ability of the brain “to calculate” (acting as some kind of biological computer). According to the paradigm of dynamical systems the mechanism of motor control is time dependent. In other words, it can be different each time. The main principles of motor control and properties of movements are given considerable attention in the paper. Besides, modern methods of motor rehabilitation after stroke are emphasized in the paper. Fitting of neuroprosthesis and restoration of damaged neural cells are significant maiden steps in modern science. The scientists are engaged in search for: a) constraining such mechanism prosthesis that would submit to the efforts of human will and b) restoring neural cells damaged because of the brain stroke suffered.Keywords: motor control, rehabilitation, stroke.

Quantitative neurogenetics: applications in understanding disease

2021 ◽  
Author(s):  
Ali Afrasiabi ◽  
Jeremy T. Keane ◽  
Julian Ik-Tsen Heng ◽  
Elizabeth E. Palmer ◽  
Nigel H. Lovell ◽  
...  
Keyword(s):  
Gene Expression ◽  
Genetic Risk ◽  
Tissue Specificity ◽  
High Throughput Sequencing ◽  
Molecular Genetic ◽  
Brain Dysfunction ◽  
Neural Cells ◽  
Expression Index ◽  
The Central Nervous System ◽  
The Brain

Neurodevelopmental and neurodegenerative disorders (NNDs) are a group of conditions with a broad range of core and co-morbidities, associated with dysfunction of the central nervous system. Improvements in high throughput sequencing have led to the detection of putative risk genetic loci for NNDs, however, quantitative neurogenetic approaches need to be further developed in order to establish causality and underlying molecular genetic mechanisms of pathogenesis. Here, we discuss an approach for prioritizing the contribution of genetic risk loci to complex-NND pathogenesis by estimating the possible impacts of these loci on gene regulation. Furthermore, we highlight the use of a tissue-specificity gene expression index and the application of artificial intelligence (AI) to improve the interpretation of the role of genetic risk elements in NND pathogenesis. Given that NND symptoms are associated with brain dysfunction, risk loci with direct, causative actions would comprise genes with essential functions in neural cells that are highly expressed in the brain. Indeed, NND risk genes implicated in brain dysfunction are disproportionately enriched in the brain compared with other tissues, which we refer to as brain-specific expressed genes. In addition, the tissue-specificity gene expression index can be used as a handle to identify non-brain contexts that are involved in NND pathogenesis. Lastly, we discuss how using an AI approach provides the opportunity to integrate the biological impacts of risk loci to identify those putative combinations of causative relationships through which genetic factors contribute to NND pathogenesis.

Extracellular matrix in plasticity and epileptogenesis

2008 ◽  
Vol 4 (3) ◽  
pp. 235-247 ◽  
Author(s):  
Alexander Dityatev ◽  
Tommaso Fellin
Keyword(s):  
Extracellular Matrix ◽  
Developmental Plasticity ◽  
Mossy Fibers ◽  
Long Term Potentiation ◽  
Therapeutic Interventions ◽  
Neural Cells ◽  
Dependent Manner ◽  
Extracellular Proteases ◽  
Mature Brain ◽  
The Brain

Extracellular matrix (ECM) in the brain is composed of molecules synthesized and secreted by neurons and glial cells in a cell-type-specific and activity-dependent manner. During development, ECM plays crucial roles in proliferation, migration and differentiation of neural cells. In the mature brain, ECM undergoes a slow turnover and supports multiple physiological processes, while restraining structural plasticity. In the first part of this review, we discuss the contribution of ECM molecules to different forms of plasticity, including developmental plasticity in the cortex, long-term potentiation and depression in the hippocampus, homeostatic scaling of synaptic transmission and metaplasticity. In the second part, we focus on pathological changes associated with epileptogenic mutations in ECM-related molecules or caused by seizure-induced remodeling of ECM. The available data suggest that ECM components regulating physiological plasticity are also engaged in different aspects of epileptogenesis, such as dysregulation of excitatory and inhibitory neurotransmission, sprouting of mossy fibers, granule cell dispersion and gliosis. At the end, we discuss combinatorial approaches that might be used to counteract seizure-induced dysregulation of both ECM molecules and extracellular proteases. By restraining ECM modification and preserving the status quo in the brain, these treatments might prove to be valid therapeutic interventions to antagonize the progression of epileptogenesis.

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