scholarly journals The Function of Sialidase Revealed by Sialidase Activity Imaging Probe

2021 ◽  
Vol 22 (6) ◽  
pp. 3187
Author(s):  
Akira Minami ◽  
Yuuki Kurebayashi ◽  
Tadanobu Takahashi ◽  
Tadamune Otsubo ◽  
Kiyoshi Ikeda ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Neural Circuit ◽  
Glutamate Release ◽  
Feedback Mechanism ◽  
Excitatory Neurotransmitter ◽  
Imaging Probe ◽  
Sialidase Activity ◽  
Mammalian Tissues ◽  
Neural Excitation ◽  
The Brain

Sialidase cleaves sialic acid residues from glycans such as glycoproteins and glycolipids. In the brain, desorption of the sialic acid by sialidase is essential for synaptic plasticity, learning and memory and synaptic transmission. BTP3-Neu5Ac has been developed for sensitive imaging of sialidase enzyme activity in mammalian tissues. Sialidase activity in the rat hippocampus detected with BTP3-Neu5Ac increases rapidly by neuronal depolarization. It is presumed that an increased sialidase activity in conjunction with neural excitation is involved in the formation of the neural circuit for memory. Since sialidase inhibits the exocytosis of the excitatory neurotransmitter glutamate, the increased sialidase activity by neural excitation might play a role in the negative feedback mechanism against the glutamate release. Mammalian tissues other than the brain have also been stained with BTP3-Neu5Ac. On the basis of information on the sialidase activity imaging in the pancreas, it was found that sialidase inhibitor can be used as an anti-diabetic drug that can avoid hypoglycemia, a serious side effect of insulin secretagogues. In this review, we discuss the role of sialidase in the brain as well as in the pancreas and skin, as revealed by using a sialidase activity imaging probe. We also present the detection of influenza virus with BTP3-Neu5Ac and modification of BTP3-Neu5Ac.

scholarly journals Multiplex imaging of quantal glutamate release and presynaptic Ca2+ at multiple synapses in situ

2018 ◽  
Author(s):  
Thomas P. Jensen ◽  
Kaiyu Zheng ◽  
Nicholas Cole ◽  
Jonathan S. Marvin ◽  
Loren L. Looger ◽  
...  
Keyword(s):  
Neural Circuit ◽  
Glutamate Release ◽  
Loose Coupling ◽  
Excitatory Neurotransmitter ◽  
Presynaptic Function ◽  
Brain Circuits ◽  
Presynaptic Boutons ◽  
Central Synapses ◽  
Nanomolar Range

AbstractInformation processing by brain circuits depends on Ca2+-dependent, stochastic release of the excitatory neurotransmitter glutamate. Optical glutamate sensors have enabled detection of evoked and spontaneous synaptic discharges. However, monitoring presynaptic function and its underpinning machinery in situ requires simultaneous readout of quantal glutamate release and nanomolar presynaptic Ca2+. Here, we find that the fluorescence lifetime of the red-shifted Ca2+ indicator Cal-590 is Ca2+-sensitive in the nanomolar range, and employ it in combination with green glutamate sensors to relate quantal neurotransmission to presynaptic Ca2+ kinetics. Imaging of multiple synapses in an identified neural circuit reveals that fluctuations both in spike-evoked Ca2+ transients and in resting presynaptic Ca2+ can affect release efficacy. At the sub-microscopic level within individual presynaptic boutons, we detected no consistent co-localisation of presynaptic Ca2+ entry and glutamate release sites, suggesting loose coupling between the two. The present approach broadens qualitatively our horizon in understanding release machinery of central synapses.

scholarly journals A Conditional Glutamatergic Synaptic Vesicle Marker for Drosophila

2022 ◽  
Author(s):  
Sarah J Certel ◽  
Evelyne Ruchti ◽  
Brian D McCabe ◽  
R Steven Stowers
Keyword(s):  
Nervous System ◽  
Synaptic Vesicles ◽  
Neural Circuit ◽  
Glutamate Release ◽  
Nervous System Development ◽  
Central Complex ◽  
Excitatory Neurotransmitter ◽  
Glutamatergic Neurons ◽  
Brain Functions ◽  
Conditional Expression

Abstract Glutamate is a principal neurotransmitter used extensively by the nervous systems of all vertebrate and invertebrate animals. It is primarily an excitatory neurotransmitter that has been implicated in nervous system development as well as a myriad of brain functions from the simple transmission of information between neurons to more complex aspects of nervous system function including synaptic plasticity, learning, and memory. Identification of glutamatergic neurons and their sites of glutamate release are thus essential for understanding the mechanisms of neural circuit function and how information is processed to generate behavior. Here we describe and characterize smFLAG-vGlut, a conditional marker of glutamatergic synaptic vesicles for the Drosophila model system. smFLAG-vGlut is validated for functionality, conditional expression, and specificity for glutamatergic neurons and synaptic vesicles. The utility of smFLAG-vGlut is demonstrated by glutamatergic neurotransmitter phenotyping of 26 different central complex neuron types of which nine were established to be glutamatergic. This illumination of glutamate neurotransmitter usage will enhance the modeling of central complex neural circuitry and thereby our understanding of information processing by this region of the fly brain. The use of smFLAG for glutamatergic neurotransmitter phenotyping and identification of glutamate release sites can be extended to any Drosophila neuron(s) represented by a binary transcription system driver.

scholarly journals Enhancement of elastin expression by transdermal administration of sialidase isozyme Neu2

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Akira Minami ◽  
Yuka Fujita ◽  
Jun Goto ◽  
Ayano Iuchi ◽  
Kosei Fujita ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Skin Diseases ◽  
Lower Layer ◽  
Elastic Fiber ◽  
Sialic Acid Residue ◽  
Elastic Fibers ◽  
Transdermal Administration ◽  
Sialidase Activity ◽  
Fiber Assembly ◽  
Senescence Accelerated Mice

AbstractReduction of elastin in the skin causes various skin diseases as well as wrinkles and sagging with aging. Sialidase is a hydrolase that cleaves a sialic acid residue from sialoglycoconjugate. Cleavage of sialic acid from microfibrils by the sialidase isozyme Neu1 facilitates elastic fiber assembly. In the present study, we showed that a lower layer of the dermis and muscle showed relatively intense sialidase activity. The sialidase activity in the skin decreased with aging. Choline and geranate (CAGE), one of the ionic liquids, can deliver the sialidase subcutaneously while maintaining the enzymatic activity. The elastin level in the dermis was increased by applying sialidase from Arthrobacter ureafaciens (AUSA) with CAGE on the skin for 5 days in rats and senescence-accelerated mice prone 1 and 8. Sialidase activity in the dermis was considered to be mainly due to Neu2 based on the expression level of sialidase isozyme mRNA. Transdermal administration of Neu2 with CAGE also increased the level of elastin in the dermis. Therefore, not only Neu1 but also Neu2 would be involved in elastic fiber assembly. Transdermal administration of sialidase is expected to be useful for improvement of wrinkles and skin disorders due to the loss of elastic fibers.

scholarly journals Synergistic Effect of Several Neurotransmitters in PFC-NAc-VTA Neural Circuit for the Anti-Depression Effect of Shuganheweitang in a Chronic Unpredictable Mild Stress Model

2021 ◽  
Vol 16 (3) ◽  
pp. 1934578X2110024
Author(s):  
Xin Chen ◽  
Yuanchun Ma ◽  
Xiongjun Mou ◽  
Hao Liu ◽  
Hao Ming ◽  
...  
Keyword(s):  
Animal Behavior ◽  
Neural Circuit ◽  
Concentration Level ◽  
Brain Regions ◽  
Mild Stress ◽  
Depression Effect ◽  
Monoamine Neurotransmitters ◽  
Reward Circuitry ◽  
High Doses ◽  
The Brain

Depression, a major worldwide mental disorder, leads to massive disability and can result in death. The PFC-NAc-VTA neuro circuit is related to emotional, neurovegetative, and cognitive functions, which emerge as a circuit-level framework for understanding reward deficits in depression. Neurotransmitters, which are widely distributed in different brain regions, are important detected targets for the evaluation of depression. Shuganheweitang (SGHWT) is a popular prescription in clinical therapy for depression. In order to investigate its possible pharmacodynamics and anti-depressive mechanism, the complex plant material was separated into different fractions. These in low and high doses, along with low and high doses of SGHWT were tested in animal behavior tests. The low and high doses of SGHWT were more effective than the various fractions, which indicate the importance of synergistic function in traditional Chinese medicine. Furthermore, amino acid (GABA, Glu) and monoamine neurotransmitters (DA, 5-HT, NA, 5-HIAA) in the PFC-NAc-VTA neuro circuit were investigated by UPLC-MS/MS. The level trend of DA and 5-HT were consistent in the PFC-NAc-VTA neuro circuit, whereas 5-HIAA was decreased in the PFC, Glu was decreased in the PFC and VTA, and NA and GABA were decreased in the NAc. The results indicate that the pathogenesis of depression is associated with dysfunction of the PFC-NAc-VTA neural circuit, mainly through the neural projection effects of neurotransmitters associated with various brain regions in the neural circuit. PCA and OPLS-DA score plots demonstrated the similarities of individuals within each group and the differences among the groups. In this study, SGHWT could regulate the concentration level of different neurotransmitters in the PFC-NAc-VTA neuro circuit to improve the depression, which benefitted from the recognition of the brain reward circuitry in mood disorders.

Sol-Gel Optical Sensors for Glutamate

2000 ◽  
Vol 662 ◽  
Author(s):  
Jenna L. Rickus ◽  
Esther Lan ◽  
Allan J. Tobin ◽  
Jeffery I. Zink ◽  
Bruce Dunn
Keyword(s):  
Optical Sensors ◽  
Sol Gel ◽  
Kinetic Studies ◽  
Excitatory Neurotransmitter ◽  
Nadh Fluorescence ◽  
Millisecond Time Scale ◽  
Temporal And Spatial ◽  
Sensor Detection ◽  
The Brain ◽  
Amino Acid Glutamate

AbstractThe amino acid glutamate is the major excitatory neurotransmitter used in the nervous system for interneuronal communication. It is used throughout the brain by various neuronal pathways including those involved in learning and memory, locomotion, and sensory perception. Because glutamate is released from neurons on a millisecond time scale into sub-micrometer spaces, the development of a glutamate biosensor with high temporal and spatial resolution is of great interest for the study of neurological function and disease. Here, we demonstrate the feasibility of an optical glutamate sensor based on the sol-gel encapsulation of the enzyme glutamate dehydrogenase (GDH). GDH catalyses the oxidative deamination of glutamate and the reduction of NAD+ to NADH. NADH fluorescence is the basis of the sensor detection. Thermodynamic and kinetic studies show that GDH remains active in the sol-gel matrix and that the reaction rate is correlated to the glutamate concentration.

Striatal dopamine mediates hallucination-like perception in mice

Science ◽  
2021 ◽  
Vol 372 (6537) ◽  
pp. eabf4740
Author(s):  
K. Schmack ◽  
M. Bosc ◽  
T. Ott ◽  
J. F. Sturgill ◽  
A. Kepecs
Keyword(s):  
Psychotic Disorders ◽  
Neural Circuit ◽  
Dopamine Neurons ◽  
Striatal Dopamine ◽  
Model Organisms ◽  
High Confidence ◽  
Optogenetic Stimulation ◽  
The Brain ◽  
Central Symptom ◽  
Stimulation Of

Hallucinations, a central symptom of psychotic disorders, are attributed to excessive dopamine in the brain. However, the neural circuit mechanisms by which dopamine produces hallucinations remain elusive, largely because hallucinations have been challenging to study in model organisms. We developed a task to quantify hallucination-like perception in mice. Hallucination-like percepts, defined as high-confidence false detections, increased after hallucination-related manipulations in mice and correlated with self-reported hallucinations in humans. Hallucination-like percepts were preceded by elevated striatal dopamine levels, could be induced by optogenetic stimulation of mesostriatal dopamine neurons, and could be reversed by the antipsychotic drug haloperidol. These findings reveal a causal role for dopamine-dependent striatal circuits in hallucination-like perception and open new avenues to develop circuit-based treatments for psychotic disorders.

scholarly journals Astrocytes: Heterogeneous and Dynamic Phenotypes in Neurodegeneration and Innate Immunity

2018 ◽  
Vol 25 (5) ◽  
pp. 455-474 ◽  
Author(s):  
Colm Cunningham ◽  
Aisling Dunne ◽  
Ana Belen Lopez-Rodriguez
Keyword(s):  
Neural Circuit ◽  
Phenotypic Diversity ◽  
Significant Heterogeneity ◽  
Therapeutic Implications ◽  
Numerous Cell ◽  
Health And Disease ◽  
The Subject ◽  
The Brain ◽  
Substantial Heterogeneity ◽  
Homogenous Population

Astrocytes are the most numerous cell type in the brain and perform several essential functions in supporting neuronal metabolism and actively participating in neural circuit and behavioral function. They also have essential roles as innate immune cells in responding to local neuropathology, and the manner in which they respond to brain injury and degeneration is the subject of increasing attention in neuroscience. Although activated astrocytes have long been thought of as a relatively homogenous population, which alter their phenotype in a relatively stereotyped way upon central nervous system injury, the last decade has revealed substantial heterogeneity in the basal state and significant heterogeneity of phenotype during reactive astrocytosis. Thus, phenotypic diversity occurs at two distinct levels: that determined by regionality and development and that determined by temporally dynamic changes to the environment of astrocytes during pathology. These inflammatory and pathological states shape the phenotype of these cells, with different consequences for destruction or recovery of the local tissue, and thus elucidating these phenotypic changes has significant therapeutic implications. In this review, we will focus on the phenotypic heterogeneity of astrocytes in health and disease and their propensity to change that phenotype upon subsequent stimuli.

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 THE VISUAL SYSTEM: A "CHICKEN AND EGG" PROBLEM SOLVED

2009 ◽  
Vol 05 (01) ◽  
pp. 115-121
Author(s):  
ANDREW R. PARKER ◽  
H. JOHN CAULFIELD
Keyword(s):  
Visual System ◽  
Neural Plasticity ◽  
Neural Circuit ◽  
Process Data ◽  
System A ◽  
New Information ◽  
The Brain

"What comes first: the chicken or the egg?" Eyes and vision were a great concern for Darwin. Recently, religious fundamentalists have started to attack evolution on the grounds that this is a chicken and egg problem. How could eyes improve without the brain module to use the new information that eye provides? But how could the brain evolve a neural circuit to process data not available to it until a new eye capability emerges? We argue that neural plasticity in the brain allows it to make use of essentially any useful information the eye can produce. And it does so easily within the animal's lifetime. Richard Gregory suggested something like this 40 years ago. Our work resolves a problem with his otherwise-insightful work.

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