scholarly journals Plasticity of the dopaminergic phenotype and of locomotion in larval zebrafish induced by changes in brain excitability during the embryonic period.

2021 ◽  
Author(s):  
Sandrine Bataille ◽  
Hadrien Jalaber ◽  
Ingrid Colin ◽  
Damien Rémy ◽  
Pierre Affaticati ◽  
...  
Keyword(s):  
Neurodevelopmental Disorders ◽  
Molecular Mechanisms ◽  
Neuronal Excitability ◽  
Biological Marker ◽  
Pharmacological Treatments ◽  
Embryonic Period ◽  
Neuronal Communication ◽  
Larval Zebrafish ◽  
Zebrafish Larvae ◽  
And Behavior

Neuronal communication starts before the establishment of the synapses with forms of neuronal excitability occurring during the embryonic period, we called here Embryonic Neuronal Excitability (ENE). ENE has been shown to modulate the correct unfolding of development transcriptional programs but the global consequences for the developing organisms are not all understood. Here we monitored calcium transients as a proxy for ENE in zebrafish to assess the efficacy of transient pharmacological treatments applied by balneation during the embryonic period to modulate ENE. We also report lasting effects of 24h treatments, performed at the end of the embryonic development, on morphology and behavior of larval zebrafish. The post-mitotic differentiation of the dopaminergic phenotype is modulated by ENE in the forebrain. The plasticity of the dopaminergic specification occurs within a stable population of vMAT2 immuno-reactive cells, hence identifying an unanticipated biological marker for this reserve pool. We also report an effect of ENE on locomotion several days after the end of the treatments. In particular, the increase of ENE from 2 to 3 dpf promoted an hyperlocomotion in 6dpf zebrafish larvae which is an endophenotype for Attention Deficit with Hyperactivity Disorders and schizophrenia in zebrafish. These results provide a convenient framework to identify environmental factors that could regulate ENE and to study further the molecular mechanisms linking ENE to the neurotransmitters specification, with clinical relevance for the pathogenesis of neurodevelopmental disorders.

scholarly journals Molecular Mechanisms of Oxytocin Signaling at the Synaptic Connection

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Jan Bakos ◽  
Annamaria Srancikova ◽  
Tomas Havranek ◽  
Zuzana Bacova
Keyword(s):  
Neurodevelopmental Disorders ◽  
Molecular Mechanisms ◽  
Neuronal Excitability ◽  
Molecular Level ◽  
Short Term ◽  
Oxytocin Receptors ◽  
Potential Therapeutic Intervention ◽  
Early Alteration

Aberrant regulation of oxytocin signaling is associated with the etiology of neurodevelopmental disorders. Synaptic dysfunctions in neurodevelopmental disorders are becoming increasingly known, and their pathogenic mechanisms could be a target of potential therapeutic intervention. Therefore, it is important to pay attention to the role of oxytocin and its receptor in synapse structure, function, and neuron connectivity. An early alteration in oxytocin signaling may disturb neuronal maturation and may have short-term and long-term pathological consequences. At the molecular level, neurodevelopmental disorders include alterations in cytoskeletal rearrangement and neuritogenesis resulting in a diversity of synaptopathies. The presence of oxytocin receptors in the presynaptic and postsynaptic membranes and the direct effects of oxytocin on neuronal excitability by regulating the activity of ion channels in the cell membrane implicate that alterations in oxytocin signaling could be involved in synaptopathies. The ability of oxytocin to modulate neurogenesis, synaptic plasticity, and certain parameters of cytoskeletal arrangement is discussed in the present review.

scholarly journals Dysregulation of Astrocyte–Neuronal Communication in Alzheimer’s Disease

2021 ◽  
Vol 22 (15) ◽  
pp. 7887
Author(s):  
Carmen Nanclares ◽  
Andres Mateo Baraibar ◽  
Alfonso Araque ◽  
Paulo Kofuji
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Synaptic Plasticity ◽  
Neuronal Excitability ◽  
Active Role ◽  
Ionic Homeostasis ◽  
Neuronal Communication ◽  
Structural Support

Recent studies implicate astrocytes in Alzheimer’s disease (AD); however, their role in pathogenesis is poorly understood. Astrocytes have well-established functions in supportive functions such as extracellular ionic homeostasis, structural support, and neurovascular coupling. However, emerging research on astrocytic function in the healthy brain also indicates their role in regulating synaptic plasticity and neuronal excitability via the release of neuroactive substances named gliotransmitters. Here, we review how this “active” role of astrocytes at synapses could contribute to synaptic and neuronal network dysfunction and cognitive impairment in AD.

scholarly journals Standardized Method for the Assessment of Behavioral Responses of Zebrafish Larvae

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 884
Author(s):  
Hideyuki Maeda ◽  
Noritoshi Fukushima ◽  
Akihiro Hasumi
Keyword(s):  
Early Stage ◽  
Scientific Evidence ◽  
Video Tracking ◽  
Abnormal Behavior ◽  
Laboratory Setting ◽  
Zebrafish Larvae ◽  
Experimental Systems ◽  
Standardized Method ◽  
Life Phenomena ◽  
And Behavior

Zebrafish are easy to breed in a laboratory setting as they are extremely fertile and produce dozens of eggs per set. Because zebrafish eggs and the skin of the early-stage larvae are transparent, their embryos and the hearts and muscles of their larvae can be easily observed. Multiple rapid analyses of heart rate and behavior can be performed on these larvae simultaneously, enabling investigation of the influence of neuroactive substances on abnormal behavior, death, and associated pathogenetic mechanisms. Zebrafish larvae are becoming increasingly popular among researchers and are used in laboratories worldwide to study various vertebrate life phenomena; more experimental systems using zebrafish will undoubtedly be developed in the future. However, based on the available literature, we believe that the conceptualization of a protocol based on scientific evidence is necessary to achieve standardization. We exposed zebrafish larvae at 6–7 days post-fertilization to 50 repeated light–dark stimuli at either 15-min or 5-min intervals. We measured the traveled distance and habituation time through a video tracking apparatus. The traveled distance stabilized after the 16th repetition when the zebrafish were exposed to light–dark stimuli at 15-min intervals and after the 5th repetition when exposed at 5-min intervals. Additionally, at 15-min intervals, the peak of the traveled distance was reached within the first minute in a dark environment, whereas at 5-min intervals, it did not reach the peak even after 5 min. The traveled distance was more stable at 5-min intervals of light/dark stimuli than at 15-min intervals. Therefore, if one acclimatizes zebrafish larvae for 1 h and collects data from the 5th repetition of light/dark stimuli at intervals of 5 min in the light/dark test, a stable traveled distance result can be obtained. The establishment of this standardized method would be beneficial for investigating substances of unknown lethal concentration.

Pharmacological mechanism of topiramate in the prophylaxis and treatment of migraine: a review

2018 ◽  
pp. 190-195
Author(s):  
Emanuela Paz Rosas ◽  
Raisa Ferreira Costa ◽  
Silvania Tavares Paz ◽  
Ana Paula Fernandes da Silva ◽  
Manuela Freitas Lyra de Freitas
Keyword(s):  
Cortical Spreading Depression ◽  
Molecular Mechanisms ◽  
Spreading Depression ◽  
Neuronal Excitability ◽  
Mechanisms Of Action ◽  
World Population ◽  
Gamma Aminobutyric Acid ◽  
Pharmacological Mechanism ◽  
Calcium Ion Channels ◽  
Voltage Dependent

Objective: This review sought to bring evidence of studies addressing the mechanisms of action of topiramate in the prevention and treatment of migraine. Background: Migraine is a neurovascular disorder that affects a large part of the world population. The use of prophylactics contributes to the decrease in the frequency and severity of this disease. Among the antiepileptic drugs, the topiramate, has proven to be the most effective for the treatment of migraine. Although the mechanism of action of this drug is still not well elucidated in the literature, there are several molecular mechanisms proposed. Methodology: A survey was carried out in the literature, from February to March 2018, in different databases, using the descriptors: topiramate, migraine and mechanisms of action. After a careful selection, 25 manuscripts were chosen for this review. Results: Evidence from a number of studies has indicated that the main mechanisms of action of topiramate are related to the modulation of voltage-dependent sodium and calcium ion channels, blockade of excitatory glutamate transmission and inhibition by gamma-aminobutyric acid receptors (GABA), AMPA/kainate and some isoenzymes of carbonic anhydrase. In addition, topiramate is involved in the suppression of cortical spreading depression, besides influencing trigeminovascular activity, and neuronal excitability. Conclusion: Thus, topiramate could be involved in the prevention of major events of the pathophysiology of migraine. Acting directly on cortical spreading depression (DAC), trigeminovascular signals and decreased central sensitization of migraine pain.

scholarly journals Fumonisin B1 Production by Fusarium Species and Mycotoxigenic Effect on Larval Zebrafish

2020 ◽  
Vol 31 (3) ◽  
pp. 91-107 ◽  
Author(s):  
Najihah Azman ◽  
Nur Ain Izzati Mohd Zainudin ◽  
Wan Norhamidah Wan Ibrahim
Keyword(s):  
Liquid Chromatography ◽  
Danio Rerio ◽  
Morphological Changes ◽  
Fusarium Species ◽  
Fumonisin B1 ◽  
Larval Zebrafish ◽  
Zebrafish Larvae ◽  
Significant Difference ◽  
Successful Amplification ◽  
Fast Liquid Chromatography

Fumonisin B1 (FB1) is a common mycotoxin produced by Fusarium species particularly F. proliferatum and F. verticillioides. The toxin produced can cause adverse effects on humans and animals. The objectives of this study were to detect the production of FB1 based on the amplification of FUM1 gene, to quantify FB1 produced by the isolates using Ultra-fast Liquid Chromatography (UFLC) analysis, to examine the embryotoxicity effect of FB1 and to determine EC50 toward the larvae of zebrafish (Danio rerio). Fifty isolates of Fusarium species were isolated from different hosts throughout Malaysia. Successful amplification of the FUM1 gene showed the presence of this gene (800 bp) in the genome of 48 out of 50 isolates. The highest level of FB1 produced by F. proliferatum isolate B2433 was 6677.32 ppm meanwhile F. verticillioides isolate J1363 was 954.01 ppm. From the assessment of embryotoxicity test of FB1 on larvae of zebrafish, five concentrations of FB1 (0.43 ppm, 0.58 ppm, 0.72 ppm, 0.87 ppm and 1.00 ppm) were tested. Morphological changes of the FB1 exposed-larvae were observed at 24 to 168 hpf. The mortality rate and abnormality of zebrafish larvae were significantly increased at 144 hpf exposure. Meanwhile, the spontaneous tail coiling showed a significant difference. There were no significant differences in the heartbeat rate. As a conclusion, the presence of FUM1 in every isolate can be detected by FUM1 gene analysis and both of the species produced different concentrations of FB1. This is the first report of FB1 produced by Fusarium species gave a significant effect on zebrafish development.

scholarly journals Remote Corticospinal Tract Degeneration After Cortical Stroke in Rats May Not Preclude Spontaneous Sensorimotor Recovery

2021 ◽  
pp. 154596832110413
Author(s):  
Michel R. T. Sinke ◽  
Geralda A. F. van Tilborg ◽  
Anu E. Meerwaldt ◽  
Caroline L. van Heijningen ◽  
Annette van der Toorn ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Corticospinal Tract ◽  
Sprague Dawley ◽  
Post Stroke ◽  
Neuronal Communication ◽  
Cortical Stroke ◽  
Magnetic Resonance Imaging Mri ◽  
And Behavior ◽  
Sensorimotor Recovery

Background. Recovery of motor function after stroke appears to be related to the integrity of axonal connections in the corticospinal tract (CST) and corpus callosum, which may both be affected after cortical stroke. Objective. In the present study, we aimed to elucidate the relationship of changes in measures of the CST and transcallosal tract integrity, with the interhemispheric functional connectivity and sensorimotor performance after experimental cortical stroke. Methods. We conducted in vivo diffusion magnetic resonance imaging (MRI), resting-state functional MRI, and behavior testing in twenty-five male Sprague Dawley rats recovering from unilateral photothrombotic stroke in the sensorimotor cortex. Twenty-three healthy rats served as controls. Results. A reduction in the number of reconstructed fibers, a lower fractional anisotropy, and higher radial diffusivity in the ipsilesional but intact CST, reflected remote white matter degeneration. In contrast, transcallosal tract integrity remained preserved. Functional connectivity between the ipsi- and contralesional forelimb regions of the primary somatosensory cortex significantly reduced at week 8 post-stroke. Comparably, usage of the stroke-affected forelimb was normal at week 28, following significant initial impairment between day 1 and week 8 post-stroke. Conclusions. Our study shows that post-stroke motor recovery is possible despite degeneration in the CST and may be supported by intact neuronal communication between hemispheres.

scholarly journals The Dynamic Modulation of GABAA Receptor Trafficking and Its Role in Regulating the Plasticity of Inhibitory Synapses

2011 ◽  
Vol 91 (3) ◽  
pp. 1009-1022 ◽  
Author(s):  
Mansi Vithlani ◽  
Miho Terunuma ◽  
Stephen J. Moss
Keyword(s):  
Neuronal Excitability ◽  
Tonic Inhibition ◽  
Inhibitory Synapses ◽  
General Anesthetics ◽  
Selective Stabilization ◽  
Neuronal Plasma Membrane ◽  
Sites Of Action ◽  
And Behavior ◽  
The Impact ◽  
The Brain

Inhibition in the adult mammalian central nervous system (CNS) is mediated by γ-aminobutyric acid (GABA). The fast inhibitory actions of GABA are mediated by GABA type A receptors (GABAARs); they mediate both phasic and tonic inhibition in the brain and are the principle sites of action for anticonvulsant, anxiolytic, and sedative-hypnotic agents that include benzodiazepines, barbiturates, neurosteroids, and some general anesthetics. GABAARs are heteropentameric ligand-gated ion channels that are found concentrated at inhibitory postsynaptic sites where they mediate phasic inhibition and at extrasynaptic sites where they mediate tonic inhibition. The efficacy of inhibition and thus neuronal excitability is critically dependent on the accumulation of specific GABAAR subtypes at inhibitory synapses. Here we evaluate how neurons control the number of GABAARs on the neuronal plasma membrane together with their selective stabilization at synaptic sites. We then go on to examine the impact that these processes have on the strength of synaptic inhibition and behavior.

TRPV4 activation at the physiological temperature is a critical determinant of neuronal excitability and behavior

2015 ◽  
Vol 467 (12) ◽  
pp. 2495-2507 ◽  
Author(s):  
Koji Shibasaki ◽  
Shouta Sugio ◽  
Keizo Takao ◽  
Akihiro Yamanaka ◽  
Tsuyoshi Miyakawa ◽  
...  
Keyword(s):  
Neuronal Excitability ◽  
Critical Determinant ◽  
Physiological Temperature ◽  
And Behavior

Prader-Willi Syndrome: Consensus Diagnostic Criteria

PEDIATRICS ◽  
1993 ◽  
Vol 91 (2) ◽  
pp. 398-402 ◽  
Author(s):  
Vanja A. Holm ◽  
Suzanne B. Cassidy ◽  
Merlin G. Butler ◽  
Jeanne M. Hanchett ◽  
Louise R. Greenswag ◽  
...  
Keyword(s):  
Diagnostic Criteria ◽  
Biological Marker ◽  
Scoring Systems ◽  
Clinical Findings ◽  
Laboratory Research ◽  
Prader Willi Syndrome ◽  
Research Activity ◽  
Behaviorally Disturbed ◽  
Adolescents And Adults ◽  
And Behavior

The diagnosis of Prader-Willi syndrome (PWS) is based on clinical findings that change with age. Hypotonia is prominent in infancy. Obesity, mild mental retardation or learning disability, and behavior problems, especially in association with food and eating result in a debilitating physical and developmental disability in adolescence and adulthood. No consistent biological marker is yet available for PWS in spite of recent research activity in cytogenetics and molecular genetics. Diagnostic criteria for PWS were developed by consensus of seven clinicians experienced with the syndrome in consultation with national and international experts. Two scoring systems are provided: one for children aged 0 to 36 months and another one for children aged 3 years to adults. These criteria will aid in recognition of the syndrome in hypotonic infants and in obese, mildly retarded, behaviorally disturbed adolescents and adults. They will also ensure uniform diagnosis for future clinical and laboratory research in PWS.

Play Therapy for Children With Neurodevelopmental Disorders

2019 ◽  
pp. 264-280
Author(s):  
Gaurav Thapliyal ◽  
Sushma Kotnala
Keyword(s):  
Play Therapy ◽  
Neurodevelopmental Disorders ◽  
Therapeutic Approaches ◽  
The World ◽  
Recent Trends ◽  
And Behavior

A play is referred to the language of children through which they express and communicate their feelings, thoughts, and behavior in a playful way. Play therapy enables children to gain an understanding of themselves and the world around them and helps them to overcome behavioral, emotional, social, and various other issues through play activities. The chapter majorly focuses on the effectiveness of play therapy in different neurodevelopmental disorders. Recent trends and studies suggested that play therapy is one of the most favored therapeutic approaches used in the children with various neurodevelopmental disorders.

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