scholarly journals GABAergic Neuronal Precursor Grafting: Implications in Brain Regeneration and Plasticity

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Manuel Alvarez Dolado ◽  
Vania Broccoli
Keyword(s):  
Neurological Disorders ◽  
Normal Function ◽  
Inhibitory Neurons ◽  
Synaptic Connections ◽  
Cell Type Specificity ◽  
Brain Regeneration ◽  
Associated Functions ◽  
Promising Treatment ◽  
Neuronal Transplantation ◽  
Near Future

Numerous neurological disorders are caused by a dysfunction of the GABAergic system that impairs or either stimulates its inhibitory action over its neuronal targets. Pharmacological drugs have generally been proved very effective in restoring its normal function, but their lack of any sort of spatial or cell type specificity has created some limitations in their use. In the last decades, cell-based therapies using GABAergic neuronal grafts have emerged as a promising treatment, since they may restore the lost equilibrium by cellular replacement of the missing/altered inhibitory neurons or modulating the hyperactive excitatory system. In particular, the discovery that embryonic ganglionic eminence-derived GABAergic precursors are able to disperse and integrate in large areas of the host tissue after grafting has provided a strong rationale for exploiting their use for the treatment of diseased brains. GABAergic neuronal transplantation not only is efficacious to restore normal GABAergic activities but can also trigger or sustain high neuronal plasticity by promoting the general reorganization of local neuronal circuits adding new synaptic connections. These results cast new light on dynamics and plasticity of adult neuronal assemblies and their associated functions disclosing new therapeutic opportunities for the near future.

Importance of Zebrafish as an efficient research model for the screening of novel therapeutics in neurological disorders

2020 ◽  
Vol 19 ◽  
Author(s):  
Diksha Saluja ◽  
Rishabh Jhanji ◽  
Swati Kaushal ◽  
Bharti Verma ◽  
Neelam Sharma ◽  
...  
Keyword(s):  
Animal Model ◽  
Neurological Disorders ◽  
Tropical Fish ◽  
Mammalian Brain ◽  
Behavioral Repertoire ◽  
Experimental Procedure ◽  
Novel Drugs ◽  
Associated Functions ◽  
Pharmacology And Toxicology ◽  
Rats And Mice

Abstract:: In the previous years of research, the use of animal model becomes very common for the screening of novel drugs. Animal model represents the complex problems of humans into simplest forms which can be extended further to include the experimental procedure. The most successful models in neuroscience, rats and mice, undoubtedly considered as one of the best models to understand the psychology of mammalian brain and its associated functions involved in various behavioral repertoire. Moreover, recently researchers in behavioral neuroscience are focusing more on the use of aquatic animals especially fish as model species due to their simplicity, and cost effectiveness. Zebrafish (Danio rerio) is a tropical fish from minnow family a genetic structure surprisingly 84 % similar to humans. It is gaining popularity as a model to study the mechanism in behavioral neuropharmacology. Moreover, Zebrafish is having numerous advantages over other rodent models like ease in maintenance due to their small size; breeding power is more, transparency of embryos, overall reduced cost of experimentation and many more. Nowadays, it is considered as an ideal model to study the neurobehavioral aspects with relevance to humans. It is also used in varieties of scientific studies like genetics, neuroscience, pharmacology, and toxicology. In this manuscript, we have described the feasibility and importance of Zebrafish as a model for the screening of novel drugs for different neurological disorders.

Mutual Inhibition with Few Inhibitory Cells via Nonlinear Inhibitory Synaptic Interaction

2019 ◽  
Vol 31 (11) ◽  
pp. 2252-2265
Author(s):  
Felix Weissenberger ◽  
Marcelo Matheus Gauy ◽  
Xun Zou ◽  
Angelika Steger
Keyword(s):  
Neural Network ◽  
Nonlinear Interaction ◽  
Network Models ◽  
Inhibitory Neurons ◽  
Inhibitory Synapses ◽  
Synaptic Connections ◽  
Mutual Inhibition ◽  
Neural Network Models ◽  
Excitatory Neurons ◽  
Inhibitory Population

In computational neural network models, neurons are usually allowed to excite some and inhibit other neurons, depending on the weight of their synaptic connections. The traditional way to transform such networks into networks that obey Dale's law (i.e., a neuron can either excite or inhibit) is to accompany each excitatory neuron with an inhibitory one through which inhibitory signals are mediated. However, this requires an equal number of excitatory and inhibitory neurons, whereas a realistic number of inhibitory neurons is much smaller. In this letter, we propose a model of nonlinear interaction of inhibitory synapses on dendritic compartments of excitatory neurons that allows the excitatory neurons to mediate inhibitory signals through a subset of the inhibitory population. With this construction, the number of required inhibitory neurons can be reduced tremendously.

Modified Zipper Method: A Promising Treatment Option in Severe Pediatric Cases of Immune-Mediated Neurological Disorders

2021 ◽  
Author(s):  
Marc Nikolaus ◽  
Fabienne Kuehne ◽  
Anna Tietze ◽  
Ellen Knierim ◽  
Alexander Gratopp ◽  
...  
Keyword(s):  
Treatment Option ◽  
Neurological Disorders ◽  
Immune Mediated ◽  
Promising Treatment

scholarly journals Cell type specificity of neurovascular coupling in cerebral cortex

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Hana Uhlirova ◽  
Kıvılcım Kılıç ◽  
Peifang Tian ◽  
Martin Thunemann ◽  
Michèle Desjardins ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Blood Oxygenation ◽  
Inhibitory Neurons ◽  
Cell Type Specificity ◽  
Potential Therapeutic Target ◽  
Optogenetic Stimulation ◽  
Oxygenation Level ◽  
Cortical Excitation ◽  
Y1 Receptors ◽  
Cerebrovascular Regulation

Identification of the cellular players and molecular messengers that communicate neuronal activity to the vasculature driving cerebral hemodynamics is important for (1) the basic understanding of cerebrovascular regulation and (2) interpretation of functional Magnetic Resonance Imaging (fMRI) signals. Using a combination of optogenetic stimulation and 2-photon imaging in mice, we demonstrate that selective activation of cortical excitation and inhibition elicits distinct vascular responses and identify the vasoconstrictive mechanism as Neuropeptide Y (NPY) acting on Y1 receptors. The latter implies that task-related negative Blood Oxygenation Level Dependent (BOLD) fMRI signals in the cerebral cortex under normal physiological conditions may be mainly driven by the NPY-positive inhibitory neurons. Further, the NPY-Y1 pathway may offer a potential therapeutic target in cerebrovascular disease.

scholarly journals A Sex Perspective in Neurodegenerative Diseases: microRNAs as Possible Peripheral Biomarkers

2021 ◽  
Vol 22 (9) ◽  
pp. 4423
Author(s):  
Paola Piscopo ◽  
Maria Bellenghi ◽  
Valeria Manzini ◽  
Alessio Crestini ◽  
Giada Pontecorvi ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Neurological Disorders ◽  
Significant Variable ◽  
Patient Stratification ◽  
Literature Analysis ◽  
Therapeutic Approaches ◽  
Males And Females ◽  
Near Future ◽  
Future Patient ◽  
Lateral Sclerosis

Sex is a significant variable in the prevalence and incidence of neurological disorders. Sex differences exist in neurodegenerative disorders (NDs), where sex dimorphisms play important roles in the development and progression of Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. In the last few years, some sex specific biomarkers for the identification of NDs have been described and recent studies have suggested that microRNA (miRNA) could be included among these, as influenced by the hormonal and genetic background. Failing to consider the possible differences between males and females in miRNA evaluation could introduce a sex bias in studies by not considering some of these sex-related biomarkers. In this review, we recapitulate what is known about the sex-specific differences in peripheral miRNA levels in neurodegenerative diseases. Several studies have reported sex-linked disparities, and from the literature analysis miR-206 particularly has been shown to have a sex-specific involvement. Hopefully, in the near future, patient stratification will provide important additional clues in diagnosis, prognosis, and tailoring of the best therapeutic approaches for each patient. Sex-specific biomarkers, such as miRNAs, could represent a useful tool for characterizing subgroups of patients.

scholarly journals Manipulations of MeCP2 in glutamatergic neurons highlight their contributions to Rett and other neurological disorders

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Xiangling Meng ◽  
Wei Wang ◽  
Hui Lu ◽  
Ling-jie He ◽  
Wu Chen ◽  
...  
Keyword(s):  
Mouse Models ◽  
Neurological Disorders ◽  
Acoustic Startle ◽  
Acoustic Startle Response ◽  
Autism Spectrum ◽  
Inhibitory Neurons ◽  
Loss Of Function ◽  
Glutamatergic Neurons ◽  
Excitatory Neurotransmission ◽  
Spectrum Disorders

Many postnatal onset neurological disorders such as autism spectrum disorders (ASDs) and intellectual disability are thought to arise largely from disruption of excitatory/inhibitory homeostasis. Although mouse models of Rett syndrome (RTT), a postnatal neurological disorder caused by loss-of-function mutations in MECP2, display impaired excitatory neurotransmission, the RTT phenotype can be largely reproduced in mice simply by removing MeCP2 from inhibitory GABAergic neurons. To determine what role excitatory signaling impairment might play in RTT pathogenesis, we generated conditional mouse models with Mecp2 either removed from or expressed solely in glutamatergic neurons. MeCP2 deficiency in glutamatergic neurons leads to early lethality, obesity, tremor, altered anxiety-like behaviors, and impaired acoustic startle response, which is distinct from the phenotype of mice lacking MeCP2 only in inhibitory neurons. These findings reveal a role for excitatory signaling impairment in specific neurobehavioral abnormalities shared by RTT and other postnatal neurological disorders.

scholarly journals Modulation of synchronous gamma rhythm clusters

2019 ◽  
pp. 185-188 ◽  
Author(s):  
Denis Zakharov ◽  
Martin Krupa ◽  
Victor Tyutin ◽  
Boris Gutkin
Keyword(s):  
Sensory Processing ◽  
Neural Circuits ◽  
Cluster Structure ◽  
Pyramidal Cells ◽  
Inhibitory Neurons ◽  
Cluster Synchronization ◽  
Synaptic Connections ◽  
Frequency Adaptation ◽  
Gamma Rhythm ◽  
Interacting Populations

Gamma rhythm plays a key role in a number of cognitive tasks: working memory, sensory processing and routing of information across neural circuits. In comparison with other (lower frequency) oscillations it is sparser and heterogeneous in space. One way to model such properties of gamma rhythm is to describe it through a neural network consisting of interacting populations of pyramidal cells (excitatory neurons) and interneurons (inhibitory neurons), demonstrating cluster synchronization. The structure of such clusters can be modulated by endogenous neuromodulators: dopamine, acetylcholine, adrenaline, etc. In this article we consider the reconfiguring of synchronous clusters of pyramidal interneuron gamma rhythm (pyramidal interneuron gamma, PING) due to the variation of the frequency adaptation parameter of pyramidal cells and the strength of excitatory synaptic connections. We have shown that the variation of the frequency adaptation parameter has the strongest impact on the strongest influence on the cluster structure and can lead to either an increase or a decrease of the number of synchronous clusters.

Synaptic Connectivity in Cultured Hypothalamic Neuronal Networks

1997 ◽  
Vol 77 (6) ◽  
pp. 3218-3225 ◽  
Author(s):  
Thomas H. Müller ◽  
D. Swandulla ◽  
H. U. Zeilhofer
Keyword(s):  
Neuronal Networks ◽  
Network Formation ◽  
Inhibitory Neurons ◽  
Synaptic Connectivity ◽  
Synaptic Connections ◽  
Cellular Mechanisms ◽  
Patch Clamp Technique ◽  
Novel Approach

Müller, Thomas H., D. Swandulla, and H. U. Zeilhofer. Synaptic connectivity in cultured hypothalamic neuronal networks. J. Neurophysiol. 77: 3218–3225, 1997. We have developed a novel approach to analyze the synaptic connectivity of spontaneously active networks of hypothalamic neurons in culture. Synaptic connections were identified by recording simultaneously from pairs of neurons using the whole cell configuration of the patch-clamp technique and testing for evoked postsynaptic current responses to electrical stimulation of one of the neurons. Excitatory and inhibitory responses were distinguished on the basis of their voltage and time dependence. The distribution of latencies between presynaptic stimulation and postsynaptic response showed multiple peaks at regular intervals, suggesting that responses via both monosynaptic and polysynaptic paths were recorded. The probability that an excitatory event is transmitted to another excitatory neuron and results in an above-threshold stimulation was found to be only one in three to four. This low value indicates that in addition to evoked synaptic responses other sources of excitatory drive must contribute to the spontaneous activity observed in these networks. The various types of synaptic connections (excitatory and inhibitory, monosynaptic, and polysynaptic) were counted, and the observations analyzed using a probabilistic model of the network structure. This analysis provides estimates for the ratio of inhibitory to excitatory neurons in the network (1:1.5) and for the ratio of postsynaptic cells receiving input from a single GABAergic or glutamatergic neuron (3:1). The total number of inhibitory synaptic connections was twice that of excitatory connections. Cell pairs mutually connected by an excitatory and an inhibitory synapse occurred significantly more often than predicted by a random process. These results suggests that the formation of neuronal networks in vitro is controlled by cellular mechanisms that favor inhibitory connections in general and specifically enhance the formation of reciprocal connections between pairs of excitatory and inhibitory neurons. These mechanisms may contribute to network formation and function in vivo.

scholarly journals Through Predictive Personalized Medicine

2020 ◽  
Vol 10 (9) ◽  
pp. 594
Author(s):  
Giuseppe Giglia ◽  
Giuditta Gambino ◽  
Pierangelo Sardo
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Intracellular Signaling ◽  
Survival Rates ◽  
Therapeutic Outcomes ◽  
Programmed Cell Death 1 ◽  
Innovative Tool ◽  
Promising Treatment ◽  
Therapeutic Protocols ◽  
Near Future

Neuroblastoma (NBM) is a deadly form of solid tumor mostly observed in the pediatric age. Although survival rates largely differ depending on host factors and tumor-related features, treatment for clinically aggressive forms of NBM remains challenging. Scientific advances are paving the way to improved and safer therapeutic protocols, and immunotherapy is quickly rising as a promising treatment that is potentially safer and complementary to traditionally adopted surgical procedures, chemotherapy and radiotherapy. Improving therapeutic outcomes requires new approaches to be explored and validated. In-silico predictive models based on analysis of a plethora of data have been proposed by Lombardo et al. as an innovative tool for more efficacious immunotherapy against NBM. In particular, knowledge gained on intracellular signaling pathways linked to the development of NBM was used to predict how the different phenotypes could be modulated to respond to anti-programmed cell death-ligand-1 (PD-L1)/programmed cell death-1 (PD-1) immunotherapy. Prediction or forecasting are important targets of artificial intelligence and machine learning. Hopefully, similar systems could provide a reliable opportunity for a more targeted approach in the near future.

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