The Experts below are selected from a list of 17250 Experts worldwide ranked by ideXlab platform

Mark F Mehler - One of the best experts on this subject based on the ideXlab platform.

  • understanding Neurological Disease Mechanisms in the era of epigenetics
    JAMA Neurology, 2013
    Co-Authors: Irfan A Qureshi, Mark F Mehler
    Abstract:

    The burgeoning field of epigenetics is making a significant impact on our understanding of brain evolution, development, and function. In fact, it is now clear that epigenetic Mechanisms promote seminal neurobiological processes, ranging from neural stem cell maintenance and differentiation to learning and memory. At the molecular level, epigenetic Mechanisms regulate the structure and activity of the genome in response to intracellular and environmental cues, including the deployment of cell type–specific gene networks and those underlying synaptic plasticity. Pharmacological and genetic manipulation of epigenetic factors can, in turn, induce remarkable changes in neural cell identity and cognitive and behavioral phenotypes. Not surprisingly, it is also becoming apparent that epigenetics is intimately involved in Neurological Disease pathogenesis. Herein, we highlight emerging paradigms for linking epigenetic machinery and processes with Neurological Disease states, including how (1) mutations in genes encoding epigenetic factors cause Disease, (2) genetic variation in genes encoding epigenetic factors modify Disease risk, (3) abnormalities in epigenetic factor expression, localization, or function are involved in Disease pathophysiology, (4) epigenetic Mechanisms regulate Disease-associated genomic loci, gene products, and cellular pathways, and (5) differential epigenetic profiles are present in patient-derived central and peripheral tissues.

Katie A Ferguson - One of the best experts on this subject based on the ideXlab platform.

  • modeling oscillatory dynamics in brain microcircuits as a way to help uncover Neurological Disease Mechanisms a proposal
    Chaos, 2013
    Co-Authors: Frances K Skinner, Katie A Ferguson
    Abstract:

    There is an undisputed need and requirement for theoretical and computational studies in Neuroscience today. Furthermore, it is clear that oscillatory dynamical output from brain networks is representative of various behavioural states, and it is becoming clear that one could consider these outputs as measures of normal and pathological brain states. Although mathematical modeling of oscillatory dynamics in the context of Neurological Disease exists, it is a highly challenging endeavour because of the many levels of organization in the nervous system. This challenge is coupled with the increasing knowledge of cellular specificity and network dysfunction that is associated with Disease. Recently, whole hippocampus in vitro preparations from control animals have been shown to spontaneously express oscillatory activities. In addition, when using preparations derived from animal models of Disease, these activities show particular alterations. These preparations present an opportunity to address challenges involved with using models to gain insight because of easier access to simultaneous cellular and network measurements, and pharmacological modulations. We propose that by developing and using models with direct links to experiment at multiple levels, which at least include cellular and microcircuit, a cycling can be set up and used to help us determine critical Mechanisms underlying Neurological Disease. We illustrate our proposal using our previously developed inhibitory network models in the context of these whole hippocampus preparations and show the importance of having direct links at multiple levels.

Irfan A Qureshi - One of the best experts on this subject based on the ideXlab platform.

  • understanding Neurological Disease Mechanisms in the era of epigenetics
    JAMA Neurology, 2013
    Co-Authors: Irfan A Qureshi, Mark F Mehler
    Abstract:

    The burgeoning field of epigenetics is making a significant impact on our understanding of brain evolution, development, and function. In fact, it is now clear that epigenetic Mechanisms promote seminal neurobiological processes, ranging from neural stem cell maintenance and differentiation to learning and memory. At the molecular level, epigenetic Mechanisms regulate the structure and activity of the genome in response to intracellular and environmental cues, including the deployment of cell type–specific gene networks and those underlying synaptic plasticity. Pharmacological and genetic manipulation of epigenetic factors can, in turn, induce remarkable changes in neural cell identity and cognitive and behavioral phenotypes. Not surprisingly, it is also becoming apparent that epigenetics is intimately involved in Neurological Disease pathogenesis. Herein, we highlight emerging paradigms for linking epigenetic machinery and processes with Neurological Disease states, including how (1) mutations in genes encoding epigenetic factors cause Disease, (2) genetic variation in genes encoding epigenetic factors modify Disease risk, (3) abnormalities in epigenetic factor expression, localization, or function are involved in Disease pathophysiology, (4) epigenetic Mechanisms regulate Disease-associated genomic loci, gene products, and cellular pathways, and (5) differential epigenetic profiles are present in patient-derived central and peripheral tissues.

Frances K Skinner - One of the best experts on this subject based on the ideXlab platform.

  • modeling oscillatory dynamics in brain microcircuits as a way to help uncover Neurological Disease Mechanisms a proposal
    Chaos, 2013
    Co-Authors: Frances K Skinner, Katie A Ferguson
    Abstract:

    There is an undisputed need and requirement for theoretical and computational studies in Neuroscience today. Furthermore, it is clear that oscillatory dynamical output from brain networks is representative of various behavioural states, and it is becoming clear that one could consider these outputs as measures of normal and pathological brain states. Although mathematical modeling of oscillatory dynamics in the context of Neurological Disease exists, it is a highly challenging endeavour because of the many levels of organization in the nervous system. This challenge is coupled with the increasing knowledge of cellular specificity and network dysfunction that is associated with Disease. Recently, whole hippocampus in vitro preparations from control animals have been shown to spontaneously express oscillatory activities. In addition, when using preparations derived from animal models of Disease, these activities show particular alterations. These preparations present an opportunity to address challenges involved with using models to gain insight because of easier access to simultaneous cellular and network measurements, and pharmacological modulations. We propose that by developing and using models with direct links to experiment at multiple levels, which at least include cellular and microcircuit, a cycling can be set up and used to help us determine critical Mechanisms underlying Neurological Disease. We illustrate our proposal using our previously developed inhibitory network models in the context of these whole hippocampus preparations and show the importance of having direct links at multiple levels.

Yoshiharu Murata - One of the best experts on this subject based on the ideXlab platform.

  • myosin va mutation in rats is an animal model for the human hereditary Neurological Disease griscelli syndrome type 1
    Annals of the New York Academy of Sciences, 2006
    Co-Authors: Yoshiko Takagishi, Yoshiharu Murata
    Abstract:

    A spontaneous Neurological mutation, dilute-opisthotonus (dop), was discovered in our breeding colony of Wistar rats. We found that the mutation affected the gene encoding Myosin Va (MyoVA), an actin-based molecular motor. Analysis of the myosin Va (Myo5a) gene of the dop genome showed the presence of a complex rearrangement consisting of a 306-bp inversion associated with 217-bp and 17-bp deletions. A 141-bp exon is skipped in the dop transcript, producing a dop cDNA with a 141 in-frame deletion in the sequences encoding the head region. Expression of the MyoVA protein is severely impaired in the brains of dop homozygous rats, suggesting they have a null mutation for Myo5a. In a morphological analysis of the cerebella of dop rats, we found an absence of smooth endoplasmic reticulum (SER) and of inositol 1,4,5-triphosphate (IP3) receptors in the dendritic spines of Purkinje cells (PC). The SER acts as an intracellular Ca(2+) store and IP3-mediated Ca(2+) signaling in dendritic spines plays a critical role in synaptic regulation. We therefore measured synaptic transmission and long-term depression (LTD), a form of synaptic plasticity underlying cerebellar motor learning, at PC synapses in the cerebella of dop rats. We found that synaptic transmission at the PC synapses is largely normal, whereas the LTD is deficient due to a decrease in IP3-mediated Ca(2+) release from the SER in the PC spines of the dop cerebella. These findings may account for the ataxic movements and clonic convulsions displayed by dop rats. They also contribute to our understanding of the Neurological Disease Mechanisms of the human hereditary Disease Griscelli syndrome type 1, which is caused by mutation of the Myo5a gene.