The Experts below are selected from a list of 522 Experts worldwide ranked by ideXlab platform

Nigel C Jones - One of the best experts on this subject based on the ideXlab platform.

  • environmental enrichment imparts disease modifying and transgenerational effects on Genetically Determined Epilepsy and anxiety
    Neurobiology of Disease, 2016
    Co-Authors: Gabi Dezsi, Ezgi Ozturk, Michael R Salzberg, Margaret J Morris, Terence J Obrien, Nigel C Jones
    Abstract:

    Abstract Introduction The absence epilepsies are presumed to be caused by genetic factors, but the influence of environmental exposures on Epilepsy development and severity, and whether this influence is transmitted to subsequent generations, is not well known. We assessed the effects of environmental enrichment on Epilepsy and anxiety outcomes in multiple generations of GAERS – a genetic rat model of absence Epilepsy that manifests comorbid elevated anxiety-like behaviour. Methods GAERS were exposed to environmental enrichment or standard housing beginning either prior to, or after Epilepsy onset, and underwent EEG recordings and anxiety testing. Then, we exposed male GAERS to early enrichment or standard housing and generated F1 progeny, which also underwent EEG recordings. Hippocampal CRH mRNA expression and DNA methylation were assessed using RT-PCR and pyrosequencing, respectively. Results Early environmental enrichment delayed the onset of Epilepsy in GAERS, and resulted in fewer seizures in adulthood, compared with standard housed GAERS. Enrichment also reduced the frequency of seizures when initiated in adulthood. Anxiety levels were reduced by enrichment, and these anti-epileptogenic and anxiolytic effects were heritable into the next generation. We also found reduced expression of CRH mRNA in GAERS exposed to enrichment, but this was not due to changes in DNA methylation. Conclusions Environmental enrichment produces disease-modifying effects on Genetically Determined absence Epilepsy and anxiety, and these beneficial effects are transferable to the subsequent generation. Reduced CRH expression was associated with these phenotypic improvements. Environmental stimulation holds promise as a naturalistic therapy for Genetically Determined Epilepsy which may benefit subsequent generations.

Massimo Mantegazza - One of the best experts on this subject based on the ideXlab platform.

  • a rescuable folding defective nav1 1 scn1a sodium channel mutant causes gefs common mechanism in nav1 1 related epilepsies
    Human Mutation, 2009
    Co-Authors: Raffaella Rusconi, Romina Combi, Sandrine Cestele, Daniele Grioni, Silvana Franceschetti, Leda Dalpra, Massimo Mantegazza
    Abstract:

    Mutations of voltage-gated Na+ channels are the most common known cause of Genetically Determined Epilepsy; Nav1.1 (SCN1A) is the most frequent target. They can cause both mild and severe forms, also in patients harboring the same mutation. We have recently characterized in a family with extreme phenotypes the first epileptogenic folding-defective Na+ channel mutant (Nav1.1-M1841T), whose loss of function is attenuated by interactions with associated proteins and drugs. We hypothesized that in vivo variability of the interactions may modulate the functional effect and thus the phenotype (Rusconi et al., 2007). Here we characterize another Nav1.1 folding-defective mutant (Nav1.1-R1916G) that, however, has been identified in a GEFS+ family with relatively mild phenotypes. This novel mutant shows a number of specific characteristics, but, similarly to Nav1.1-M1841T, it can be rescued by interactions with associated proteins and drugs. Thus, loss of function caused by folding defects that can be attenuated by molecular interactions may be a common pathogenic mechanism for Nav1.1 epileptogenic mutants. Folding defects can be present also in families showing only mild phenotypes in which, however, severe phenotypes could emerge within a permissive genetic background. © 2009 Wiley-Liss, Inc.

Gabi Dezsi - One of the best experts on this subject based on the ideXlab platform.

  • environmental enrichment imparts disease modifying and transgenerational effects on Genetically Determined Epilepsy and anxiety
    Neurobiology of Disease, 2016
    Co-Authors: Gabi Dezsi, Ezgi Ozturk, Michael R Salzberg, Margaret J Morris, Terence J Obrien, Nigel C Jones
    Abstract:

    Abstract Introduction The absence epilepsies are presumed to be caused by genetic factors, but the influence of environmental exposures on Epilepsy development and severity, and whether this influence is transmitted to subsequent generations, is not well known. We assessed the effects of environmental enrichment on Epilepsy and anxiety outcomes in multiple generations of GAERS – a genetic rat model of absence Epilepsy that manifests comorbid elevated anxiety-like behaviour. Methods GAERS were exposed to environmental enrichment or standard housing beginning either prior to, or after Epilepsy onset, and underwent EEG recordings and anxiety testing. Then, we exposed male GAERS to early enrichment or standard housing and generated F1 progeny, which also underwent EEG recordings. Hippocampal CRH mRNA expression and DNA methylation were assessed using RT-PCR and pyrosequencing, respectively. Results Early environmental enrichment delayed the onset of Epilepsy in GAERS, and resulted in fewer seizures in adulthood, compared with standard housed GAERS. Enrichment also reduced the frequency of seizures when initiated in adulthood. Anxiety levels were reduced by enrichment, and these anti-epileptogenic and anxiolytic effects were heritable into the next generation. We also found reduced expression of CRH mRNA in GAERS exposed to enrichment, but this was not due to changes in DNA methylation. Conclusions Environmental enrichment produces disease-modifying effects on Genetically Determined absence Epilepsy and anxiety, and these beneficial effects are transferable to the subsequent generation. Reduced CRH expression was associated with these phenotypic improvements. Environmental stimulation holds promise as a naturalistic therapy for Genetically Determined Epilepsy which may benefit subsequent generations.

Raffaella Rusconi - One of the best experts on this subject based on the ideXlab platform.

  • a rescuable folding defective nav1 1 scn1a sodium channel mutant causes gefs common mechanism in nav1 1 related epilepsies
    Human Mutation, 2009
    Co-Authors: Raffaella Rusconi, Romina Combi, Sandrine Cestele, Daniele Grioni, Silvana Franceschetti, Leda Dalpra, Massimo Mantegazza
    Abstract:

    Mutations of voltage-gated Na+ channels are the most common known cause of Genetically Determined Epilepsy; Nav1.1 (SCN1A) is the most frequent target. They can cause both mild and severe forms, also in patients harboring the same mutation. We have recently characterized in a family with extreme phenotypes the first epileptogenic folding-defective Na+ channel mutant (Nav1.1-M1841T), whose loss of function is attenuated by interactions with associated proteins and drugs. We hypothesized that in vivo variability of the interactions may modulate the functional effect and thus the phenotype (Rusconi et al., 2007). Here we characterize another Nav1.1 folding-defective mutant (Nav1.1-R1916G) that, however, has been identified in a GEFS+ family with relatively mild phenotypes. This novel mutant shows a number of specific characteristics, but, similarly to Nav1.1-M1841T, it can be rescued by interactions with associated proteins and drugs. Thus, loss of function caused by folding defects that can be attenuated by molecular interactions may be a common pathogenic mechanism for Nav1.1 epileptogenic mutants. Folding defects can be present also in families showing only mild phenotypes in which, however, severe phenotypes could emerge within a permissive genetic background. © 2009 Wiley-Liss, Inc.

Michael R Salzberg - One of the best experts on this subject based on the ideXlab platform.

  • environmental enrichment imparts disease modifying and transgenerational effects on Genetically Determined Epilepsy and anxiety
    Neurobiology of Disease, 2016
    Co-Authors: Gabi Dezsi, Ezgi Ozturk, Michael R Salzberg, Margaret J Morris, Terence J Obrien, Nigel C Jones
    Abstract:

    Abstract Introduction The absence epilepsies are presumed to be caused by genetic factors, but the influence of environmental exposures on Epilepsy development and severity, and whether this influence is transmitted to subsequent generations, is not well known. We assessed the effects of environmental enrichment on Epilepsy and anxiety outcomes in multiple generations of GAERS – a genetic rat model of absence Epilepsy that manifests comorbid elevated anxiety-like behaviour. Methods GAERS were exposed to environmental enrichment or standard housing beginning either prior to, or after Epilepsy onset, and underwent EEG recordings and anxiety testing. Then, we exposed male GAERS to early enrichment or standard housing and generated F1 progeny, which also underwent EEG recordings. Hippocampal CRH mRNA expression and DNA methylation were assessed using RT-PCR and pyrosequencing, respectively. Results Early environmental enrichment delayed the onset of Epilepsy in GAERS, and resulted in fewer seizures in adulthood, compared with standard housed GAERS. Enrichment also reduced the frequency of seizures when initiated in adulthood. Anxiety levels were reduced by enrichment, and these anti-epileptogenic and anxiolytic effects were heritable into the next generation. We also found reduced expression of CRH mRNA in GAERS exposed to enrichment, but this was not due to changes in DNA methylation. Conclusions Environmental enrichment produces disease-modifying effects on Genetically Determined absence Epilepsy and anxiety, and these beneficial effects are transferable to the subsequent generation. Reduced CRH expression was associated with these phenotypic improvements. Environmental stimulation holds promise as a naturalistic therapy for Genetically Determined Epilepsy which may benefit subsequent generations.