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Carsten Saft - One of the best experts on this subject based on the ideXlab platform.

  • Laquinimod treatment in the R6/2 mouse model
    Scientific Reports, 2017
    Co-Authors: Gisa Ellrichmann, Liat Hayardeny, Alina Blusch, Oluwaseun Fatoba, Janine Brunner, Christiane Reick, Michael Hayden, Dominik Sehr, Konstanze F. Winklhofer, Carsten Saft
    Abstract:

    The transgenic mouse model R6/2 exhibits Huntington’s disease (HD)-like deficits and basic pathophysiological similarities. We also used the pheochromocytoma-12 (PC12)-Cell-Line-model to investigate the effect of laquinimod on metabolic activity. Laquinimod is an orally administered immunomodulatory substance currently under development for the treatment of multiple sclerosis (MS) and HD. As an essential effect, increased levels of BDNF were observed. Therefore, we investigated the therapeutic efficacy of laquinimod in the R6/2 model, focusing on its neuroprotective capacity. Weight course and survival were not influenced by laquinimod. Neither were any metabolic effects seen in an inducible PC12-Cell-Line model of HD. As a positive effect, motor functions of R6/2 mice at the age of 12 weeks significantly improved. Preservation of morphologically intact neurons was found after treatment in the striatum, as revealed by NeuN, DARPP-32, and ubiquitin. Biochemical analysis showed a significant increase in the brain-derived neurotrophic factor (BDNF) level in striatal but not in cortical neurons. The number of mutant huntingtin (mhtt) and inducible nitric oxide synthase (iNOS) positive Cells was reduced in both the striatum and motor cortex following treatment. These findings suggest that laquinimod could provide a mild effect on motor function and striatal histopathology, but not on survival. Besides influences on the immune system, influence on BDNF-dependent pathways in HD are discussed.

  • laquinimod treatment in the r6 2 mouse model
    Scientific Reports, 2017
    Co-Authors: Gisa Ellrichmann, Liat Hayardeny, Michael R Hayden, Alina Blusch, Oluwaseun Fatoba, Janine Brunner, Christiane Reick, Dominik Sehr, Konstanze F. Winklhofer, Carsten Saft
    Abstract:

    The transgenic mouse model R6/2 exhibits Huntington’s disease (HD)-like deficits and basic pathophysiological similarities. We also used the pheochromocytoma-12 (PC12)-Cell-Line-model to investigate the effect of laquinimod on metabolic activity. Laquinimod is an orally administered immunomodulatory substance currently under development for the treatment of multiple sclerosis (MS) and HD. As an essential effect, increased levels of BDNF were observed. Therefore, we investigated the therapeutic efficacy of laquinimod in the R6/2 model, focusing on its neuroprotective capacity. Weight course and survival were not influenced by laquinimod. Neither were any metabolic effects seen in an inducible PC12-Cell-Line model of HD. As a positive effect, motor functions of R6/2 mice at the age of 12 weeks significantly improved. Preservation of morphologically intact neurons was found after treatment in the striatum, as revealed by NeuN, DARPP-32, and ubiquitin. Biochemical analysis showed a significant increase in the brain-derived neurotrophic factor (BDNF) level in striatal but not in cortical neurons. The number of mutant huntingtin (mhtt) and inducible nitric oxide synthase (iNOS) positive Cells was reduced in both the striatum and motor cortex following treatment. These findings suggest that laquinimod could provide a mild effect on motor function and striatal histopathology, but not on survival. Besides influences on the immune system, influence on BDNF-dependent pathways in HD are discussed.

Gisa Ellrichmann - One of the best experts on this subject based on the ideXlab platform.

  • Laquinimod treatment in the R6/2 mouse model
    Scientific Reports, 2017
    Co-Authors: Gisa Ellrichmann, Liat Hayardeny, Alina Blusch, Oluwaseun Fatoba, Janine Brunner, Christiane Reick, Michael Hayden, Dominik Sehr, Konstanze F. Winklhofer, Carsten Saft
    Abstract:

    The transgenic mouse model R6/2 exhibits Huntington’s disease (HD)-like deficits and basic pathophysiological similarities. We also used the pheochromocytoma-12 (PC12)-Cell-Line-model to investigate the effect of laquinimod on metabolic activity. Laquinimod is an orally administered immunomodulatory substance currently under development for the treatment of multiple sclerosis (MS) and HD. As an essential effect, increased levels of BDNF were observed. Therefore, we investigated the therapeutic efficacy of laquinimod in the R6/2 model, focusing on its neuroprotective capacity. Weight course and survival were not influenced by laquinimod. Neither were any metabolic effects seen in an inducible PC12-Cell-Line model of HD. As a positive effect, motor functions of R6/2 mice at the age of 12 weeks significantly improved. Preservation of morphologically intact neurons was found after treatment in the striatum, as revealed by NeuN, DARPP-32, and ubiquitin. Biochemical analysis showed a significant increase in the brain-derived neurotrophic factor (BDNF) level in striatal but not in cortical neurons. The number of mutant huntingtin (mhtt) and inducible nitric oxide synthase (iNOS) positive Cells was reduced in both the striatum and motor cortex following treatment. These findings suggest that laquinimod could provide a mild effect on motor function and striatal histopathology, but not on survival. Besides influences on the immune system, influence on BDNF-dependent pathways in HD are discussed.

  • laquinimod treatment in the r6 2 mouse model
    Scientific Reports, 2017
    Co-Authors: Gisa Ellrichmann, Liat Hayardeny, Michael R Hayden, Alina Blusch, Oluwaseun Fatoba, Janine Brunner, Christiane Reick, Dominik Sehr, Konstanze F. Winklhofer, Carsten Saft
    Abstract:

    The transgenic mouse model R6/2 exhibits Huntington’s disease (HD)-like deficits and basic pathophysiological similarities. We also used the pheochromocytoma-12 (PC12)-Cell-Line-model to investigate the effect of laquinimod on metabolic activity. Laquinimod is an orally administered immunomodulatory substance currently under development for the treatment of multiple sclerosis (MS) and HD. As an essential effect, increased levels of BDNF were observed. Therefore, we investigated the therapeutic efficacy of laquinimod in the R6/2 model, focusing on its neuroprotective capacity. Weight course and survival were not influenced by laquinimod. Neither were any metabolic effects seen in an inducible PC12-Cell-Line model of HD. As a positive effect, motor functions of R6/2 mice at the age of 12 weeks significantly improved. Preservation of morphologically intact neurons was found after treatment in the striatum, as revealed by NeuN, DARPP-32, and ubiquitin. Biochemical analysis showed a significant increase in the brain-derived neurotrophic factor (BDNF) level in striatal but not in cortical neurons. The number of mutant huntingtin (mhtt) and inducible nitric oxide synthase (iNOS) positive Cells was reduced in both the striatum and motor cortex following treatment. These findings suggest that laquinimod could provide a mild effect on motor function and striatal histopathology, but not on survival. Besides influences on the immune system, influence on BDNF-dependent pathways in HD are discussed.

Riadh Ksouri - One of the best experts on this subject based on the ideXlab platform.

  • lc ms identification and preparative hplc isolation of frankenia pulverulenta phenolics with antioxidant and neuroprotective capacities in PC12 Cell Line
    Pharmaceutical Biology, 2017
    Co-Authors: Rim Ben Mansour, Megdiche Ksouri Wided, Stephanie Cluzet, Stephanie Krisa, Tristan Richard, Riadh Ksouri
    Abstract:

    AbstractContext: Frankenia pulverulenta L. (Frankeniaceae) is a medicinal species with carminative, analgesic and antiviral properties. However, phytochemical investigations, antioxidant and neuroprotective capacities of this plant remain unclear.Objective: This work assesses the phenolic composition of F. pulverulenta shoot and root and evaluates their antioxidant and neuroprotective capacities.Materials and methods: Successive fractionation of F. pulverulenta shoot and root using 6 solvents were used. Antioxidant capacity of these fractions was assessed through four in vitro tests (DPPH, ABTS, Fe-chelating activity and ORAC). Phenolic identification, purification as well as neuroprotective activity of ethyl acetate (EtOAc) fraction and purified molecules were assessed.Results: Among the tested fractions, EtOAc shoot and root fractions possessed considerable phenolic contents (383 and 374 mg GAE/g E, respectively) because of their important ORAC (821 and 1054 mg of TE/g E), DPPH (586 and 750 mg of TE/g) ...

  • LC-MS identification and preparative HPLC isolation of Frankenia pulverulenta phenolics with antioxidant and neuroprotective capacities in PC12 Cell Line
    Taylor & Francis Group, 2017
    Co-Authors: Rim Ben Mansour, Megdiche Ksouri Wided, Stephanie Cluzet, Stephanie Krisa, Tristan Richard, Riadh Ksouri
    Abstract:

    Context: Frankenia pulverulenta L. (Frankeniaceae) is a medicinal species with carminative, analgesic and antiviral properties. However, phytochemical investigations, antioxidant and neuroprotective capacities of this plant remain unclear. Objective: This work assesses the phenolic composition of F. pulverulenta shoot and root and evaluates their antioxidant and neuroprotective capacities. Materials and methods: Successive fractionation of F. pulverulenta shoot and root using 6 solvents were used. Antioxidant capacity of these fractions was assessed through four in vitro tests (DPPH, ABTS, Fe-chelating activity and ORAC). Phenolic identification, purification as well as neuroprotective activity of ethyl acetate (EtOAc) fraction and purified molecules were assessed. Results: Among the tested fractions, EtOAc shoot and root fractions possessed considerable phenolic contents (383 and 374 mg GAE/g E, respectively) because of their important ORAC (821 and 1054 mg of TE/g E), DPPH (586 and 750 mg of TE/g) and ABTS (1453 and 1319 mg of TE/g) results. Moreover, gallic acid, quercetin, quercetin galloyl glucoside, trigalloyl hexoside, procyanidin dimers and sulfated flavonoids were identified by LC-DAD-ESI-MS for the first time in this species. The relevant cytoprotective capacity (at 300 μg/mL) against β-amyloid peptide induced toxicity in PC12 Cells of EtOAc fractions were corroborated with the chemical composition. In addition, purified molecules were tested for their ORAC and neuroprotective activity. Quercetin showed the best ORAC value (33.55 mmol TE/g polyphenols); nevertheless, procyanidin dimer exhibited an exceptionally efficient neuroprotective activity (100% of viability at 50 μg/mL). Discussion and conclusions: These findings suggest that this halophyte is a promising source of antioxidant and neuroprotective molecules for pharmaceutical purposes

  • assessment of antioxidant activity and neuroprotective capacity on PC12 Cell Line of frankenia thymifolia and related phenolic lc ms ms identification
    Evidence-based Complementary and Alternative Medicine, 2016
    Co-Authors: Rim Ben Mansour, Stephanie Cluzet, Stephanie Krisa, Tristan Richard, Wided Megdiche Ksouri, Riadh Ksouri
    Abstract:

    This work aimed to investigate the richness of a Tunisian xerohalophyte Frankenia thymifolia aerial and root parts on phenolics and to evaluate the antioxidant and neuroprotective properties of this medicinal species. After fractionation using increasing and different solvent polarities, results displayed five fractions, where ethyl acetate (EtOAc) shoot and root fractions possess considerable total phenolic contents (221 and 308 mg of GAE/g of E, resp.) related to their important antioxidant activities such as ORAC (918 and 713 mg of TE/g of E), DPPH (282 and 821 mg of TE/g), and ABTS (778 and 1320 mg of TE/g) tests. Then, the identification of the main compounds by HPLC-DAD-ESI-MS and neuroprotective property of the most active fraction EtOAc were assessed. A total of 14 molecules were identified, which have been described for the first time in F. thymifolia. The major compounds identified were pinoresinol and kaempferol glycoside in aerial parts and gallic acid and ellagitannin in roots. Neuroprotective capacity against β-amyloid (Aβ) peptide induced toxicity in PC12 Cells of EtOAc fraction showed a significant protective activity at lower concentration (25 and 50 µM). The relevant antioxidant and neuroprotective activities of F. thymifolia EtOAc fraction corroborated their chemical compositions.

Konstanze F. Winklhofer - One of the best experts on this subject based on the ideXlab platform.

  • Laquinimod treatment in the R6/2 mouse model
    Scientific Reports, 2017
    Co-Authors: Gisa Ellrichmann, Liat Hayardeny, Alina Blusch, Oluwaseun Fatoba, Janine Brunner, Christiane Reick, Michael Hayden, Dominik Sehr, Konstanze F. Winklhofer, Carsten Saft
    Abstract:

    The transgenic mouse model R6/2 exhibits Huntington’s disease (HD)-like deficits and basic pathophysiological similarities. We also used the pheochromocytoma-12 (PC12)-Cell-Line-model to investigate the effect of laquinimod on metabolic activity. Laquinimod is an orally administered immunomodulatory substance currently under development for the treatment of multiple sclerosis (MS) and HD. As an essential effect, increased levels of BDNF were observed. Therefore, we investigated the therapeutic efficacy of laquinimod in the R6/2 model, focusing on its neuroprotective capacity. Weight course and survival were not influenced by laquinimod. Neither were any metabolic effects seen in an inducible PC12-Cell-Line model of HD. As a positive effect, motor functions of R6/2 mice at the age of 12 weeks significantly improved. Preservation of morphologically intact neurons was found after treatment in the striatum, as revealed by NeuN, DARPP-32, and ubiquitin. Biochemical analysis showed a significant increase in the brain-derived neurotrophic factor (BDNF) level in striatal but not in cortical neurons. The number of mutant huntingtin (mhtt) and inducible nitric oxide synthase (iNOS) positive Cells was reduced in both the striatum and motor cortex following treatment. These findings suggest that laquinimod could provide a mild effect on motor function and striatal histopathology, but not on survival. Besides influences on the immune system, influence on BDNF-dependent pathways in HD are discussed.

  • laquinimod treatment in the r6 2 mouse model
    Scientific Reports, 2017
    Co-Authors: Gisa Ellrichmann, Liat Hayardeny, Michael R Hayden, Alina Blusch, Oluwaseun Fatoba, Janine Brunner, Christiane Reick, Dominik Sehr, Konstanze F. Winklhofer, Carsten Saft
    Abstract:

    The transgenic mouse model R6/2 exhibits Huntington’s disease (HD)-like deficits and basic pathophysiological similarities. We also used the pheochromocytoma-12 (PC12)-Cell-Line-model to investigate the effect of laquinimod on metabolic activity. Laquinimod is an orally administered immunomodulatory substance currently under development for the treatment of multiple sclerosis (MS) and HD. As an essential effect, increased levels of BDNF were observed. Therefore, we investigated the therapeutic efficacy of laquinimod in the R6/2 model, focusing on its neuroprotective capacity. Weight course and survival were not influenced by laquinimod. Neither were any metabolic effects seen in an inducible PC12-Cell-Line model of HD. As a positive effect, motor functions of R6/2 mice at the age of 12 weeks significantly improved. Preservation of morphologically intact neurons was found after treatment in the striatum, as revealed by NeuN, DARPP-32, and ubiquitin. Biochemical analysis showed a significant increase in the brain-derived neurotrophic factor (BDNF) level in striatal but not in cortical neurons. The number of mutant huntingtin (mhtt) and inducible nitric oxide synthase (iNOS) positive Cells was reduced in both the striatum and motor cortex following treatment. These findings suggest that laquinimod could provide a mild effect on motor function and striatal histopathology, but not on survival. Besides influences on the immune system, influence on BDNF-dependent pathways in HD are discussed.

Liat Hayardeny - One of the best experts on this subject based on the ideXlab platform.

  • Laquinimod treatment in the R6/2 mouse model
    Scientific Reports, 2017
    Co-Authors: Gisa Ellrichmann, Liat Hayardeny, Alina Blusch, Oluwaseun Fatoba, Janine Brunner, Christiane Reick, Michael Hayden, Dominik Sehr, Konstanze F. Winklhofer, Carsten Saft
    Abstract:

    The transgenic mouse model R6/2 exhibits Huntington’s disease (HD)-like deficits and basic pathophysiological similarities. We also used the pheochromocytoma-12 (PC12)-Cell-Line-model to investigate the effect of laquinimod on metabolic activity. Laquinimod is an orally administered immunomodulatory substance currently under development for the treatment of multiple sclerosis (MS) and HD. As an essential effect, increased levels of BDNF were observed. Therefore, we investigated the therapeutic efficacy of laquinimod in the R6/2 model, focusing on its neuroprotective capacity. Weight course and survival were not influenced by laquinimod. Neither were any metabolic effects seen in an inducible PC12-Cell-Line model of HD. As a positive effect, motor functions of R6/2 mice at the age of 12 weeks significantly improved. Preservation of morphologically intact neurons was found after treatment in the striatum, as revealed by NeuN, DARPP-32, and ubiquitin. Biochemical analysis showed a significant increase in the brain-derived neurotrophic factor (BDNF) level in striatal but not in cortical neurons. The number of mutant huntingtin (mhtt) and inducible nitric oxide synthase (iNOS) positive Cells was reduced in both the striatum and motor cortex following treatment. These findings suggest that laquinimod could provide a mild effect on motor function and striatal histopathology, but not on survival. Besides influences on the immune system, influence on BDNF-dependent pathways in HD are discussed.

  • laquinimod treatment in the r6 2 mouse model
    Scientific Reports, 2017
    Co-Authors: Gisa Ellrichmann, Liat Hayardeny, Michael R Hayden, Alina Blusch, Oluwaseun Fatoba, Janine Brunner, Christiane Reick, Dominik Sehr, Konstanze F. Winklhofer, Carsten Saft
    Abstract:

    The transgenic mouse model R6/2 exhibits Huntington’s disease (HD)-like deficits and basic pathophysiological similarities. We also used the pheochromocytoma-12 (PC12)-Cell-Line-model to investigate the effect of laquinimod on metabolic activity. Laquinimod is an orally administered immunomodulatory substance currently under development for the treatment of multiple sclerosis (MS) and HD. As an essential effect, increased levels of BDNF were observed. Therefore, we investigated the therapeutic efficacy of laquinimod in the R6/2 model, focusing on its neuroprotective capacity. Weight course and survival were not influenced by laquinimod. Neither were any metabolic effects seen in an inducible PC12-Cell-Line model of HD. As a positive effect, motor functions of R6/2 mice at the age of 12 weeks significantly improved. Preservation of morphologically intact neurons was found after treatment in the striatum, as revealed by NeuN, DARPP-32, and ubiquitin. Biochemical analysis showed a significant increase in the brain-derived neurotrophic factor (BDNF) level in striatal but not in cortical neurons. The number of mutant huntingtin (mhtt) and inducible nitric oxide synthase (iNOS) positive Cells was reduced in both the striatum and motor cortex following treatment. These findings suggest that laquinimod could provide a mild effect on motor function and striatal histopathology, but not on survival. Besides influences on the immune system, influence on BDNF-dependent pathways in HD are discussed.