The Experts below are selected from a list of 315 Experts worldwide ranked by ideXlab platform

Daniel Paris - One of the best experts on this subject based on the ideXlab platform.

  • Acute or Delayed Treatment with Anatabine Improves Spatial Memory and Reduces Pathological Sequelae at Late Time-Points after Repetitive Mild Traumatic Brain Injury
    Journal of neurotrauma, 2017
    Co-Authors: Scott Ferguson, Daniel Paris, Michael Mullan, Laila Abdullah, Benoit Mouzon, Destinee Aponte, William Stewart, Fiona Crawford
    Abstract:

    Abstract Traumatic brain injury (TBI) has chronic and long-term consequences for which there are currently no approved pharmacological treatments. We have previously characterized the chronic neurobehavioral and pathological sequelae of a mouse model of repetitive mild TBI (r-mTBI) through to 2 years post-TBI. Despite the mild nature of the initial insult, secondary injury processes are initiated that involve neuroinflammatory and neurodegenerative pathways persisting and progressing for weeks and months post-injury and providing a potential window of opportunity for therapeutic intervention. In this study we examined the efficacy of a novel anti-inflammatory compound, Anatabine, in modifying outcome after TBI. Our model of r-mTBI involves a series of five mild impacts (midline impact at 5 m/sec, 1 mm strike depth, 200 msec dwell time) with an interval of 48 h. Anatabine treatment was administered starting 30 min after injury and was delivered continuously through drinking water. At 6 months after TBI, an...

  • Chronic Anatabine Treatment Reduces Alzheimer’s Disease (AD)-Like Pathology and Improves Socio-Behavioral Deficits in a Transgenic Mouse Model of AD
    PloS one, 2015
    Co-Authors: Megha Verma, David Beaulieu-abdelahad, Ghania Ait-ghezala, Fiona Crawford, Michael Mullan, Daniel Paris
    Abstract:

    Anatabine is a minor tobacco alkaloid, which is also found in plants of the Solanaceae family and displays a chemical structure similarity with nicotine. We have shown previously that Anatabine displays some anti-inflammatory properties and reduces microgliosis and tau phosphorylation in a pure mouse model of tauopathy. We therefore investigated the effects of a chronic oral treatment with Anatabine in a transgenic mouse model (Tg PS1/APPswe) of Alzheimer’s disease (AD) which displays pathological Aβ deposits, neuroinflammation and behavioral deficits. In the elevated plus maze, Tg PS1/APPswe mice exhibited hyperactivity and disinhibition compared to wild-type mice. Six and a half months of chronic oral Anatabine treatment, suppressed hyperactivity and disinhibition in Tg PS1/APPswe mice compared to Tg PS1/APPswe receiving regular drinking water. Tg PS1/APPswe mice also elicited profound social interaction and social memory deficits, which were both alleviated by the Anatabine treatment. We found that Anatabine reduces the activation of STAT3 and NFκB in the vicinity of Aβ deposits in Tg PS1/APPswe mice resulting in a reduction of the expression of some of their target genes including Bace1, iNOS and Cox-2. In addition, a significant reduction in microgliosis and pathological deposition of Aβ was observed in the brain of Tg PS1/APPswe mice treated with Anatabine. This is the first study to investigate the impact of chronic Anatabine treatment on AD-like pathology and behavior in a transgenic mouse model of AD. Overall, our data show that Anatabine reduces β-amyloidosis, neuroinflammation and alleviates some behavioral deficits in Tg PS1/APPswe, supporting further exploration of Anatabine as a possible disease modifying agent for the treatment of AD.

  • chronic Anatabine treatment reduces alzheimer s disease ad like pathology and improves socio behavioral deficits in a transgenic mouse model of ad
    PLOS ONE, 2015
    Co-Authors: Fiona Crawford, Michael Mullan, Megha Verma, David Beaulieuabdelahad, Ghania Aitghezala, Daniel Paris
    Abstract:

    Anatabine is a minor tobacco alkaloid, which is also found in plants of the Solanaceae family and displays a chemical structure similarity with nicotine. We have shown previously that Anatabine displays some anti-inflammatory properties and reduces microgliosis and tau phosphorylation in a pure mouse model of tauopathy. We therefore investigated the effects of a chronic oral treatment with Anatabine in a transgenic mouse model (Tg PS1/APPswe) of Alzheimer’s disease (AD) which displays pathological Aβ deposits, neuroinflammation and behavioral deficits. In the elevated plus maze, Tg PS1/APPswe mice exhibited hyperactivity and disinhibition compared to wild-type mice. Six and a half months of chronic oral Anatabine treatment, suppressed hyperactivity and disinhibition in Tg PS1/APPswe mice compared to Tg PS1/APPswe receiving regular drinking water. Tg PS1/APPswe mice also elicited profound social interaction and social memory deficits, which were both alleviated by the Anatabine treatment. We found that Anatabine reduces the activation of STAT3 and NFκB in the vicinity of Aβ deposits in Tg PS1/APPswe mice resulting in a reduction of the expression of some of their target genes including Bace1, iNOS and Cox-2. In addition, a significant reduction in microgliosis and pathological deposition of Aβ was observed in the brain of Tg PS1/APPswe mice treated with Anatabine. This is the first study to investigate the impact of chronic Anatabine treatment on AD-like pathology and behavior in a transgenic mouse model of AD. Overall, our data show that Anatabine reduces β-amyloidosis, neuroinflammation and alleviates some behavioral deficits in Tg PS1/APPswe, supporting further exploration of Anatabine as a possible disease modifying agent for the treatment of AD.

  • Anatabine reduces the amount of phosphorylated p65 NFκB immunopositive cells associated with β-amyloid deposits in the cortex of Tg PS1/APPswe mice.
    2015
    Co-Authors: Megha Verma, David Beaulieu-abdelahad, Ghania Ait-ghezala, Fiona Crawford, Michael Mullan, Daniel Paris
    Abstract:

    A) Representative 40X microscopic field revealing the presence of phosphorylated p65 NFκB immunopositive cells around Congo red stained β-amyloid deposits in the cortex of Tg PS1/APPswe mice receiving regular drinking water (placebo) or Anatabine at a dosage of 10 and 20 mg/Kg/Day in their drinking water. Data is presented as mean±SEM. B) The histogram represents the average amount of phospho p65 NFκB burden (expressed as a percentage of the brain area examined) associated with β-amyloid deposits in the cortex Tg PS1/APPswe receiving regular drinking water (placebo) and the Anatabine treatment at a dosage of 10 and 20 mg/Kg/Day. ANOVA shows a statistically significant main effect of the Anatabine treatment on phosphorylated p65 NFκB immunoreactive cells associated with Aβ deposits (P

  • Anatabine reduces microgliosis in the brain of Tg PS1/APPswe mice.
    2015
    Co-Authors: Megha Verma, David Beaulieu-abdelahad, Ghania Ait-ghezala, Fiona Crawford, Michael Mullan, Daniel Paris
    Abstract:

    A) Representative 40X microscopic fields revealing Iba1 immunoreactive microglial cells in the hippocampus and the cortex of wild-type placebo and Tg PS1/APPswe receiving regular drinking water (placebo) and Tg PS1/APPswe mice receiving Anatabine at a dosage of 10 and 20 mg/Kg/Day dissolved in their drinking water. Data is presented as mean±SEM. B) The histogram represents the average amount of Iba1 burden (expressed as a percentage of the brain area examined) quantified in the hippocampus and the cortex of wild-type receiving regular drinking water (placebo) and Tg PS1/APPswe receiving either regular drinking water (placebo) or Anatabine at a dosage of 10 and 20 mg/Kg/Day dissolved in their drinking water. ANOVA reveals a significant main effect of the genotype on Iba1 burden in the hippocampus and cortex (P

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

  • Acute or Delayed Treatment with Anatabine Improves Spatial Memory and Reduces Pathological Sequelae at Late Time-Points after Repetitive Mild Traumatic Brain Injury
    Journal of neurotrauma, 2017
    Co-Authors: Scott Ferguson, Daniel Paris, Michael Mullan, Laila Abdullah, Benoit Mouzon, Destinee Aponte, William Stewart, Fiona Crawford
    Abstract:

    Abstract Traumatic brain injury (TBI) has chronic and long-term consequences for which there are currently no approved pharmacological treatments. We have previously characterized the chronic neurobehavioral and pathological sequelae of a mouse model of repetitive mild TBI (r-mTBI) through to 2 years post-TBI. Despite the mild nature of the initial insult, secondary injury processes are initiated that involve neuroinflammatory and neurodegenerative pathways persisting and progressing for weeks and months post-injury and providing a potential window of opportunity for therapeutic intervention. In this study we examined the efficacy of a novel anti-inflammatory compound, Anatabine, in modifying outcome after TBI. Our model of r-mTBI involves a series of five mild impacts (midline impact at 5 m/sec, 1 mm strike depth, 200 msec dwell time) with an interval of 48 h. Anatabine treatment was administered starting 30 min after injury and was delivered continuously through drinking water. At 6 months after TBI, an...

  • Chronic Anatabine Treatment Reduces Alzheimer’s Disease (AD)-Like Pathology and Improves Socio-Behavioral Deficits in a Transgenic Mouse Model of AD
    PloS one, 2015
    Co-Authors: Megha Verma, David Beaulieu-abdelahad, Ghania Ait-ghezala, Fiona Crawford, Michael Mullan, Daniel Paris
    Abstract:

    Anatabine is a minor tobacco alkaloid, which is also found in plants of the Solanaceae family and displays a chemical structure similarity with nicotine. We have shown previously that Anatabine displays some anti-inflammatory properties and reduces microgliosis and tau phosphorylation in a pure mouse model of tauopathy. We therefore investigated the effects of a chronic oral treatment with Anatabine in a transgenic mouse model (Tg PS1/APPswe) of Alzheimer’s disease (AD) which displays pathological Aβ deposits, neuroinflammation and behavioral deficits. In the elevated plus maze, Tg PS1/APPswe mice exhibited hyperactivity and disinhibition compared to wild-type mice. Six and a half months of chronic oral Anatabine treatment, suppressed hyperactivity and disinhibition in Tg PS1/APPswe mice compared to Tg PS1/APPswe receiving regular drinking water. Tg PS1/APPswe mice also elicited profound social interaction and social memory deficits, which were both alleviated by the Anatabine treatment. We found that Anatabine reduces the activation of STAT3 and NFκB in the vicinity of Aβ deposits in Tg PS1/APPswe mice resulting in a reduction of the expression of some of their target genes including Bace1, iNOS and Cox-2. In addition, a significant reduction in microgliosis and pathological deposition of Aβ was observed in the brain of Tg PS1/APPswe mice treated with Anatabine. This is the first study to investigate the impact of chronic Anatabine treatment on AD-like pathology and behavior in a transgenic mouse model of AD. Overall, our data show that Anatabine reduces β-amyloidosis, neuroinflammation and alleviates some behavioral deficits in Tg PS1/APPswe, supporting further exploration of Anatabine as a possible disease modifying agent for the treatment of AD.

  • chronic Anatabine treatment reduces alzheimer s disease ad like pathology and improves socio behavioral deficits in a transgenic mouse model of ad
    PLOS ONE, 2015
    Co-Authors: Fiona Crawford, Michael Mullan, Megha Verma, David Beaulieuabdelahad, Ghania Aitghezala, Daniel Paris
    Abstract:

    Anatabine is a minor tobacco alkaloid, which is also found in plants of the Solanaceae family and displays a chemical structure similarity with nicotine. We have shown previously that Anatabine displays some anti-inflammatory properties and reduces microgliosis and tau phosphorylation in a pure mouse model of tauopathy. We therefore investigated the effects of a chronic oral treatment with Anatabine in a transgenic mouse model (Tg PS1/APPswe) of Alzheimer’s disease (AD) which displays pathological Aβ deposits, neuroinflammation and behavioral deficits. In the elevated plus maze, Tg PS1/APPswe mice exhibited hyperactivity and disinhibition compared to wild-type mice. Six and a half months of chronic oral Anatabine treatment, suppressed hyperactivity and disinhibition in Tg PS1/APPswe mice compared to Tg PS1/APPswe receiving regular drinking water. Tg PS1/APPswe mice also elicited profound social interaction and social memory deficits, which were both alleviated by the Anatabine treatment. We found that Anatabine reduces the activation of STAT3 and NFκB in the vicinity of Aβ deposits in Tg PS1/APPswe mice resulting in a reduction of the expression of some of their target genes including Bace1, iNOS and Cox-2. In addition, a significant reduction in microgliosis and pathological deposition of Aβ was observed in the brain of Tg PS1/APPswe mice treated with Anatabine. This is the first study to investigate the impact of chronic Anatabine treatment on AD-like pathology and behavior in a transgenic mouse model of AD. Overall, our data show that Anatabine reduces β-amyloidosis, neuroinflammation and alleviates some behavioral deficits in Tg PS1/APPswe, supporting further exploration of Anatabine as a possible disease modifying agent for the treatment of AD.

  • Timeline of Anatabine treatment and behavior tests performed in Tg PS1/APPswe mice and their control wild-type littermate.
    2015
    Co-Authors: Megha Verma, David Beaulieu-abdelahad, Ghania Ait-ghezala, Fiona Crawford, Michael Mullan, Daniel Paris
    Abstract:

    Oral Anatabine treatment with 10mg/Kg/day or 20mg/Kg/Day was started in 10 months old Tg PS1/APPswe mice and control wild-type littermates and lasted for 6 and half months. During the course of treatment, a battery of behavior tasks was performed at the time points indicated above. Possible effects of the Anatabine treatment on anxiety in mice were evaluated using the elevated plus maze; 0.5 month and 2.5 months after the initiation of the Anatabine treatment (age of mice 10.5 and 12.5 months respectively). To evaluate the effects of Anatabine on social interaction and social memory, the 3-chamber test was used 6 months after the treatment initiation (age of mice 16 months). At the end of study mice were humanely euthanized at the age of 16.5 months for pathological evaluations.

  • Anatabine reduces hyperactivity and disinhibition in 12.5 month-old Tg PS1/APPswe mice.
    2015
    Co-Authors: Megha Verma, David Beaulieu-abdelahad, Ghania Ait-ghezala, Fiona Crawford, Michael Mullan, Daniel Paris
    Abstract:

    12.5 month-old Tg PS1/APPswe and their control littermates tested in EPM after treatment duration of 2.5 months with Anatabine. A) Representative path tracks in the closed and open arms of the elevated plus maze by 12.5 months old Tg PS1/APPswe and their control wild-type littermate receiving regular drinking water (placebo) and Anatabine at a dosage of 10 and 20 mg/Kg/Day in their drinking water are shown. B and C) The histogram represents the total distance travelled and mean velocity of Tg PS1/APPswe mice and their control wild-type littermates receiving regular drinking water (placebo) and Anatabine at a dosage of 10 or 20 mg/Kg/Day. ANOVA showed a significant main effect of the genotype for the distance travelled (P

Fiona Crawford - One of the best experts on this subject based on the ideXlab platform.

  • Acute or Delayed Treatment with Anatabine Improves Spatial Memory and Reduces Pathological Sequelae at Late Time-Points after Repetitive Mild Traumatic Brain Injury
    Journal of neurotrauma, 2017
    Co-Authors: Scott Ferguson, Daniel Paris, Michael Mullan, Laila Abdullah, Benoit Mouzon, Destinee Aponte, William Stewart, Fiona Crawford
    Abstract:

    Abstract Traumatic brain injury (TBI) has chronic and long-term consequences for which there are currently no approved pharmacological treatments. We have previously characterized the chronic neurobehavioral and pathological sequelae of a mouse model of repetitive mild TBI (r-mTBI) through to 2 years post-TBI. Despite the mild nature of the initial insult, secondary injury processes are initiated that involve neuroinflammatory and neurodegenerative pathways persisting and progressing for weeks and months post-injury and providing a potential window of opportunity for therapeutic intervention. In this study we examined the efficacy of a novel anti-inflammatory compound, Anatabine, in modifying outcome after TBI. Our model of r-mTBI involves a series of five mild impacts (midline impact at 5 m/sec, 1 mm strike depth, 200 msec dwell time) with an interval of 48 h. Anatabine treatment was administered starting 30 min after injury and was delivered continuously through drinking water. At 6 months after TBI, an...

  • Chronic Anatabine Treatment Reduces Alzheimer’s Disease (AD)-Like Pathology and Improves Socio-Behavioral Deficits in a Transgenic Mouse Model of AD
    PloS one, 2015
    Co-Authors: Megha Verma, David Beaulieu-abdelahad, Ghania Ait-ghezala, Fiona Crawford, Michael Mullan, Daniel Paris
    Abstract:

    Anatabine is a minor tobacco alkaloid, which is also found in plants of the Solanaceae family and displays a chemical structure similarity with nicotine. We have shown previously that Anatabine displays some anti-inflammatory properties and reduces microgliosis and tau phosphorylation in a pure mouse model of tauopathy. We therefore investigated the effects of a chronic oral treatment with Anatabine in a transgenic mouse model (Tg PS1/APPswe) of Alzheimer’s disease (AD) which displays pathological Aβ deposits, neuroinflammation and behavioral deficits. In the elevated plus maze, Tg PS1/APPswe mice exhibited hyperactivity and disinhibition compared to wild-type mice. Six and a half months of chronic oral Anatabine treatment, suppressed hyperactivity and disinhibition in Tg PS1/APPswe mice compared to Tg PS1/APPswe receiving regular drinking water. Tg PS1/APPswe mice also elicited profound social interaction and social memory deficits, which were both alleviated by the Anatabine treatment. We found that Anatabine reduces the activation of STAT3 and NFκB in the vicinity of Aβ deposits in Tg PS1/APPswe mice resulting in a reduction of the expression of some of their target genes including Bace1, iNOS and Cox-2. In addition, a significant reduction in microgliosis and pathological deposition of Aβ was observed in the brain of Tg PS1/APPswe mice treated with Anatabine. This is the first study to investigate the impact of chronic Anatabine treatment on AD-like pathology and behavior in a transgenic mouse model of AD. Overall, our data show that Anatabine reduces β-amyloidosis, neuroinflammation and alleviates some behavioral deficits in Tg PS1/APPswe, supporting further exploration of Anatabine as a possible disease modifying agent for the treatment of AD.

  • chronic Anatabine treatment reduces alzheimer s disease ad like pathology and improves socio behavioral deficits in a transgenic mouse model of ad
    PLOS ONE, 2015
    Co-Authors: Fiona Crawford, Michael Mullan, Megha Verma, David Beaulieuabdelahad, Ghania Aitghezala, Daniel Paris
    Abstract:

    Anatabine is a minor tobacco alkaloid, which is also found in plants of the Solanaceae family and displays a chemical structure similarity with nicotine. We have shown previously that Anatabine displays some anti-inflammatory properties and reduces microgliosis and tau phosphorylation in a pure mouse model of tauopathy. We therefore investigated the effects of a chronic oral treatment with Anatabine in a transgenic mouse model (Tg PS1/APPswe) of Alzheimer’s disease (AD) which displays pathological Aβ deposits, neuroinflammation and behavioral deficits. In the elevated plus maze, Tg PS1/APPswe mice exhibited hyperactivity and disinhibition compared to wild-type mice. Six and a half months of chronic oral Anatabine treatment, suppressed hyperactivity and disinhibition in Tg PS1/APPswe mice compared to Tg PS1/APPswe receiving regular drinking water. Tg PS1/APPswe mice also elicited profound social interaction and social memory deficits, which were both alleviated by the Anatabine treatment. We found that Anatabine reduces the activation of STAT3 and NFκB in the vicinity of Aβ deposits in Tg PS1/APPswe mice resulting in a reduction of the expression of some of their target genes including Bace1, iNOS and Cox-2. In addition, a significant reduction in microgliosis and pathological deposition of Aβ was observed in the brain of Tg PS1/APPswe mice treated with Anatabine. This is the first study to investigate the impact of chronic Anatabine treatment on AD-like pathology and behavior in a transgenic mouse model of AD. Overall, our data show that Anatabine reduces β-amyloidosis, neuroinflammation and alleviates some behavioral deficits in Tg PS1/APPswe, supporting further exploration of Anatabine as a possible disease modifying agent for the treatment of AD.

  • Anatabine reduces the amount of phosphorylated p65 NFκB immunopositive cells associated with β-amyloid deposits in the cortex of Tg PS1/APPswe mice.
    2015
    Co-Authors: Megha Verma, David Beaulieu-abdelahad, Ghania Ait-ghezala, Fiona Crawford, Michael Mullan, Daniel Paris
    Abstract:

    A) Representative 40X microscopic field revealing the presence of phosphorylated p65 NFκB immunopositive cells around Congo red stained β-amyloid deposits in the cortex of Tg PS1/APPswe mice receiving regular drinking water (placebo) or Anatabine at a dosage of 10 and 20 mg/Kg/Day in their drinking water. Data is presented as mean±SEM. B) The histogram represents the average amount of phospho p65 NFκB burden (expressed as a percentage of the brain area examined) associated with β-amyloid deposits in the cortex Tg PS1/APPswe receiving regular drinking water (placebo) and the Anatabine treatment at a dosage of 10 and 20 mg/Kg/Day. ANOVA shows a statistically significant main effect of the Anatabine treatment on phosphorylated p65 NFκB immunoreactive cells associated with Aβ deposits (P

  • Anatabine reduces microgliosis in the brain of Tg PS1/APPswe mice.
    2015
    Co-Authors: Megha Verma, David Beaulieu-abdelahad, Ghania Ait-ghezala, Fiona Crawford, Michael Mullan, Daniel Paris
    Abstract:

    A) Representative 40X microscopic fields revealing Iba1 immunoreactive microglial cells in the hippocampus and the cortex of wild-type placebo and Tg PS1/APPswe receiving regular drinking water (placebo) and Tg PS1/APPswe mice receiving Anatabine at a dosage of 10 and 20 mg/Kg/Day dissolved in their drinking water. Data is presented as mean±SEM. B) The histogram represents the average amount of Iba1 burden (expressed as a percentage of the brain area examined) quantified in the hippocampus and the cortex of wild-type receiving regular drinking water (placebo) and Tg PS1/APPswe receiving either regular drinking water (placebo) or Anatabine at a dosage of 10 and 20 mg/Kg/Day dissolved in their drinking water. ANOVA reveals a significant main effect of the genotype on Iba1 burden in the hippocampus and cortex (P

Megha Verma - One of the best experts on this subject based on the ideXlab platform.

  • Chronic Anatabine Treatment Reduces Alzheimer’s Disease (AD)-Like Pathology and Improves Socio-Behavioral Deficits in a Transgenic Mouse Model of AD
    PloS one, 2015
    Co-Authors: Megha Verma, David Beaulieu-abdelahad, Ghania Ait-ghezala, Fiona Crawford, Michael Mullan, Daniel Paris
    Abstract:

    Anatabine is a minor tobacco alkaloid, which is also found in plants of the Solanaceae family and displays a chemical structure similarity with nicotine. We have shown previously that Anatabine displays some anti-inflammatory properties and reduces microgliosis and tau phosphorylation in a pure mouse model of tauopathy. We therefore investigated the effects of a chronic oral treatment with Anatabine in a transgenic mouse model (Tg PS1/APPswe) of Alzheimer’s disease (AD) which displays pathological Aβ deposits, neuroinflammation and behavioral deficits. In the elevated plus maze, Tg PS1/APPswe mice exhibited hyperactivity and disinhibition compared to wild-type mice. Six and a half months of chronic oral Anatabine treatment, suppressed hyperactivity and disinhibition in Tg PS1/APPswe mice compared to Tg PS1/APPswe receiving regular drinking water. Tg PS1/APPswe mice also elicited profound social interaction and social memory deficits, which were both alleviated by the Anatabine treatment. We found that Anatabine reduces the activation of STAT3 and NFκB in the vicinity of Aβ deposits in Tg PS1/APPswe mice resulting in a reduction of the expression of some of their target genes including Bace1, iNOS and Cox-2. In addition, a significant reduction in microgliosis and pathological deposition of Aβ was observed in the brain of Tg PS1/APPswe mice treated with Anatabine. This is the first study to investigate the impact of chronic Anatabine treatment on AD-like pathology and behavior in a transgenic mouse model of AD. Overall, our data show that Anatabine reduces β-amyloidosis, neuroinflammation and alleviates some behavioral deficits in Tg PS1/APPswe, supporting further exploration of Anatabine as a possible disease modifying agent for the treatment of AD.

  • chronic Anatabine treatment reduces alzheimer s disease ad like pathology and improves socio behavioral deficits in a transgenic mouse model of ad
    PLOS ONE, 2015
    Co-Authors: Fiona Crawford, Michael Mullan, Megha Verma, David Beaulieuabdelahad, Ghania Aitghezala, Daniel Paris
    Abstract:

    Anatabine is a minor tobacco alkaloid, which is also found in plants of the Solanaceae family and displays a chemical structure similarity with nicotine. We have shown previously that Anatabine displays some anti-inflammatory properties and reduces microgliosis and tau phosphorylation in a pure mouse model of tauopathy. We therefore investigated the effects of a chronic oral treatment with Anatabine in a transgenic mouse model (Tg PS1/APPswe) of Alzheimer’s disease (AD) which displays pathological Aβ deposits, neuroinflammation and behavioral deficits. In the elevated plus maze, Tg PS1/APPswe mice exhibited hyperactivity and disinhibition compared to wild-type mice. Six and a half months of chronic oral Anatabine treatment, suppressed hyperactivity and disinhibition in Tg PS1/APPswe mice compared to Tg PS1/APPswe receiving regular drinking water. Tg PS1/APPswe mice also elicited profound social interaction and social memory deficits, which were both alleviated by the Anatabine treatment. We found that Anatabine reduces the activation of STAT3 and NFκB in the vicinity of Aβ deposits in Tg PS1/APPswe mice resulting in a reduction of the expression of some of their target genes including Bace1, iNOS and Cox-2. In addition, a significant reduction in microgliosis and pathological deposition of Aβ was observed in the brain of Tg PS1/APPswe mice treated with Anatabine. This is the first study to investigate the impact of chronic Anatabine treatment on AD-like pathology and behavior in a transgenic mouse model of AD. Overall, our data show that Anatabine reduces β-amyloidosis, neuroinflammation and alleviates some behavioral deficits in Tg PS1/APPswe, supporting further exploration of Anatabine as a possible disease modifying agent for the treatment of AD.

  • Timeline of Anatabine treatment and behavior tests performed in Tg PS1/APPswe mice and their control wild-type littermate.
    2015
    Co-Authors: Megha Verma, David Beaulieu-abdelahad, Ghania Ait-ghezala, Fiona Crawford, Michael Mullan, Daniel Paris
    Abstract:

    Oral Anatabine treatment with 10mg/Kg/day or 20mg/Kg/Day was started in 10 months old Tg PS1/APPswe mice and control wild-type littermates and lasted for 6 and half months. During the course of treatment, a battery of behavior tasks was performed at the time points indicated above. Possible effects of the Anatabine treatment on anxiety in mice were evaluated using the elevated plus maze; 0.5 month and 2.5 months after the initiation of the Anatabine treatment (age of mice 10.5 and 12.5 months respectively). To evaluate the effects of Anatabine on social interaction and social memory, the 3-chamber test was used 6 months after the treatment initiation (age of mice 16 months). At the end of study mice were humanely euthanized at the age of 16.5 months for pathological evaluations.

  • Anatabine reduces hyperactivity and disinhibition in 12.5 month-old Tg PS1/APPswe mice.
    2015
    Co-Authors: Megha Verma, David Beaulieu-abdelahad, Ghania Ait-ghezala, Fiona Crawford, Michael Mullan, Daniel Paris
    Abstract:

    12.5 month-old Tg PS1/APPswe and their control littermates tested in EPM after treatment duration of 2.5 months with Anatabine. A) Representative path tracks in the closed and open arms of the elevated plus maze by 12.5 months old Tg PS1/APPswe and their control wild-type littermate receiving regular drinking water (placebo) and Anatabine at a dosage of 10 and 20 mg/Kg/Day in their drinking water are shown. B and C) The histogram represents the total distance travelled and mean velocity of Tg PS1/APPswe mice and their control wild-type littermates receiving regular drinking water (placebo) and Anatabine at a dosage of 10 or 20 mg/Kg/Day. ANOVA showed a significant main effect of the genotype for the distance travelled (P

  • Anatabine reduces the amount of phosphorylated p65 NFκB immunopositive cells associated with β-amyloid deposits in the cortex of Tg PS1/APPswe mice.
    2015
    Co-Authors: Megha Verma, David Beaulieu-abdelahad, Ghania Ait-ghezala, Fiona Crawford, Michael Mullan, Daniel Paris
    Abstract:

    A) Representative 40X microscopic field revealing the presence of phosphorylated p65 NFκB immunopositive cells around Congo red stained β-amyloid deposits in the cortex of Tg PS1/APPswe mice receiving regular drinking water (placebo) or Anatabine at a dosage of 10 and 20 mg/Kg/Day in their drinking water. Data is presented as mean±SEM. B) The histogram represents the average amount of phospho p65 NFκB burden (expressed as a percentage of the brain area examined) associated with β-amyloid deposits in the cortex Tg PS1/APPswe receiving regular drinking water (placebo) and the Anatabine treatment at a dosage of 10 and 20 mg/Kg/Day. ANOVA shows a statistically significant main effect of the Anatabine treatment on phosphorylated p65 NFκB immunoreactive cells associated with Aβ deposits (P

Ghania Ait-ghezala - One of the best experts on this subject based on the ideXlab platform.

  • Chronic Anatabine Treatment Reduces Alzheimer’s Disease (AD)-Like Pathology and Improves Socio-Behavioral Deficits in a Transgenic Mouse Model of AD
    PloS one, 2015
    Co-Authors: Megha Verma, David Beaulieu-abdelahad, Ghania Ait-ghezala, Fiona Crawford, Michael Mullan, Daniel Paris
    Abstract:

    Anatabine is a minor tobacco alkaloid, which is also found in plants of the Solanaceae family and displays a chemical structure similarity with nicotine. We have shown previously that Anatabine displays some anti-inflammatory properties and reduces microgliosis and tau phosphorylation in a pure mouse model of tauopathy. We therefore investigated the effects of a chronic oral treatment with Anatabine in a transgenic mouse model (Tg PS1/APPswe) of Alzheimer’s disease (AD) which displays pathological Aβ deposits, neuroinflammation and behavioral deficits. In the elevated plus maze, Tg PS1/APPswe mice exhibited hyperactivity and disinhibition compared to wild-type mice. Six and a half months of chronic oral Anatabine treatment, suppressed hyperactivity and disinhibition in Tg PS1/APPswe mice compared to Tg PS1/APPswe receiving regular drinking water. Tg PS1/APPswe mice also elicited profound social interaction and social memory deficits, which were both alleviated by the Anatabine treatment. We found that Anatabine reduces the activation of STAT3 and NFκB in the vicinity of Aβ deposits in Tg PS1/APPswe mice resulting in a reduction of the expression of some of their target genes including Bace1, iNOS and Cox-2. In addition, a significant reduction in microgliosis and pathological deposition of Aβ was observed in the brain of Tg PS1/APPswe mice treated with Anatabine. This is the first study to investigate the impact of chronic Anatabine treatment on AD-like pathology and behavior in a transgenic mouse model of AD. Overall, our data show that Anatabine reduces β-amyloidosis, neuroinflammation and alleviates some behavioral deficits in Tg PS1/APPswe, supporting further exploration of Anatabine as a possible disease modifying agent for the treatment of AD.

  • Anatabine reduces the amount of phosphorylated p65 NFκB immunopositive cells associated with β-amyloid deposits in the cortex of Tg PS1/APPswe mice.
    2015
    Co-Authors: Megha Verma, David Beaulieu-abdelahad, Ghania Ait-ghezala, Fiona Crawford, Michael Mullan, Daniel Paris
    Abstract:

    A) Representative 40X microscopic field revealing the presence of phosphorylated p65 NFκB immunopositive cells around Congo red stained β-amyloid deposits in the cortex of Tg PS1/APPswe mice receiving regular drinking water (placebo) or Anatabine at a dosage of 10 and 20 mg/Kg/Day in their drinking water. Data is presented as mean±SEM. B) The histogram represents the average amount of phospho p65 NFκB burden (expressed as a percentage of the brain area examined) associated with β-amyloid deposits in the cortex Tg PS1/APPswe receiving regular drinking water (placebo) and the Anatabine treatment at a dosage of 10 and 20 mg/Kg/Day. ANOVA shows a statistically significant main effect of the Anatabine treatment on phosphorylated p65 NFκB immunoreactive cells associated with Aβ deposits (P

  • Anatabine reduces microgliosis in the brain of Tg PS1/APPswe mice.
    2015
    Co-Authors: Megha Verma, David Beaulieu-abdelahad, Ghania Ait-ghezala, Fiona Crawford, Michael Mullan, Daniel Paris
    Abstract:

    A) Representative 40X microscopic fields revealing Iba1 immunoreactive microglial cells in the hippocampus and the cortex of wild-type placebo and Tg PS1/APPswe receiving regular drinking water (placebo) and Tg PS1/APPswe mice receiving Anatabine at a dosage of 10 and 20 mg/Kg/Day dissolved in their drinking water. Data is presented as mean±SEM. B) The histogram represents the average amount of Iba1 burden (expressed as a percentage of the brain area examined) quantified in the hippocampus and the cortex of wild-type receiving regular drinking water (placebo) and Tg PS1/APPswe receiving either regular drinking water (placebo) or Anatabine at a dosage of 10 and 20 mg/Kg/Day dissolved in their drinking water. ANOVA reveals a significant main effect of the genotype on Iba1 burden in the hippocampus and cortex (P

  • Anatabine improves social interaction and social memory in Tg PS1/APPswe mice.
    2015
    Co-Authors: Megha Verma, David Beaulieu-abdelahad, Ghania Ait-ghezala, Fiona Crawford, Michael Mullan, Daniel Paris
    Abstract:

    A) The histogram represents the mean time spent ± SEM by Tg PS1/APPswe and their control wild-type littermates mouse receiving regular drinking water in the chamber containing the Stranger1 and the empty cage for the social interaction phase of 3-chamber test. B) The histogram represents the time spent ± SEM by Tg PS1/APPswe receiving regular drinking water or Anatabine at a dosage of 10 and 20 mg/Kg/Day in the chamber containing the Stranger 1 and the empty cage for the social interaction phase of 3-chamber test. Tg PS1/APPswe mice receiving regular drinking water spent the same amount of time in the chamber containing the stranger 1 and the empty cage (P>0.05). Tg PS1/APPswe mice receiving Anatabine at a dosage of 20mg/Kg/Day spent significantly more time exploring the chamber containing the Stranger1 than the chamber containing the empty cage (P0.05). Tg PS1/APPswe mice receiving Anatabine at a dosage of 10 and 20 mg/Kg/Day spent significantly more time exploring the chamber containing the unfamiliar Stranger 2 than the chamber containing the previously encountered mouse (Stranger 1) (P

  • Anatabine reduces β-amyloidosis in the hippocampus and the cortex of Tg PS1/APPswe mice.
    2015
    Co-Authors: Megha Verma, David Beaulieu-abdelahad, Ghania Ait-ghezala, Fiona Crawford, Michael Mullan, Daniel Paris
    Abstract:

    A) Representative 20X microscopic fields showing β-amyloid deposits (4G8 immunostaining) in the cortex and hippocampus of Tg PS1/APPswe receiving regular drinking water (placebo) and Anatabine at a dosage of 10 and 20 mg/Kg/Day dissolved in their drinking water are shown. Data is presented as mean±SEM. B) The histogram represents the average amount of 4G8 burden quantified in the hippocampus and cortex of Tg PS1/APPswe mice. ANOVA shows a statistically significant main effect of the Anatabine treatment (P