Involvement of astroglial ceramide in palmitic acid-induced Alzheimer-like changes in primary neurons

Sachin Patil, Joseph Melrose, Christina Chan

    Research output: Research - peer-reviewArticle

    • 61 Citations

    Abstract

    A high-fat diet has been shown to significantly increase the risk of the development of Alzheimer's disease (AD), a neurodegenerative disease histochemically characterized by the accumulation of amyloid beta (Aβ) protein in senile plaques and hyperphosphorylated tau in neurofibrillary tangles. Previously, we have shown that saturated free fatty acids (FFAs), palmitic and stearic acids, caused increased amyloidogenesis and tau hyperphosphorylaion in primary rat cortical neurons. These FFA-induced effects observed in neurons were found to be mediated by astroglial FFA metabolism. Therefore, in the present study we investigated the basic mechanism relating astroglial FFA metabolism and AD-like changes observed in neurons. We found that palmitic acid significantly increased de-novo synthesis of ceramide in astroglia, which in turn was involved in inducing both increased production of the Aβ protein and hyperphosphorylation of the tau protein. Increased amyloidogenesis and hyperphoshorylation of tau lead to formation of the two most important pathophysiological characteristics associated with AD, Aβ or senile plaques and neurofibrillary tangles, respectively. In addition to these pathophysiological changes, AD is also characterized by certain metabolic changes; abnormal cerebral glucose metabolism is one of the distinct characteristics of AD. In this context, we found that palmitic acid significantly decreased the levels of astroglial glucose transporter (GLUT1) and down-regulated glucose uptake and lactate release by astroglia. Our present data establish an underlying mechanism by which saturated fatty acids induce AD-associated pathophysiological as well as metabolic changes, placing 'astroglial fatty acid metabolism' at the center of the pathogenic cascade in AD.

    LanguageEnglish (US)
    Pages2131-2141
    Number of pages11
    JournalEuropean Journal of Neuroscience
    Volume26
    Issue number8
    DOIs
    StatePublished - Oct 2007

    Profile

    Palmitic Acid
    Ceramides
    Alzheimer Disease
    Neurons
    Nonesterified Fatty Acids
    Fatty Acids
    Neurofibrillary Tangles
    Amyloid Plaques
    Astrocytes
    Glucose
    Stearic Acids
    tau Proteins
    Facilitative Glucose Transport Proteins
    Amyloid beta-Peptides
    High Fat Diet
    Neurodegenerative Diseases
    Lactic Acid
    Proteins

    Keywords

    • Alzheimer's disease
    • Astroglia
    • Ceramide
    • Fat
    • Rat

    ASJC Scopus subject areas

    • Neuroscience(all)

    Cite this

    Involvement of astroglial ceramide in palmitic acid-induced Alzheimer-like changes in primary neurons. / Patil, Sachin; Melrose, Joseph; Chan, Christina.

    In: European Journal of Neuroscience, Vol. 26, No. 8, 10.2007, p. 2131-2141.

    Research output: Research - peer-reviewArticle

    @article{cb28159849274dcdacd381a02c06f9cf,
    title = "Involvement of astroglial ceramide in palmitic acid-induced Alzheimer-like changes in primary neurons",
    abstract = "A high-fat diet has been shown to significantly increase the risk of the development of Alzheimer's disease (AD), a neurodegenerative disease histochemically characterized by the accumulation of amyloid beta (Aβ) protein in senile plaques and hyperphosphorylated tau in neurofibrillary tangles. Previously, we have shown that saturated free fatty acids (FFAs), palmitic and stearic acids, caused increased amyloidogenesis and tau hyperphosphorylaion in primary rat cortical neurons. These FFA-induced effects observed in neurons were found to be mediated by astroglial FFA metabolism. Therefore, in the present study we investigated the basic mechanism relating astroglial FFA metabolism and AD-like changes observed in neurons. We found that palmitic acid significantly increased de-novo synthesis of ceramide in astroglia, which in turn was involved in inducing both increased production of the Aβ protein and hyperphosphorylation of the tau protein. Increased amyloidogenesis and hyperphoshorylation of tau lead to formation of the two most important pathophysiological characteristics associated with AD, Aβ or senile plaques and neurofibrillary tangles, respectively. In addition to these pathophysiological changes, AD is also characterized by certain metabolic changes; abnormal cerebral glucose metabolism is one of the distinct characteristics of AD. In this context, we found that palmitic acid significantly decreased the levels of astroglial glucose transporter (GLUT1) and down-regulated glucose uptake and lactate release by astroglia. Our present data establish an underlying mechanism by which saturated fatty acids induce AD-associated pathophysiological as well as metabolic changes, placing 'astroglial fatty acid metabolism' at the center of the pathogenic cascade in AD.",
    keywords = "Alzheimer's disease, Astroglia, Ceramide, Fat, Rat",
    author = "Sachin Patil and Joseph Melrose and Christina Chan",
    year = "2007",
    month = "10",
    doi = "10.1111/j.1460-9568.2007.05797.x",
    volume = "26",
    pages = "2131--2141",
    journal = "European Journal of Neuroscience",
    issn = "0953-816X",
    publisher = "Wiley-Blackwell",
    number = "8",

    }

    TY - JOUR

    T1 - Involvement of astroglial ceramide in palmitic acid-induced Alzheimer-like changes in primary neurons

    AU - Patil,Sachin

    AU - Melrose,Joseph

    AU - Chan,Christina

    PY - 2007/10

    Y1 - 2007/10

    N2 - A high-fat diet has been shown to significantly increase the risk of the development of Alzheimer's disease (AD), a neurodegenerative disease histochemically characterized by the accumulation of amyloid beta (Aβ) protein in senile plaques and hyperphosphorylated tau in neurofibrillary tangles. Previously, we have shown that saturated free fatty acids (FFAs), palmitic and stearic acids, caused increased amyloidogenesis and tau hyperphosphorylaion in primary rat cortical neurons. These FFA-induced effects observed in neurons were found to be mediated by astroglial FFA metabolism. Therefore, in the present study we investigated the basic mechanism relating astroglial FFA metabolism and AD-like changes observed in neurons. We found that palmitic acid significantly increased de-novo synthesis of ceramide in astroglia, which in turn was involved in inducing both increased production of the Aβ protein and hyperphosphorylation of the tau protein. Increased amyloidogenesis and hyperphoshorylation of tau lead to formation of the two most important pathophysiological characteristics associated with AD, Aβ or senile plaques and neurofibrillary tangles, respectively. In addition to these pathophysiological changes, AD is also characterized by certain metabolic changes; abnormal cerebral glucose metabolism is one of the distinct characteristics of AD. In this context, we found that palmitic acid significantly decreased the levels of astroglial glucose transporter (GLUT1) and down-regulated glucose uptake and lactate release by astroglia. Our present data establish an underlying mechanism by which saturated fatty acids induce AD-associated pathophysiological as well as metabolic changes, placing 'astroglial fatty acid metabolism' at the center of the pathogenic cascade in AD.

    AB - A high-fat diet has been shown to significantly increase the risk of the development of Alzheimer's disease (AD), a neurodegenerative disease histochemically characterized by the accumulation of amyloid beta (Aβ) protein in senile plaques and hyperphosphorylated tau in neurofibrillary tangles. Previously, we have shown that saturated free fatty acids (FFAs), palmitic and stearic acids, caused increased amyloidogenesis and tau hyperphosphorylaion in primary rat cortical neurons. These FFA-induced effects observed in neurons were found to be mediated by astroglial FFA metabolism. Therefore, in the present study we investigated the basic mechanism relating astroglial FFA metabolism and AD-like changes observed in neurons. We found that palmitic acid significantly increased de-novo synthesis of ceramide in astroglia, which in turn was involved in inducing both increased production of the Aβ protein and hyperphosphorylation of the tau protein. Increased amyloidogenesis and hyperphoshorylation of tau lead to formation of the two most important pathophysiological characteristics associated with AD, Aβ or senile plaques and neurofibrillary tangles, respectively. In addition to these pathophysiological changes, AD is also characterized by certain metabolic changes; abnormal cerebral glucose metabolism is one of the distinct characteristics of AD. In this context, we found that palmitic acid significantly decreased the levels of astroglial glucose transporter (GLUT1) and down-regulated glucose uptake and lactate release by astroglia. Our present data establish an underlying mechanism by which saturated fatty acids induce AD-associated pathophysiological as well as metabolic changes, placing 'astroglial fatty acid metabolism' at the center of the pathogenic cascade in AD.

    KW - Alzheimer's disease

    KW - Astroglia

    KW - Ceramide

    KW - Fat

    KW - Rat

    UR - http://www.scopus.com/inward/record.url?scp=35448979511&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=35448979511&partnerID=8YFLogxK

    U2 - 10.1111/j.1460-9568.2007.05797.x

    DO - 10.1111/j.1460-9568.2007.05797.x

    M3 - Article

    VL - 26

    SP - 2131

    EP - 2141

    JO - European Journal of Neuroscience

    T2 - European Journal of Neuroscience

    JF - European Journal of Neuroscience

    SN - 0953-816X

    IS - 8

    ER -