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

Sachin Patil, Joseph Melrose, Christina Chan

Research output: Contribution to journalArticle

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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
Neurofibrillary Tangles
Fatty Acids
Amyloid Plaques
Astrocytes
Stearic Acids
Glucose
tau Proteins
Facilitative Glucose Transport Proteins
Amyloid beta-Peptides
High Fat Diet
Neurodegenerative Diseases
Lactic Acid

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: Contribution to journalArticle

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