Rosiglitazone increases dendritic spine density and rescues spine loss caused by apolipoprotein E4 in primary cortical neurons.

Published

Journal Article

Convergent evidence has revealed an association between insulin resistance and Alzheimer's disease (AD), and the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist, rosiglitazone, an insulin sensitizer and mitochondrial activator, improves cognition in patients with early or mild-to-moderate AD. Apolipoprotein (apo) E4, a major genetic risk factor for AD, exerts neuropathological effects through multiple pathways, including impairment of dendritic spine structure and mitochondrial function. Here we show that rosiglitazone significantly increased dendritic spine density in a dose-dependent manner in cultured primary cortical rat neurons. This effect was abolished by the PPAR-gamma-specific antagonist, GW9662, suggesting that rosiglitazone exerts this effect by activating the PPAR-gamma pathway. Furthermore, the C-terminal-truncated fragment of apoE4 significantly decreased dendritic spine density. Rosiglitazone rescued this detrimental effect. Thus, rosiglitazone might improve cognition in AD patients by increasing dendritic spine density.

Full Text

Cited Authors

  • Brodbeck, J; Balestra, ME; Saunders, AM; Roses, AD; Mahley, RW; Huang, Y

Published Date

  • January 22, 2008

Published In

Volume / Issue

  • 105 / 4

Start / End Page

  • 1343 - 1346

PubMed ID

  • 18212130

Pubmed Central ID

  • 18212130

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.0709906104

Language

  • eng