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

Abstract:

: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.

authors

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

doi

10.1073/pnas.0709906104

subject

Has Abstract

pub_date

2008-01-29 00:00:00

pages

1343-6

issue

4

eissn

0027-8424

issn

1091-6490

pii

0709906104

journal_volume

105

pub_type

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