Trichostatin A increases the levels of plasma gelsolin and amyloid beta-protein in a transgenic mouse model of Alzheimer's disease

Abstract

Aims: Gelsolin (GSN), a multifunctional protein, binds to amyloid beta-protein (Aβ), inhibits its fibrillization, solubilizes preformed Aβ fibrils, and helps in its clearance from the brain. Trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, induces the protein expression of gelsolin. In the present study, we investigated how TSA-treatment of APPswe/PS1δE9 transgenic (Tg) mice of Alzheimer's disease (AD) will affect the plasma levels of gelsolin and Aβ.

Main methods: TSA (5mg/kg body weight on alternate days for two months) was intraperitoneally injected to AD Tg mice. Gelsolin was measured by Western blotting and Aβ was measured by enzyme-linked immunosorbent assay.

Key findings: TSA-treatment significantly increased the levels of plasma gelsolin by 1.79-fold as compared with vehicle-treated control mice (p<0.01). The levels of Aβ 1-40 and Aβ 1-42 in the plasma were also higher in TSA-treated mice in comparison with vehicle-treated mice. The treatment of transgenic AD mice with TSA did not affect the body weight in both male and female groups as compared to vehicle-treated animals. A positive correlation was observed between the plasma levels of gelsolin and Aβ 1-40 (r=0.594, p=0.042) or Aβ 1-42 (r=0.616, p=0.033) in AD Tg mice.

Significance: These results suggest that TSA increases the levels of plasma gelsolin and Aβ in AD Tg mice, which may have implications in gelsolin-mediated clearance of Aβ.

Keywords: Alzheimer's disease; Amyloid beta-protein; Gelsolin; Histone deacetylase; Transgenic mice; Trichostatin A.