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


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.


RESULTS
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.


CONCLUSIONS
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.
NYS Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA.
Wenzhong
W
Yang
NYS Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA.
Abha
A
Chauhan
NYS Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA.
Sangita
S
Mehta
NYS Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA.
Pankaj
P
Mehta
NYS Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA.
Feng
F
Gu
NYS Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA. Electronic address: ved.chauhan@opwdd.ny.gov.
Ved
V
Chauhan
D000544:Alzheimer Disease / Q000097:blood*; D016229:Amyloid beta-Peptides / Q000097:blood* / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D001835:Body Weight; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D018260:Gelsolin / Q000097:blood* / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006877:Hydroxamic Acids / Q000494:pharmacology*; D007263:Infusions, Parenteral; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000097:blood* / Q000235:genetics* / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D018260:Gelsolin; D006877:Hydroxamic Acids; D010446:Peptide Fragments; D011500:Protein Synthesis Inhibitors; C078592:amyloid beta-protein (1-40); C012589:trichostatin A
Alzheimer's disease; Amyloid beta-protein; Gelsolin; Histone deacetylase; Transgenic mice; Trichostatin A