title: The radical scavenger IAC (bis(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl) decantionate) decreases mortality, enhances cognitive functions in water maze and reduces amyloid plaque burden in hAβPP transgenic mice.
abstract: The purpose of this study was to evaluate the efficacy of the radical scavenger IAC (bis(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl) decantionate) in alleviating behavioral deficits and reducing amyloid-β (Aβ) accumulation in an Alzheimer's disease (AD) transgenic Tg2576 mouse model. Daily treatment with IAC (3-30 mg/kg, i.p.) was started at the age of 6 months and continued until the mice were 13 months old. At the age of 9 months and again at 12 months, the mice were tested in open field and water maze tests. At the age of 13 months, the mice were sacrificed and the brains processed for immunohistochemistry. Mortality was significantly reduced in all IAC-treated groups. In addition, IAC treatment improved the water maze hidden platform training performance but had no effect on motor activity in the open field or water maze swim speed in transgenic mice. Lastly, IAC treatment (10 mg/kg) significantly reduced the cortical Aβ plaque burden. In vitro, IAC is able to increase the number of neurites and neurite branches in cultured cortical primary neurons. In conclusion, IAC slowed down the development of the AD-like phenotype in Tg2576 mice and accelerated neurite growth in cultured neurons.
authors.affiliation: Cerebricon Limited, Kuopio, Finland.
authors.forename: Jukka
authors.initials: J
authors.lastname: Puoliväli
authors.forename: Antti
authors.initials: A
authors.lastname: Nurmi
authors.forename: Taina-Kaisa
authors.initials: TK
authors.lastname: Miettinen
authors.forename: Antonio
authors.initials: A
authors.lastname: Soleti
authors.forename: Francesca
authors.initials: F
authors.lastname: Riccardino
authors.forename: Giedrius
authors.initials: G
authors.lastname: Kalesnykas
authors.forename: Taneli
authors.initials: T
authors.lastname: Heikkinen
authors.forename: Nina
authors.initials: N
authors.lastname: Vartiainen
authors.forename: Raimo
authors.initials: R
authors.lastname: Pussinen
authors.forename: Leena
authors.initials: L
authors.lastname: Tähtivaara
authors.forename: Kimmo
authors.initials: K
authors.lastname: Lehtimäki
authors.forename: Juha
authors.initials: J
authors.lastname: Yrjänheikki
authors.forename: Donatella
authors.initials: D
authors.lastname: Canistro
authors.forename: Andrea
authors.initials: A
authors.lastname: Sapone
authors.forename: Enzo
authors.initials: E
authors.lastname: Spisni
authors.forename: Moreno
authors.initials: M
authors.lastname: Paolini
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003071:Cognition / Q000187:drug effects / Q000502:physiology*; D006224:Cricetinae; D004195:Disease Models, Animal; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use*; D058225:Plaque, Amyloid / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D016564:Amyloid beta-Protein Precursor; D016166:Free Radical Scavengers; D010880:Piperidines; C526136:bis(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)decandioate