Early detection of memory deficits and memory improvement with vaccinia virus complement control protein in an Alzheimer's disease model.
Vaccinia virus complement control protein (VCP) inhibits both the classical and alternate complement pathways. In diseases such as traumatic brain injury (TBI) and Alzheimer's disease (AD), pathological inflammation is caused by amongst several factors, prolonged or inappropriate activation of the complement system and is a significant cause of neurodegeneration. This study investigates for the first time the use of a cheeseboard maze to evaluate cognitive deficits and the effect of VCP on memory processes in 2- and 3-month-old mice that express mutant amyloid precursor protein (APPswe) and mutant presenilin 1 (Ps1dE9) that correspond to a form of early onset AD. A four-phase training schedule was carried out on the cheeseboard maze before intracranial injections of 5 microl of VCP (1.7 microg/microl) or 5 microl saline. Two weeks later the effect of VCP on memory was evaluated. A statistically significant decrease in goal latency in VCP-treated mice than saline-treated transgenic mice in both the first probe and reverse tasks was observed. Similarly, after a second intracranial VCP or saline injection performed 2 months later, the 6.5- and 7.5-month aged VCP-injected mice performed significantly better in goal latency in both second probe and reverse tasks than saline-treated mice. These data also demonstrated that the use of a dry maze is a sensitive technique for distinguishing cognitive measures between non-transgenic and APPswe/PS1De9 transgenic mice at a much earlier stage.
Pillay
Nirvana S
NS
Division of Medical Virology, South Africa.
Kellaway
Laurie A
LA
Kotwal
Girish J
GJ
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D042241:Early Diagnosis; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D008569:Memory Disorders / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D051379:Mice; D008822:Mice, Transgenic; D008845:Microinjections / Q000379:methods; D009154:Mutation; D053764:Presenilin-1 / Q000235:genetics; D013037:Spatial Behavior / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D016896:Treatment Outcome; D014764:Viral Proteins / Q000008:administration & dosage / Q000494:pharmacology*
D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1; D014764:Viral Proteins; C066459:complement-control protein, Vaccinia virus