Intracranial administration of vaccinia virus complement control protein in Mo/Hu APPswe PS1dE9 transgenic mice at an early age shows enhanced performance at a later age using a cheese board maze test.
One of the key pro-inflammatory mediators activated by amyloid protein in neurodegenerative disorders of the brain, such as Alzheimer's disease is the complement system. Vaccinia virus complement control protein secreted by vaccinia virus, commonly known as VCP, was found to inhibit amyloid protein mediated up-regulation of complement system in vitro. In the current research investigation, VCP was administered twice (First dose at 3 weeks and the second dose at 6-7 months) intracranially into the parietal cortical area of Mo/Hu APPswe transgenic mice. At the age of 2 years or more, the same mice were subjected to cued-learning, spatial learning, probe and reverse probe trial paradigms of cheese board maze tasks for cognitive assessment. A significant difference was observed between VCP treated mice and the transgenic controls on days two and three of the cued trials and probe trials. The VCP treated group showed a similar trend as revealed during the spatial learning trial and reverse probe trial. A differential pattern of thioflavine S staining was observed in the VCP treated group. These results suggest that administration of VCP at an early age in transgenic mice may be effective in regulating the progression to the familial form of Alzheimer's disease at a later age.
Kulkarni
Amod P
AP
Division of Medical Virology, Department of Clinical Laboratory Sciences, Faculty of Health Sciences, Institute of Infectious Diseases and Molecular Medicine (IIDMM), University of Cape Town, Anzio Road, Observatory-07925, Cape Town, South Africa.
Pillay
Nirvana S
NS
Kellaway
Lauriston A
LA
Kotwal
Girish J
GJ
D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000544:Alzheimer Disease / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000686:Amyloidosis / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D000818:Animals; D001245:Association Learning / Q000187:drug effects / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D052160:Benzothiazoles; D003165:Complement System Proteins / Q000276:immunology; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D005838:Genotype; D007267:Injections; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D012193:Reversal Learning / Q000187:drug effects / Q000502:physiology; D013028:Space Perception / Q000187:drug effects / Q000502:physiology; D013844:Thiazoles / Q000378:metabolism; D014764:Viral Proteins / Q000494:pharmacology*
D016564:Amyloid beta-Protein Precursor; D052160:Benzothiazoles; D013844:Thiazoles; D014764:Viral Proteins; C066459:complement-control protein, Vaccinia virus; C009462:thioflavin T; D003165:Complement System Proteins