The effects of enhanced zinc on spatial memory and plaque formation in transgenic mice.
There is considerable evidence suggesting that metals play a central role in the pathogenesis of Alzheimer's disease. Reports suggest that elevated dietary metals may both precipitate and potentiate an Alzheimer's disease phenotype. Despite this, there remain few studies that have examined the behavioral consequences of elevated dietary metals in wild type and Alzheimer's disease animals. To further investigate this in the current study, two separate transgenic models of AD (Tg2576 and TgCRND8), together with wild type littermates were administered 10 ppm (0.153 mM) Zn. Tg2576 animals were maintained on a zinc-enriched diet both pre- and postnatally until 11 months of age, while TgCRND8 animals were treated for five months following weaning. Behavioral testing, consisting of "Atlantis" and "moving" platform versions of the Morris water maze, were conducted at the end of the study, and tissues were collected for immunohistochemical analysis of amyloid-beta burden. Our data demonstrate that the provision of a zinc-enriched diet potentiated Alzheimer-like spatial memory impairments in the transgenic animals and was associated with reduced hippocampal amyloid-beta plaque deposits. Zinc-related behavioral deficits were also demonstrated in wild type mice, which were sometimes as great as those present in the transgenic animals. However, zinc-related cognitive impairments in transgenic mice were greater than the summation of zinc effects in the wild type mice and the transgene effects.
Linkous
David H
DH
Department of Psychology, George Mason University, Fairfax, VA 22030, USA.
Adlard
Paul A
PA
Wanschura
Patricia B
PB
Conko
Kathryn M
KM
Flinn
Jane M
JM
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D004032:Diet; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008569:Memory Disorders / Q000175:diagnosis* / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D013028:Space Perception / Q000187:drug effects*; D015032:Zinc / Q000008:administration & dosage / Q000009:adverse effects* / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D015032:Zinc