Testing the calcium hypothesis of aging in the rat hippocampus in vivo using manganese-enhanced MRI.
In this study, we noninvasively tested the hypothesis that Mn(2+)-enhanced magnetic resonance imaging (MEMRI) is sensitive to age-related changes in Ca(2+) influx occurring in the hippocampal region CA1. Uptake of Mn(2+), an MRI contrast agent and Ca(2+) surrogate with low cellular efflux rates (days to weeks), was measured in longitudinal MEMRI studies involving 2 separate groups of male Long-Evans rats: one group was studied at 2.5 and 7 months of age, whereas the other was studied at 7 and 19 months of age. Separate or combined analysis revealed that the extent of Mn(2+) accumulation in CA1 significantly increased with age (p < 0.05). These results provide first-time in vivo confirmation of the calcium hypothesis of aging and justify future longitudinal studies combining MEMRI with behavioral testing to investigate mechanisms of age-related cognitive decline.
Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI, USA.
David
D
Bissig
Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI, USA; Department of Ophthalmology, Wayne State University School of Medicine, Detroit, MI, USA. Electronic address: baberko@med.wayne.edu.
Bruce A
BA
Berkowitz
D000375:Aging / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000378:metabolism / Q000473:pathology*; D002118:Calcium / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism; D003072:Cognition Disorders / Q000175:diagnosis / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D017895:Manganese Compounds / Q000378:metabolism; D059906:Neuroimaging / Q000379:methods*; D051381:Rats; D020318:Rats, Long-Evans
D002712:Chlorides; D017895:Manganese Compounds; C025340:manganese chloride; D002118:Calcium
Aging; CA1; Hippocampus; MRI; Manganese; Rat