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Neurotoxic Effects of Repetitive Inhibition of Oxidative Phosphorylation in Young Adults Surfacing With Deficits of Spatial Learning in Old Age

Department of Psychiatry, Charité Universitätsmedizin, Berlin, Germany.

Address correspondence to Matthias W. Riepe, MD, Department of Psychiatry, Campus Benjamin Franklin, Charité Medical University, Eschenallee 3, 14050 Berlin, Germany. E-mail: matthias.riepe{at}charite.de

Little is known about whether events in youth impact performance in old age. We examined spatial navigation in young (4.5 months) and middle-aged (9 months) CD-1 mice in a complex maze after treatment with 3-nitropropionate (3-np; 20 mg/kg body weight; 9 injections intraperitoneally [i.p.] every other day). Young mice treated with 3-np were examined in a mirror version of this maze in old age (22 months) and with a nonreference memory task of an eight-arm radial maze. The performance of young mice was affected to a small degree by treatment with 3-np. However, the performance of middle-aged mice severely declined on 3-np treatment. Animals treated at a young age with 3-np showed learning deficits in old age for both the complex maze and the radial maze. We conclude that exposure to repetitive inhibition of oxidative phosphorylation in youth leads to impairment of spatial learning surfacing in old age.