Adipose-derived stem cell-conditioned medium ameliorates antidepression-related behaviors in the mouse model of Alzheimer's disease.

The present study investigated the effect of adipose-derived stem cell-conditioned medium (ASC-CM) on behavioral disorders in 5xFAD transgenic mice, a model of Alzheimer's disease (AD). The immobility time in the tail suspension and forced swim tests for 5xFAD mice was shorter than that for wild-type mice. Intravenous injection with ASC-CM restored the shortened immobility time for 5xFAD mice to the normal levels or to an extent, being still persistent 4 weeks after injection. ASC-CM significantly suppressed phosphorylation of Akt at Ser473 and glycogen synthase kinase 3β (GSK-3β) at Ser9 in the hypothalamus of 5xFAD mice, without affecting Tau phosphorylation, as compared with that for control 5xFAD mice without ASC-CM injection. ASC-CM did not affect cell surface localization of the N-methyl-d-aspartate (NMDA) receptor subunits NR1, -2A, and -2B both in the hippocampus and hypothalamus of 5xFAD mice. The results of the present study show that ASC-CM ameliorates antidepression-related behaviors in 5xFAD mice, perhaps by inhibiting Akt and activating GSK-3β.