Membrane-Free Stem Cells and Pyridoxal 5′-Phosphate Synergistically Enhance Cognitive Function in Alzheimer’s Disease Mouse Model

Abstract

Accumulation of amyloid beta (Aβ) is a major pathological hallmark of Alzheimer’s disease (AD). In this study, we evaluated the protective effect of membrane-free stem cell extract (MFSCE), which is a component of adipose-tissue-derived stem cells, on cognitive impairment in Aβ25–35-injected AD mice. The ICR mice were i.c.v. injected with Aβ25–35 and then treated with MFSCE for 14 days (i.p.). The Aβ25–35-injected mice showed deficits in spatial and object perception abilities, whereas treatment with MFSCE inhibited Aβ25–35-induced learning and memory impairment in the T-maze, novel object recognition, and Morris water maze tests. Moreover, Aβ25–35-induced lipid pe-roxidation and nitric oxide overproduction were attenuated by treatment with MFSCE. These anti-oxidant effects of MFSCE were related to the inhibition of the apoptotic signaling pathway. In par-ticular, the combination treatment of MFSCE and pyridoxal 5′-phosphate (PLP) showed greater suppression of Bax and cleaved caspase-3 protein expression compared to the MFSCE-or PLP-only treatment. Furthermore, the MFSCE and PLP combination significantly downregulated the amyloi-dogenic-pathway-related protein expressions, such as amyloid precursor protein, presenilin 1, and presenilin 2. Therefore, the MFSCE and PLP combination may synergistically prevent Aβ25–35-in-duced neuronal apoptosis and amyloidogenesis, which contributes to cognitive improvement and has potential therapeutic implications for AD patients.