Intranasal Administration of Conditioned Medium from Cultured Mesenchymal Stem Cells Improves Cognitive Impairment in Olfactory Bulbectomized Mice

Kazuhiro Kojima,Sei-Ichi Yoshihara,Katsuyuki Oki,Ichiro Kawahata,Kohji Fukunaga,Hisanao Izumi

doi:10.4236/aad.2020.93004

Abstract

Alzheimer’s disease (AD) is the common cause of dementia which shows the neuro-pathologies like an accumulation of amyloid-β (Aβ) and degeneration of cholinergic neuron. Olfactory bulbectomized (OBX) mice show some of AD features, so they have been used to research as AD model. Mesenchymal stem cells (MSCs) can differentiate into many kinds of cells, including neuronal cells. In this study, we intranasally administrated the conditioned medium derived from cultured umbilical cord (UC) MSCs. The intranasal administration of the MSCs medium restored the cognitive impairment observed in OBX mice. In addition, the decreased number of choline acetyltransferase-positive cells in the medial septum was restored by the conditioned medium administration. In conclusion, MSCs-derived conditioned medium may have protective effects of cholinergic neurons in the medial septum, thereby rescuing the cognitive impairment of OBX.

Highlights

Alzheimer’s disease (AD) is a common disorder associated with cognitive impairment
We further showed that ST101 treatment improved memory impairment associated with the increased phosphorylation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) and protein kinase C (PKC) in the hippocampus via activation of T-type voltage-gated calcium channel [10] [11]
We demonstrated that conditioned medium derived from cultured umbilical cord (UC) Mesenchymal stem cells (MSCs) potently restored cognition impairment in OBX mice

Summary

Introduction

Alzheimer’s disease (AD) is a common disorder associated with cognitive impairment. AD is characterized by amyloid-β (Aβ) plaque and intracellular neurofibrillary tangles (NFTs) [1]. Those medicines can only prevent the progression of AD’s symptoms and not be able to cure them fundamentally. Β-secretase inhibitor and anti-Aβ antibody are received attention for new therapeutic agents, but these compounds have not succeeded in recovering AD symptoms yet [2] [3] [4] [5] [6]

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Conclusion