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

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.

The effect of depression on the thermal nociceptive thresholds in rats with spontaneous pain

Objective Recently,there has been growing interest in the interaction between depressive disorders and pain.The purpose of this study was to examine whether depression would lead to a decreased sensitivity to noxious stimuli in rats with spontaneous pain.Methods The olfactory bulbectomized rats were used as a model of depression.The depression-like behaviors were assessed by open field test and changes in body weight.Formalin solution was injected into the rat hindpaw to produce ongoing pain.Noxious thermal stimuli were applied onto the hindpaw contralateral to formalin injection,and the withdrawal thresholds were measured.Results In non-depressive rats,the formalin-treated paw developed hypoalgesia to noxious stimuli while the contralateral paw was not affected.The depressive rats,however,showed a significantly lower sensitivity to noxious thermal stimulus,represented as higher withdrawal thresholds of the contralateral paw,when compared to the non-depressive rats.Conclusion These results demonstrate that depression can alleviate the stimulus-evoked pain even in the context of formalin inflammatory pain,consistent with the previous clinical observations that patients suffering from both depression and persistent pain have decreased sensitivities to noxious experimental stimuli.

Surface modification of PGP for a neutrophil–nanoparticle co-vehicle to enhance the anti-depressant effect of baicalein

Exploiting cells as vehicles combined with nanoparticles combined with therapy has attracted increasing attention in the world recently. Red blood cells, leukocytes and stem cells have been used for tumor immunotherapy, tissue regeneration and inflammatory disorders, and it is known that neutrophils can accumulate in brain lesions in many brain diseases including depression. N-Acetyl Pro–Gly–Pro(PGP) peptide shows high specific binding affinity to neutrophils through the CXCR2 receptor. In this study, PGP was used to modify baicalein-loaded solid lipid nanoparticles(PGP-SLNs) to facilitate binding to neutrophils in vivo. Brain-targeted delivery to the basolateral amygdala(BLA) was demonstrated by enhanced concentration of baicalein in the BLA. An enhanced anti-depressant effect was observed in vitro and in vivo. The mechanism involved inhibition of apoptosis and a decrease in lactate dehydrogenase release. Behavioral evaluation carried out with rats demonstrated that anti-depression outcomes were achieved. The results indicate that PGP-SLNs decrease immobility time, increase swimming time and climbing time and attenuate locomotion in olfactory-bulbectomized(OB) rats. In conclusion, PGP modification is a strategy for targeting the brain with a cell–nanoparticle delivery system for depression therapy.