Salidroside induces rat mesenchymal stem cells to differentiate into dopaminergic neurons

Abstract

Parkinson’s disease (PD) is a neurodegenerative disorder characterised by the loss of substantia nigra dopaminergic neurons that leads to a reduction in striatal dopamine (DA) levels. Replacing lost cells by transplanting dopaminergic neurons has potential value to repair the damaged brain. Salidroside (SD), a phenylpropanoid glycoside isolated from plant Rhodiola rosea, is neuroprotective. We examined whether salidroside can induce mesenchymal stem cells (MSCs) to differentiate into neuron-like cells, and convert MSCs into dopamine neurons that can be applied in clinical use. Salidroside induced rMSCs to adopt a neuronal morphology, upregulated the expression of neuronal marker molecules, such as gamma neuronal enolase 2 (Eno2/NSE), microtubule-associated protein 2 (Map2), and beta 3 class III tubulin (Tubb3/β-tubulin III). It also increased expression of brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and nerve growth factor (NGF) mRNAs, and promoted the secretion of these growth factors. The expression of dopamine neurons markers, such as dopamine-beta-hydroxy (DBH), dopa decarboxylase (DDC) and tyrosine hydroxylase (TH), was significantly upregulated after treatment with salidroside for 1–12 days. DA steadily increased after treatment with salidroside for 1–6 days. Thus salidroside can induce rMSCs to differentiate into dopaminergic neurons.

Influence of salidroside, a neuroactive compound of Rhodiola rosea L., on alcohol tolerance development in rats

“…The results of other studies, both in vitro and in vivo, also indicate the ability of Sal to affect the activity of nervous system. Zhao et al [36], for example, revealed that Sal was able to make rat mesenchymal stem cells (MSCs) to differentiate into dopaminergic neurons. Focal cerebral ischemia-reperfusion injury in rat model was protected by Sal pretreatment possibly involving its ability to reduce the permeability of blood brain barrier [15,20].…”

Intracarotid Infusion of Mesenchymal Stem Cells in an Animal Model of Parkinson's Disease, Focusing on Cell Distribution and Neuroprotective and Behavioral Effects

“…A potential explanation for this phenomenon may involve the recognized ability of rMSCs to secrete regulatory and trophic factors. Brain‐derived neurotrophic factor (BDNF), in particular, is constitutively synthesized and released by MSCs, which maintain this ability after transplantation [14, 29, 85, 86]. BDNF is a key regulator of neural circuit function and is involved in the modulation of synaptic function by changing either the efficacy of presynaptic transmitter release or the magnitude of postsynaptic responses [87].…”

Conditioned Medium Derived from Salidroside-Pretreated Mesenchymal Stem Cell Culture Ameliorates Mouse Lipopolysaccharide-Induced Cerebral Neuroinflammation- Histological and Immunohistochemical Study

“…Each 24-well plate was divided equally (12 wells) into CM and CM-Sal in which the latter was exposed to 100 μ g/mL salidroside (purity ≥95% (LC/MS-ELSD), Sigma–Aldrich, MO, USA) for 48 h of culture (10). Then CM and CM-Sal were collected separately, and centrifuged at 1500 rpm for 5 min.…”

“…Previous studies showed that Sal could induce rat MSCs to differentiate into cholinergic neurons (9) and dopaminergic neurons (10). Concurrently, Sal has been reported to exert anti-inflammatory and neuroprotective effects on cultured murine microglial cells (1).…”