Abstract
Regulation of adult neurogenesis plays an important role in therapeutic strategies for various neurodegenerative diseases. Recent studies have suggested that the enhancement of adult neurogenesis can be helpful in the treatment of Parkinson’s disease (PD). In this study, we investigated whether Korean red ginseng (KRG) can enhance neurogenesis in the subventricular zone (SVZ) of a PD mouse model. To accomplish this, male 8-week-old C57BL/6 mice were injected with vehicle or 20 mg/kg of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) four times at 2 h intervals. After the final injection, they were administered water or 100 mg/kg of KRG extract and injected intraperitoneally with 50 mg/kg of 5’-bromo-2’-deoxyuridine-monophosphate (BrdU) once a day for 14 consecutive days. After the last pole test, dopaminergic neuronal survival in the striatum and the substantia nigra (SN), cell proliferation in the SVZ and mRNA expression of neurotrophic factors and dopamine receptors in the striatum were evaluated. KRG administration suppressed dopaminergic neuronal death induced by MPTP in the striatum as well as the SN, augmented the number of BrdU- and BrdU/doublecortin (Dcx)-positive cells in the SVZ and enhanced the expression of proliferation cell nuclear antigen, brain derived neurotrophic factor (BDNF), glial cell derived neurotrophic factor (GDNF), cerebral dopamine neurotrophic factor (CDNF), ciliary neurotrophic factor (CNTF), dopamine receptor D3 (DRD3) and D5 mRNAs. These results suggest that KRG administration augments neurogenesis in the SVZ of the PD mouse model.
Highlights
Adult neurogenesis is the process through which functional, mature neurons are formed from adult neural precursors in specific brain regions, the subventricular zone (SVZ) and the subgranular zone (SGZ) in mammals (Ming and Song, 2011)
On day 14, the descending time in the MPTP group was significantly higher than those in the other three groups (p < 0.05 in each group), but the times were not significantly different among the vehicle-injected and water-treated control group (Veh), MPTP and MPTP+Korean red ginseng (KRG) groups (Figure 1). These results indicate that MPTP injection induces motor dysfunction, but KRG administration can alleviate it
This study demonstrated that KRG administration alleviated MPTP-induced behavioral dysfunction and increased cell differentiation and proliferation of neural stem cell (NSC) in the SVZ of MPTP-treated mice
Summary
Adult neurogenesis is the process through which functional, mature neurons are formed from adult neural precursors in specific brain regions, the subventricular zone (SVZ) and the subgranular zone (SGZ) in mammals (Ming and Song, 2011). The regulation of adult endogenous neurogenesis plays an important role in therapeutic strategies for various neurodegenerative conditions such as Parkinson’s disease (PD), Alzheimer’s disease and stroke (Geraerts et al, 2007; Ryu et al, 2016b) because adult neurogenesis may act as an endogenous repair mechanism in the adult brain (Ming and Song, 2011). It has been suggested that neurotransmitters and neurotrophic factors play an important role in the regulation of endogenous neurogenesis (Abdipranoto et al, 2008). Increases in brain derived neurotrophic factor (BDNF) have been found to enhance endogenous neurogenesis in the SVZ and the SGZ (Zhao et al, 2008), while the release of neurotrophic factors such as glial cell-derived neurotrophic factor (GDNF) has been shown to promote neurogenesis and synaptic connectivity (Borta and Höglinger, 2007). In addition to neurotrophic factors, dopamine receptor D3 (DRD3) and dopamine receptor D5 (DRD5) are known to be involved in adult neurogenesis as well as the pathophysiology of PD (Borta and Höglinger, 2007; Chen et al, 2013; Chetrit et al, 2013; Lao et al, 2013; Elgueta et al, 2017)
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