Effects Of Schisandrin A And B On Neurogenesis In The Subventricular Zone Of Adult Mouse Brain

Schisandra is one of the well-known traditional Chinese herb medicines, which hasbeen used more than2,000years medically. It is reported that Schisandra is beneficialto brain, mental, and aging. Schisandrin A (Sch A) and Schisandrin B (Sch B) are therepresentative lignans extracted from Schisandra chinensis. Although the positiveeffects of Sch A and B on the nervous system have been well-known, the effectmechanisms on the neurogenesis in the subventricular zone of adult mouse brain arestill unclear.In the adult brain, there are two neurogenic regions to generate new neurons: thesubventricular zone (SVZ) of lateral ventricles and the subgranular zone (SGZ) ofhippocampus. The neural stem cells (NSCs) in these regions have the potential ofself-renewal and differentiation and they also have the capability of response todisease and injury. The NSCs in the SVZ primarily give rise to transit-amplifyingcells and the latter differentiate into neuroblasts after several rapid divisions. Theneuroblasts migrate tangentially along the rostral migratory stream (RMS) towards theolfactory bulb (OB), and then migrate radically to the granular cell layer (GCL) andperiglomerular layer (GL), where they differentiate into granule cells (GCs) andperiglomerular cells (PGc) and the majority of them differentiate into functionalinterneuron and play a role in the local neural network.In this study, a preliminary analysis to determine an optimal dosage of Sch A and Bwas firstly performed. As a result, the groups of Sch A and Sch B with10mg/kg·ddosage were much better than the other two dosages. It indicated that the effects ofSch A and B on the neurogenesis were not dosage-dependent. Thus,10mg/kg·ddosage was administrated in the subsequent experiments. In the followingexperiments, the phospho histone H3(PHH3) was used to label the proliferating cells to analyze the effects of Sch A and B on cell proliferation in the SVZ, RMS and OB.The results showed that the number of PHH3+cells was significantly increasing in theSVZ for Sch B treatment (P<0.01). In the RMS and OB, however, the number ofPHH3+cells in the group of Sch A and B was unchanged. These results indicate thatSch B instead of Sch A can promote cell proliferation in the brain of adult mouse. Toexamine whether the amounts of NSCs and neuroblasts in the SVZ were altered, theglial fibrillary acidic protein (GFAP) and doublecortin (Dcx) were labeledrespectively. Statistical analysis showed that the intensity of GFAP+cell of the Sch Bgroup had a significant increase (P<0.05), while no significance for the Sch Atreatment. The fluorescent intensity of Dcx+cells of Sch A or B in the SVZ also hadno change. To elucidate the impacts of Sch A and B on the formation of migrationneuroblasts, Dcx was used to labeled the neuroblasts to detect the fluorescenceintensity. A significant improvement was observed in the result of the intensity ofDcx+neuroblasts in the Sch A group compared to the controls (P<0.01), while Sch Bhad almost no effect on the neuroblasts formation, suggesting that Sch A can increasethe formation of neuroblasts in the RMS. At last, the PG cells and all the cells in theOB were respectively labeled with calbindin (CalB)/tyrosine hydroxylase (TH) andcalretinin (CalR). The results showed that Sch B can increase the number of CalB+and CalR+cells (P<0.05), while Sch A obviously lowered the number of CalB+andTH+cells (P<0.05).In summary, Sch B can stimulate the neurogenesis in the adult brain by promotingthe proliferation of neuronal cells and the survival of interneurons. Although it plays arole in the course of cell formation, Sch A has an inhibitory effect on the neurogenesis.These results suggest that Sch B can protect neuronal cells and prevent theneurodegenerative diseases by positive modulation of neurogenesis in the adult SVZ.