Effects of Xiangshao granules on behavior and OPCs and OLs in the medial prefrontal cortex of mice with post-stroke depression / 中华神经医学杂志

ABSTRACT

Objective:To investigate the effects of Xiangshao granules on behavior and oligodendrocyte precursor cells (OPCs) and oligodendrocytes (OLs) in the medial prefrontal cortex (mPFC) of post-stroke depression (PSD) mice.Methods:Eighty C57BL/6 mice were divided into sham-operated group, middle cerebral artery occlusion (MCAO) group, PSD+PBS group, and PSD+Xiangshao group ( n=20). PSD models were constructed using mild chronic unforeseeable stress (CUMS) and solitary feeding after MCAO. MCAO models were evaluated by laser speckle contrast imaging (LSCI), modified neurological severity score (mNSS) and TTC staining. PSD models were evaluated by body mass, sugar and water preference test and tail suspension test. After PSD modeling, mice in the sham-operated group, MCAO group, and PSD+PBS group were given 0.2 mL PBS, while mice in the PSD+Xiangshao group was given Xiangshao granules at dosage of 60 mg/kg (dissolved in 0.2 mL PBS); all were given via intragastric administration once a d for 28 d. Number of OPCs and OLs in mPFC was detected by immunofluorescence. Expressions of myelin basic protein (MBP) and phosphatidylinositol 3-kinase/serine/threonine kinase/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway proteins in mPFC were detected by Western blotting. Results:(1) Model verification results: LSCI showed obvious changes of cerebral blood flow in the middle cerebral artery supply area before, during and after MCAO; TTC staining showed typical red non-infarct area and white infarct area in MCAO group, PSD+PBS group and PSD+ Xiangshao group; mNSS scores in MCAO group, PSD+PBS group and PSD+ Xiangshao group were all >4, without significant differences ( P>0.05); the MCAO model was successfully constructed. After PSD and before treatment, the PSD+PBS group and PSD+Xiangshao group had significantly decreased body weight and sugar-water preference, and statistically prolonged tail suspension immobilization time compared with sham-operated group and MCAO group ( P<0.05); the PSD model was successfully constructed. (2) Results of mouse behavior experiment after treatment: significant differences in body weight, sugar-water preference and tail suspension time were noted in mice of the 4 groups 28 d after treatment ( P<0.05); PSD+Xiangshao group had significantly increased body weight and sugar-water preference and decreased tail suspension immobilization time compared with PSD+PBS group ( P<0.05). (3) Number of OPCs (Olig2 +PDGFRa +), proliferative OPCs (Ki-67 +PDGFRa +, EdU +PDGFRa +) and OLs (Olig2 +CC1 +), and relative MBP, p-PI3K, p-AKT and p-mTOR protein expressions in mPFC of the 4 groups were significantly different ( P<0.05); compared with those in PSD+PBS group, the above cell number and relative protein expressions in PSD+Xiangshao group were significantly increased ( P<0.05). Conclusion:Xiangshao granules can promote the OPCs proliferation and OLs maturation by activating PI3K/AKT/mTOR signaling pathway in mPFC, thus playing a role in PSD.