Neuroprotective effect of Liu Wei Di Huang Tang on adult hippocampal neurogenesis in mice / 中国药理学与毒理学杂志

ABSTRACT

OBJECTIVE To explore the effect and mechanisms of LW-AFC,a new formula derived from Liu Wei Di Huang Tang,on irradiation-induced reduction of mice adult hippocampal neurogenesis. METHODS C57BL/6J mice were randomly divided into seven groups (n=10) control group, LW-AFC group (1.6 g·kg-1), Liu Wei Di Huang Tang (LW) group (10 g·kg-1), brain derived neurotrophic factor (BDNF) group, irradiation group, irradiation+LW group, and irradiation+LW-AFC group. Reduction of mice adult hippocampal neurogenesis was induced by cranial irradiation.LW-AFC was administered by oral gavage for 30 d after cranial irradiation treatment. Immunofluorescence and Nissl′s staining were performed for histological morphology assessment. Bromodeoxyuridine (BrdU) staining was used in the detection of proliferation cells. The peripheral blood and hippocampal homogenate were collected to measure the content of tumor necrosis factor-α (TNF-α), interferon-gamma (INF-γ), interleukin-1β (IL-1β),IL-4 and IL-10.The hippocampal homogenate was used for Western blot to detect the BDNF-TrkB signal pathway, including extracellular regulated protein kinases1/2 (ERK1/2) and BDNF target protein. Morris water maze and new object recognition test were performed to examine the cognitive function of mice.The mice forced swimming and tail suspension test were used to assess alteration in depressive behavior. Long term potentiation was used to examine the synaptic plasticity change of mice. RESULTS Adult hippocampal neurogenesis was significantly reduced after irradiation of 20 Gray dose (10 Gray per day, total 2 d). LW-AFC treatment increased the BrdU number of irradiated mice (P<0.05). In Morris water maze test, LW-AFC group showed decreased escape latency in the learning period (P<0.05), while increased the number of crossing the platform in the memory period. LW-AFC can also reduce the immobility time of mice in the tail suspension test (P<0.01). CONCLU-SION LW-AFC modulates adult neurogenesis to ameliorate cognitive impairment and reduce depres-sive behavior in radiation injury mice.