Chaihu Oral Liquid improves hippocampal neurogenesis and short-term memory defects in adult BTBR autism mice

Abstract

Objective To investigate the effects of Chaihu Oral Liquid (CHOL) on the neurogenesis in hippocampal dentate gyrus (DG) and short-term memory defects in BTBR T+ Itpr3tf/J (BTBR) autism model mice. Methods Healthy adult male C57BL/6J(C57) mice (7~8 weeks old, 24.72±1.35 g) and BTBR mice (7~ 8 weeks old, 27.7±1.42 g) were randomly divided into groups as follows (n=4 in each group): C57 control, C57 drug treatment, BTBR control, and BTBR drug treatment. Mice in the treatment groups were given CHOL solution gavage (10 μL/g) once a day for 7 consecutive days, while those of the control group received equal volume of normal saline. Daily changes of body weight were recorded. After the last administration, hair grooming, bead embedding, new object recognition and open field experiments were conducted on the next day and lasted for 4 d. Finally, the samples of mice brain tissue were harvested, and immunofluorescence staining was performed to detect the NeuN, DCX, SOX2/GFAP labeled nerve cells in hippocampal DG. Results Behavioral results suggested that mice in the BTBR control group showed a more obvious preference for old objects in the new object recognition experiment (P < 0.01), as compared with the C57 control group, while the new object recognition index was significantly improved in the BTBR drug treatment group (P < 0.05). Moreover, the BTBR control group presented more repetitive behavior and longer movement distance than the C57 control during the hair grooming, bead embedding and open field experiments, as well as higher body weight (P < 0.05), whereas the BTBR treatment group had no significant changes in comparison with the BTBR control regarding these aspects. There were no notable differences between the C57 control and C57 treatment groups in terms of new object recognition index, repetitive behavior, motor ability and body weight. Immunofluorescence staining results indicated that the numbers of NeuN labeled mature neurons and DCX labeled newborn neurons in hippocampal DG were greatly decreased in the BTBR control group, so as the number of SOX/GFAP labeled neural progenitor cells (P < 0.01), while the number of neurocytes was remarkably increased in the BTBR drug treatment group (P < 0.05). There were no significant differences in the numbers of NeuN, DCX and SOX2/GFAP labeled neurocytes between the C57 control and the C57 treatment groups. Conclusion CHOL promotes the generation of hippocampal DG nerve progenitor cells, new and mature neurons in adult BTBR mice, and improves the short-term learning and memory dysfunction.

Keywords

• chaihu oral liquid
• autism
• neurogenesis
• hippocampus
• mice