Objective       To investigate whether valproic acid (VPA) can affect autonomic activity and cerebral morphology and structure in the APP/PS1 double transgenic Alzheimer’s disease(AD) mouse model

so as to explore the neuroprotective effect of VPA on AD.       Methods      Three-month old APP/PS1 double transgenic AD model mice and its wild-type littermates were randomly divided into two groups (VPA-treated group and saline-treated group)

VPA [30 mg/（kg·d）] and the same amount of normal saline were peritoneally injected into mice for 4 weeks. Open field test was used to examine autonomous behaviors of AD model and wildtype mice. Nissl staining and transmission electron microscopy (TEM) were applied to observe the morphological structures in the brains of AD model mice.       Results      Open field test revealed that the autonomic activities of AD mice showed an obvious decrease when compared to wild-type mice (P0.05)

the autonomic activities of VPA-treated mice were decreased significantly compared with the saline-treated controls (P0.05)

while the autonomic activities of both VPA-treated and saline-treated wild-type mice showed no difference. Nissl staining showed that neuronal cells in the brain of AD model mice were greatly decreased compared with wild-type mice. Furthermore

neuronal cells in the brain of saline-treated AD model mice were severely reduced in number（85.2±13.3）

and a large number of neurons became swollen and round

the nuclei were slightly stained

and  the cytoplasm was pale in which Nissl bodies were reduced significantly. Administration of VPA notably suppressed the enhanced neuronal swelling and rescued the neuronal loss（116.9±16.2

P0.05）. VPA did not exert effect on the morphology and number of neuronal cells in the brain of both saline-treated and VPA-treated wildtype mice（142.2±24.4 vs 136.7±23.1

P0.05）. TEM revealed that the cytoplama

nucleus

part of mitochondria and neuropil in AD mice became obviously swollen

which were partially rescued by VPA. Meanwhile

the structure of synapse became clearer in VPA-treated mice.       Conclusion      VPA reduces the autonomous behavior and relieves manic symptoms in AD model mice. VPA may not only change the morphology of neuronal cells

but also rescue the neuronal loss in the brains of AD model mice.