ObjectiveTo investigate the effects of hippocampal aromatase (AROM) on spatial learning and memory

specific pathology and synaptic plasticity in APP/PS1 mouse model of Alzheimer’s disease (AD mice) and explore the underlying mechanisms. MethodsWestern blotting was used to detect the expression of AROM and androgen receptor in the hippocampus of male WT mice and AD mice at different months of age. Then

an overexpressed viral vector of AROM was constructed (oAROM) and injected stereotaxically into the hippocampus of 6-month-old AD mice.  3 months later

the spatial learning and memory abilities of the mice were studied with Morris water maze test. Western blot was employed to measure the changes of Aβ- and synapse-related proteins

and cytoskeleton regulatory proteins in the hippocampus. Immunohistochemical staining and immunofluorescence assay were used to detect the changes of Aβ. The changes of synaptic density and postsynaptic membrane thickness were observed with transmission electron microscopy. ResultsThe protein level of AROM was significantly decreased in WT mice of 10 months old (P<0.01)

but in the AD mice of only 6 months old (P<0.01). Compared with the APP/PS1 mice

the time in the target quadrant and the times crossing the platform were significantly increased in the oAROM mice (P<0.05). In the oAROM mice

the Aβ immunopositive materials were obviously decreased (P<0.01)

levels of Aβ producing protein and actin depolymerization protein were decreased

while Aβ degrading protein

selected synaptic proteins and actin polymerization protein were increased (P<0.01). Moreover

CA1 synaptic density (P<0.01) and postsynaptic membrane thickness (P<0.01) were significantly increased in the oAROM mice. What’s more

the expression of actin regulator Profilin-1 was significantly up-regulated (P<0.01) while Cofilin

a protein controlling dynamics of actin filaments

was significantly decreased (P<0.01). ConclusionHippocampus-specific overexpression of AROM can improve the synaptic plasticity and inhibit AD-related pathological changes in the hippocampus of dementia mice

and then improve the spatial learning and memory impairment

suggesting hippocampal AROM may be a novel target against AD.