Neuroprotective effects of novel compound FMDB on cognition,
neurogenesis and apoptosis in APP/PS1 transgenic mouse model of
Alzheimer’s disease
Abstract
Background and Purpose Clinical and experimental studies have shown that
the sharp reduction of estrogen is one of the important reasons for the
high incidence of Alzheimer’s disease (AD) in elderly women, but there
is currently no such drug for treatment of AD. Our group first designed
and synthesized a novel compound named FMDB. In this study, our aim is
to investigate the neuroprotective effects and mechanism of FMDB in
APP/PS1 transgenic mice. Experimental Approach 6 months old APP/PS1
transgenic mice were intragastrically administered with FMDB (1.25mg/kg,
2.5mg/kg and 5 mg/kg) every other day for 8 weeks. LV-ERβ-shRNA was
injected bilaterally into the hippocampus of APP/PS1 mice to knockdown
ERβ. Morris water maze test, novel object recognition test and open
field test were used to evaluate the cognitive function.
Immunofluorescence, TUNEL staining and Western Blot analysis were used
for evaluating the hippocampal neurogenesis, apoptosis and signal
transduction pathway related proteins. Key Results We found that FMDB
ameliorate cognitive impairment in the Morris water maze and novel
object recognition tests, increase hippocampal neurogenesis and prevent
hippocampal apoptotic responses in APP/PS1 mice. Importantly, FMDB
activated nuclear ERβ mediated CBP/p300, CREB and BDNF signaling, and
membrane ERβ mediated PI3K/Akt, CREB and BDNF signaling in the
hippocampus. Conclusion and Implications Our study demonstrates the
contributions and mechanism of FMDB to cognition, neurogenesis and
apoptosis in APP/PS1 mice. These lay the experimental foundation for the
development of new anti-AD drugs.