Abstract
Background and Purpose:Evidence suggests neuroinflammation is the main mechanism in cognitive
dysfunction. The brain-derived neurotrophic factor (BDNF) is involved in
learning and memory via binding to tyrosine kinase B (TrkB) receptors.
Herein, we mainly tested roles of the BDNF-TrkB signaling pathway and
its downstream cascades in lipopolysaccharide (LPS) induced cognitive
dysfunction in mice.
Experimental Approach: Mice were treated with LPS and 7,8-DHF
for 7 days, and learning and memory function was evaluated by the novel
object recognition test (NORT). Western blot and enzyme-linked
immunosorbent assay (ELISA) elucidated roles of the BDNF-TrkB signaling
pathway and its downstream cascades in LPS mice.
Key Results: The NORT showed that LPS induced learning and
memory deficits in mice. LPS increased the levels of IL-1β, IL-6, and
TNF-α in the serum of mice. In the hippocampus and mPFC regions, LPS
reduced protein levels of BDNF, p-TrkB, Bcl-2, p-ERK1/2, p-CaMK2, p-CREB
and p-GluR1 and increased the expression of Bax. In the EC, levels of
BDNF, p-TrkB, Bcl-2, p-CaMK2 and p-CREB proteins were reduced and the
protein level of Bax was increased in LPS mice. 7,8-DHF could alleviate
these disorders in LPS mice and improved their learning and memory
function, however, the TrkB antagonist ANA12 effectively reversed the
effects of 7,8-DHF.
Conclusion and Implications: These results revealed that the
BDNF-TrkB signaling pathway and its downstream cascades disorders
contributed to neuroinflammation induced cognitive dysfunction in mice.
7,8-DHF could become a new therapeutic drug for cognitive dysfunction
induced by BDNF-TrkB signaling pathway disorders in neurodegenerative
diseases.