Dysfunction of the BDNF-TrkB signaling pathway contributes to learning
and memory impairments induced by neuroinflammation in mice
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.