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

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Background 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. Methods 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 elucidated roles of the BDNF-TrkB signaling pathway and its downstream cascades in LPS mice. 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 medial prefrontal cortex (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 entorhinal cortex (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 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.