The BDNF-TrkB signaling pathway and its downstream cascade disorders participate in learning and memory impairments. The BDNF - TrkB signaling pathway and its downstream cascades are involved in the generation of synapses which then regulate learning and memory. Intraperitoneal injection of LPS damages the BDNF - TrkB signaling pathway and its downstream cascade, leading to cognitive dysfunction. 7,8-DHF can penetrate the blood–brain barrier and activate TrkB receptors, alleviating learning and memory deficits. [Display omitted] • The BDNF-TrkB pathway and downstream cascades are involved in cognitive deficits. • 7,8-DHF could alleviate cognitive deficits via acting on the TrkB in LPS mice. • The mPFC, hippocampus and EC regions are associated with learning and memory. • 7,8-DHF might serve as a potential treating target in neurodegenerative diseases. Accumulating evidence suggests that neuroinflammation is the main mechanism in cognitive dysfunction and that brain-derived neurotrophic factor (BDNF) is involved in learning and memory by binding to tyrosine kinase B (TrkB) receptors. Herein, we tested the roles of the BDNF - TrkB signaling pathway and its downstream cascade in lipopolysaccharide (LPS) induced cognitive dysfunction in mice. Mice were treated with LPS (0.25 mg/kg) for 7 days, and learning and memory function was evaluated by the novel object recognition test (NORT). Western blotting was performed to elucidate roles of the BDNF - TrkB signaling pathway and its downstream cascades in LPS mice. The NORT showed that LPS induced learning and memory deficits in mice. The levels of IL-1β, IL-6, and TNF-α in the serum and central nervous system decreased in LPS mice. In addition, LPS reduced the 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 hippocampus and medial prefrontal cortex regions. In the entorhinal cortex, the protein levels of BDNF, p-TrkB, Bcl-2, p-CaMK2 and p-CREB were decreased, and the protein level of Bax was increased in LPS mice. Interestingly, 7,8-DHF alleviated these disorders in LPS mice and improved learning and memory function; however, the TrkB antagonist ANA12 effectively reversed effects of 7,8-DHF. Therefore, we conclude that the BDNF - TrkB signaling pathway and its downstream cascades disorders in different regions are main mechanisms of cognitive dysfunction, and 7,8-DHF maybe useful as a new treatment for preventing or treating cognitive dysfunction induced by neuroinflammation in neurodegenerative diseases. [ABSTRACT FROM AUTHOR]