Spermine protects from LPS-induced memory deficit via BDNF and TrkB activation

Abstract

Lipopolysaccharide (LPS) has been long known to promote neuroinflammation and learning and memory deficits. Since spermine, one of the main natural polyamines in the central nervous system, protects from LPS-induced memory deficit by a mechanism that comprises GluN2B receptors, the aim of the present study was to determine whether brain-derived neurotrophic factor (BDNF), tropomyosin-related kinase B (TrkB) receptor and cAMP response element binding (CREB) are involved in this protective effect of spermine. Adult male Swiss albino mice received, immediately after training in the novel object recognition task, saline or LPS (250 μg/kg, i.p.); 5 min later they received saline or spermine (0.3 mg/kg, i.p.) and, when specified, 5 min thereafter saline or the TrkB receptor antagonist ANA-12 (0.5 mg/kg, i.p.) in different flanks. Animals were tested 24 h after training. Spermine protected from LPS-induced memory deficit and this protective effect was reversed by ANA-12. In a subset of animals BDNF, CREB and phospho-CREB immunoreactivity was determined in the hippocampi and cerebral cortex 4 h after spermine injection. Spermine reversed the decrease of mature BDNF levels induced by LPS in both hippocampus and cerebral cortex. Spermine increased phospho-CREB content and phospho-CREB/total CREB ratio in the cerebral cortex of LPS-treated mice. The results support that the protective effect of spermine on LPS-induced memory deficits depends on TrkB receptor activation and is accompanied by restoration of mature BDNF levels in hippocampus and cerebral cortex, as well as increased CREB phosphorylation in the cerebral cortex.

Developmental Exposure to Atrazine Impairs Spatial Memory and Downregulates the Hippocampal D1 Dopamine Receptor and cAMP-Dependent Signaling Pathway in Rats

“…We thus proposed that ATR exposure may only influence the phosphorylation of CREB in the hippocampus. These results are consistent with those of previous studies suggesting that the cAMP-dependent signaling pathway and its downstream molecules were affected by other hippocampal toxicants, such as amyloid-beta peptide, aluminum, and lipopolysaccharides [47,48,49,50]. Collectively, our findings suggest that developmental exposure to ATR impaired the spatial memory capabilities of rats, altered the ultrastructure of hippocampal neurons and downregulated the D1DR as well as the cAMP-PKA-CREB signaling pathway in the hippocampus.…”

Interplay Between Human Gut Bacteria Escherichia coli and Lactobacillus mucosae in the Occurrence of Neuropsychiatric Disorders in Mice

“…Excessive IL-6 and corticostrone expression was increased by stressors such as immobilization and pathogen infection via the activation of the HPA axis. Treatment with therapeutic drugs for psychiatric disorders reduces blood IL-6 and corticosterone levels, increases BDNF expression, and alleviates neuropsychiatric disorders (10,11,30). Treatment with corticosterone suppresses BDNF expression in SH-SY5Y cells in vitro and in mice.…”

The Role of BDNF in the Neuroimmune Axis Regulation of Mood Disorders

“…The significant reduction in BDNF was caused by the administration of pro-inflammatory cytokines or lipopolysaccharide (LPS), an inducer for cytokines, serve as an example. LPS injections could significantly reduce mature BDNF levels in the hippocampus and cerebral cortex (118), as well as IFN-α administration, which decreased systemic BDNF levels (119). Furthermore, other neurotrophic factors also decreased to varying degrees: NGF and neurotrophic factor−3 (NT-3), for instance (120).…”