Treadmill exercise counteracts the suppressive effects of peripheral lipopolysaccharide on hippocampal neurogenesis and learning and memory

Abstract

New neurons are continuously generated in hippocampal subgranular zone throughout life, and the amount of neurogenesis is suggested to be correlated with the hippocampusdependent function. Several extrinsic stimuli are known to modulate the neurogenesis process. Among them, physical exercise has advantageous effects on neurogenesis and brain function, while inflammation shows the opposite. Herein we showed that a moderate running exercise successfully restored the peripheral lipopolysaccharide (LPS)-impaired neurogenesis in the dentate area. LPS treatment obstructed neuronal differentiation, but not proliferation. Exercise training facilitated both the proliferation of the neural stem cells and their differentiation into neurons. Interestingly, exercise replenished the LPS-reduced levels of brain-derived neurotrophic factor and its receptor, TrkB, and rescued the LPSdisturbed performance in water maze; while the LPS-elicited up-regulation of tumor necrosis factor-alpha and interleukin1b remained unaltered. In conclusion, our findings suggest that running exercise effectively ameliorates the LPS-disturbed hippocampal neurogenesis and learning and memory performance. Such advantageous effects of running exercise are not due to the alteration of inflammatory response, but possibly by the restoring the LPS-lessened brain-derived neurotrophic factor signaling pathway.

Neonatal Peripheral Immune Challenge Activates Microglia and Inhibits Neurogenesis in the Developing Murine Hippocampus

“…Experimentally, systemic inflammation as induced by intraperitoneal administration of the Gram-negative bacterium-derived lipopolysaccharide (LPS) [19,20,21,22,23,24] or subcutaneous administration of Escherichia coli [25,26,27] has been shown to upregulate proinflammatory cytokine production and increase microglial activation in the rodent CNS. Furthermore, neonatal induction of central inflammation by subcutaneous E. coli administration reduces adult performance in hippocampus-dependent memory tasks, but only if a second peripheral LPS immune challenge is given in close temporal proximity to the test-learning phase [25], an effect attributed to reduced hippocampal neurogenesis [27].…”

Sick and Tired: Mood, Fatigue, and Inflammation in Cancer

“…• Decreased neurogenesis in the hippocampus, decreased hippocampal BDNF, and increased hippocampal TNF-α and IL-1beta were observed in LPS treated animals [51].…”

“…Indeed, meta-analyses have demonstrated that serum BDNF is low in depressed patients (not taking antidepressants) compared to healthy controls and that serum BDNF levels increase with antidepressant treatment [50]. Studies have demonstrated that PICs may impact levels of neurotrophic factors [51]. See Table 1.…”

Comparison of hippocampal interleukin-6 immunoreactivity after exhaustive exercise in both exercise-trained and untrained rats

“…In recent years, there have been many studies published on the proinflammatory functions of the cytokine IL-6 in the pathogenesis of several neurodegenerative disorders. However, due to the pleiotropic functions (acting both as a proinflammatory and an antiinflammatory) of IL-6, it is thought that the production of a determined level of IL-6 during moderate exercise can reverse the detrimental effects of uncontrolled inflammation by triggering the antiinflammatory effects of other cytokines (30). In an animal model showing the death of the hippocampal dentate granule cell layer after a chemical application, exercise attenuated neuronal death and diminished the elevation of the level of TNF-α, but this effect was undetectable in IL-6 knock-out mice (31).…”