Increased expression of BDNF and proliferation of dentate granule cells after bacterial meningitis

Objectives: Proliferation and differentiation of neural progenitor cells is increased after bacterial meningitis. In order to identify endogenous factors involved in neurogenesis, expression of BDNF, NGF and GDNF was investigated in a mouse model of pneumococcal meningitis.

Methods: Male C57BL/6 mice were infected by injection of log 4 CFU of S. pneumoniae into the right forebrain. Control animals received saline only. Mice were killed 30 hours later (each group n=19) or treated with Ceftriaxone (100mg/kg twice daily) and sacrificed 4 days after infection (each group n=19). Gene expression levels of neurotrophins were measured by real-time pcr and BDNF protein synthesis was determined by western blot. Immunohistochemistry was performed for BDNF, TrkB, NeuN, Calbindin and BrdU.

Results: Four days after infection, hippocampal BDNF mRNA levels were increased 2.4-fold (p=0.026). Similarly, BDNF protein levels in the hippocampal formation were higher in infected mice compared to control animals (p=0.0003). This was accompanied by an elevated proliferation of dentate granule cells as indicated by BrdU-incorporation (p=0.0002). BDNF protein was located predominantly in the hippocampal CA3/4 area and the hilus. The density of dentate granule cells expressing the BDNF receptor TrkB was increased 4 days after infection (p=0.027). Similarly, TrkB mRNA levels were increased in the hippocampal formation. Conversely, NGF mRNA levels at 30 hours after infection were reduced by approximately 50% (p=0.004). No significant changes in GDNF expression were observed.

Conclusion: The increased gene expression and protein synthesis of BDNF and its receptor TrkB suggests a contribution of this neurotrophic factor to neurogenesis after bacterial meningitis.