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Sodium Butyrate Prevents Memory Impairment by Re-establishing BDNF and GDNF Expression in Experimental Pneumococcal Meningitis

Abstract

Pneumococcal meningitis is a serious infection of the central nervous system (CNS) with high fatality rates that causes reduced psychomotor performance, slight mental slowness, impairments in attention executive functions and learning and memory deficiencies. Previously, we demonstrated a correlation between memory impairment and decreased levels of brain-derived neurotropic factor (BDNF) in the hippocampi of rats subjected to pneumococcal meningitis. Emerging evidence demonstrates that histone acetylation regulates neurotrophins; therefore, a potential molecular intervention against cognitive impairment in bacterial meningitis may be the histone deacetylase (HDAC) inhibitor, sodium butyrate, which stimulates the acetylation of histones and increases BDNF expression. In this study, animals received either artificial cerebrospinal fluid as a placebo or a Streptococcus pneumoniae suspension at a concentration of 5 × 109 colony-forming units (CFU/mL). The animals received antibiotic treatment as usual and received saline or sodium butyrate as an adjuvant treatment. Ten days after, meningitis was induced; the animals were subjected to open-field habituation and the step-down inhibitory avoidance task. Immediately after these behavioural tasks, the animals were killed, and their hippocampi were removed to evaluate the expression of BDNF, nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF). In the meningitis group that received saline, the animals presented memory impairment in both behavioural tasks, and hippocampal BDNF and GDNF expression was decreased. Sodium butyrate was able to prevent memory impairment and re-establish hippocampal neurotrophin expression in experimental pneumococcal meningitis.

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Acknowledgments

The Laboratory of Experimental Microbiology and Laboratory of Neurosciences (Brazil) are centres of the National Institute for Translational Medicine (INCT-TM) and members of the Center of Excellence in Applied Neurosciences of Santa Catarina (NENASC). This research was supported by grants from CNPq (JQ and TB), FAPESC (JQ and TB), Instituto Cérebro e Mente (JQ and TB) and UNESC (JQ and TB). JQ and TB are CNPq Research Fellows. JSG and LRS are holders of a CAPES studentship.

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The authors declare that they have no conflict of interest.

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Correspondence to Tatiana Barichello.

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Barichello, T., Generoso, J.S., Simões, L.R. et al. Sodium Butyrate Prevents Memory Impairment by Re-establishing BDNF and GDNF Expression in Experimental Pneumococcal Meningitis. Mol Neurobiol 52, 734–740 (2015). https://doi.org/10.1007/s12035-014-8914-3

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  • DOI: https://doi.org/10.1007/s12035-014-8914-3

Keywords

  • Pneumococcal meningitis
  • Sodium butyrate
  • BDNF
  • GDNF
  • NGF
  • Memory