Vitamin B6 reduces hippocampal apoptosis in experimental pneumococcal meningitis

Zysset-Burri, Denise C.; Bellac, Caroline L; Leib, Stephen L.; Wittwer, Matthias (2013). Vitamin B6 reduces hippocampal apoptosis in experimental pneumococcal meningitis. BMC infectious diseases, 13, p. 393. BioMed Central 10.1186/1471-2334-13-393

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BACKGROUND Bacterial meningitis caused by Streptococcus pneumoniae leads to death in up to 30% of patients and leaves up to half of the survivors with neurological sequelae. The inflammatory host reaction initiates the induction of the kynurenine pathway and contributes to hippocampal apoptosis, a form of brain damage that is associated with learning and memory deficits in experimental paradigms. Vitamin B6 is an enzymatic cofactor in the kynurenine pathway and may thus limit the accumulation of neurotoxic metabolites and preserve the cellular energy status. The aim of this study in a pneumococcal meningitis model was to investigate the effect of vitamin B6 on hippocampal apoptosis by histomorphology, by transcriptomics and by measurement of cellular nicotine amide adenine dinucleotide content. METHODS AND RESULTS Eleven day old Wistar rats were infected with 1x10(6) cfu/ml of S. pneumoniae and randomized for treatment with vitamin B6 or saline as controls. Vitamin B6 led to a significant (p > 0.02) reduction of hippocampal apoptosis. According to functional annotation based clustering, vitamin B6 led to down-regulation of genes involved in processes of inflammatory response, while genes encoding for processes related to circadian rhythm, neuronal signaling and apoptotic cell death were mostly up-regulated. CONCLUSIONS Our results provide evidence that attenuation of apoptosis by vitamin B6 is multi-factorial including down-modulation of inflammation, up-regulation of the neuroprotective brain-derived neurotrophic factor and prevention of the exhaustion of cellular energy stores. The neuroprotective effect identifies vitamin B6 as a potential target for the development of strategies to attenuate brain injury in bacterial meningitis.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Parasitology
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases

UniBE Contributor:

Zysset-Burri, Denise Corinne; Leib, Stephen and Wittwer, Matthias

Subjects:

600 Technology > 630 Agriculture
500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1471-2334

Publisher:

BioMed Central

Funders:

[4] Swiss National Science Foundation
[UNSPECIFIED] UBS Optimus Foundation

Language:

English

Submitter:

Stephen Leib

Date Deposited:

26 May 2014 09:23

Last Modified:

08 Feb 2017 13:51

Publisher DOI:

10.1186/1471-2334-13-393

PubMed ID:

23977941

BORIS DOI:

10.7892/boris.52654

URI:

https://boris.unibe.ch/id/eprint/52654

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