Enriched environment fails to increase meningitis‐induced neurogenesis and spatial memory in a mouse model of pneumococcal meningitis

Tauber, Simone C.; Bunkowski, Stephanie; Ebert, Sandra; Schulz, Daniela; Kellert, Benedikt; Nau, Roland; Gerber, Joachim

doi:10.1002/jnr.22010

Cited by 11 publications

(9 citation statements)

References 37 publications

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“…In humans and postnatal mice, pneumococcal meningitis often results in neuronal loss with subsequent impaired memory and cognitive function (Grandgirard et al, 2007; Schmidt et al, 2006; Tauber et al, 2009). In contrast, our data suggest that, within the fetal cortex, CW enhances proliferation of neurons leading to an increase in overall number of neurons in the cortical plate.…”

Section: Resultsmentioning

confidence: 99%

Bacterial Peptidoglycan Traverses the Placenta to Induce Fetal Neuroproliferation and Aberrant Postnatal Behavior

Humann

Mann

Gao

et al. 2016

Cell Host & Microbe

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Summary Maternal infection during pregnancy is associated with adverse outcomes for the fetus, including postnatal cognitive disorders. However, the underlying mechanisms are obscure. We find that bacterial cell wall peptidoglycan (CW), a universal PAMP for TLR2, traverses across the murine placenta into the developing fetal brain. In contrast to adults, CW-exposed fetal brains did not show any signs of inflammation or neuronal death. Instead, the neuronal transcription factor FoxG1 was induced and neuroproliferation leading to a 50% greater density of neurons in the cortical plate was observed. Bacterial infection of pregnant dams followed by antibiotic treatment, which releases CW, yielded the same result. Neuroproliferation required TLR2 and was recapitulated in vitro with fetal neuronal precursor cells and TLR2/6, but not TLR2/1 ligands. The fetal neuroproliferative response correlated with abnormal cognitive behavior in CW-exposed pups following birth. Thus, the bacterial CW-TLR2 signaling axis affects fetal neurodevelopment and may underlie postnatal cognitive disorders.

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Section: Resultsmentioning

confidence: 99%

Bacterial Peptidoglycan Traverses the Placenta to Induce Fetal Neuroproliferation and Aberrant Postnatal Behavior

Humann

Mann

Gao

et al. 2016

Cell Host & Microbe

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“…Indeed, only two studies have investigated the effect of an EE on brain infections using experimental models [35], [36], but their approach to quantifying neuropathological changes was not based on unbiased stereological estimations. As a result, quantitative associations between neuropathological features and behavioral changes in murine models of encephalitis and the effect of EE have previously not been firmly established.…”

Section: Discussionmentioning

confidence: 99%

Influence of Enriched Environment on Viral Encephalitis Outcomes: Behavioral and Neuropathological Changes in Albino Swiss Mice

et al. 2011

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An enriched environment has previously been described as enhancing natural killer cell activity of recognizing and killing virally infected cells. However, the effects of environmental enrichment on behavioral changes in relation to virus clearance and the neuropathology of encephalitis have not been studied in detail. We tested the hypothesis that environmental enrichment leads to less CNS neuroinvasion and/or more rapid viral clearance in association with T cells without neuronal damage. Stereology-based estimates of activated microglia perineuronal nets and neurons in CA3 were correlated with behavioral changes in the Piry rhabdovirus model of encephalitis in the albino Swiss mouse. Two-month-old female mice maintained in impoverished (IE) or enriched environments (EE) for 3 months were behaviorally tested. After the tests, an equal volume of Piry virus (IEPy, EEPy)-infected or normal brain homogenates were nasally instilled. Eight days post-instillation (dpi), when behavioral changes became apparent, brains were fixed and processed to detect viral antigens, activated microglia, perineuronal nets, and T lymphocytes by immuno- or histochemical reactions. At 20 or 40 dpi, the remaining animals were behaviorally tested and processed for the same markers. In IEPy mice, burrowing activity decreased and recovered earlier (8–10 dpi) than open field (20–40 dpi) but remained unaltered in the EEPy group. EEPy mice presented higher T-cell infiltration, less CNS cell infection by the virus and/or faster virus clearance, less microgliosis, and less damage to the extracellular matrix than IEPy. In both EEPy and IEPy animals, CA3 neuronal number remained unaltered. The results suggest that an enriched environment promotes a more effective immune response to clear CNS virus and not at the cost of CNS damage.

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“…Once mice located the platform, they were permitted to remain on it for 10 sec. If mice did not locate the platform within 90 sec, they were placed on the platform for 10 sec and then removed from the pool, as previously described (14,15).…”

Section: Volume Measurement Of the Granular Cell Layer Of The Dgmentioning

confidence: 99%

Forced mastication increases survival of adult neural stem cells in the hippocampal dentate gyrus

Akazawa

Kitamura

Fujihara

et al. 2012

International Journal of Molecular Medicine

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Abstract. In this study, we examined the effect of forced mastication on neurogenesis in the hippocampal dentate gyrus (DG) of adult mice. Six-week-old mice were subjected to either a hard or normal diet for 13 weeks. They received a daily injection of bromodeoxyuridine (BrdU) for 12 consecutive days beginning at 14 weeks of age. The number of BrdU-positive cells in the DG was counted 1 day after and 5 weeks after the final BrdU injection. The number of BrdU-positive cells 1 day after injection did not differ between the 2 diet groups. However, the number of BrdU-positive cells in the group fed the hard diet was significantly increased 5 weeks after BrdU injection compared to the group fed the normal diet. The results of the Morris water maze test showed that mice fed a hard diet required significantly less time to reach the platform than the control mice when tested at 10 days. Moreover, mice in the group fed the hard diet spent significantly more time in the former platform area than the group fed the normal diet, indicating that hard diet feeding improved spatial memory compared to normal diet feeding. Real-time PCR analysis showed that the expression of glutamate receptor 1 mRNA was significantly increased in the group fed the hard diet compared with the group fed the normal diet. These results suggest that mastication increases the survival of adult neural stem cells in the hippocampal DG.

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Enriched environment fails to increase meningitis‐induced neurogenesis and spatial memory in a mouse model of pneumococcal meningitis

Cited by 11 publications

References 37 publications

Bacterial Peptidoglycan Traverses the Placenta to Induce Fetal Neuroproliferation and Aberrant Postnatal Behavior

Bacterial Peptidoglycan Traverses the Placenta to Induce Fetal Neuroproliferation and Aberrant Postnatal Behavior

Influence of Enriched Environment on Viral Encephalitis Outcomes: Behavioral and Neuropathological Changes in Albino Swiss Mice

Forced mastication increases survival of adult neural stem cells in the hippocampal dentate gyrus

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