Analysis of Neurogenesis during Experimental Autoimmune Encephalomyelitis Reveals Pitfalls of Bioluminescence Imaging

PLoS ONE, 2015 · DOI: 10.1371/journal.pone.0118550 · Published: March 17, 2015

Simple Explanation

This study investigates neurogenesis, the generation of new neurons, during autoimmune brain inflammation using a technique called bioluminescence imaging (BLI). The researchers used transgenic mice that express luciferase, a light-emitting enzyme, under the control of a marker for neuronal progenitor cells (NPCs). They found that while BLI initially showed an increase in neurogenesis during experimental autoimmune encephalomyelitis (EAE), further analysis revealed this was likely due to a leaky blood-brain barrier, rather than actual changes in neurogenesis.

Study Duration

28 days

Participants

DCX-luc reporter mice

Evidence Level

Not specified

Key Findings

1
In vivo bioluminescence imaging showed a marked increase in signal intensity after EAE induction, suggesting increased neurogenesis.
2
Immunostaining for DCX, a marker for neuronal progenitor cells, did not reveal any significant differences between EAE and control mice.
3
The increase in bioluminescence signal was not specific to EAE, as incomplete immunization also resulted in a similar increase, suggesting a disruption of the blood-brain barrier.

Research Summary

The study aimed to investigate changes in adult neurogenesis during EAE using bioluminescence imaging (BLI) in DCX-luc mice and validate findings with immunohistochemistry. In vivo BLI showed an early increase in bioluminescence signal intensity in EAE mice, but immunostaining did not confirm increased DCX expression. The study concludes that the early effects of acute autoimmune CNS inflammation on adult neurogenesis are not perspicuous, and BBB integrity must be considered when using luciferase reporter strains.

Practical Implications

Interpreting BLI results

When using BLI to study neurogenesis or other CNS processes during inflammation, researchers need to be cautious about interpreting changes in bioluminescence signal as direct measures of cellular activity.

BBB integrity

The integrity of the blood-brain barrier (BBB) can significantly influence the availability of luciferase substrates and thus affect the bioluminescence signal, potentially leading to misleading conclusions.

Alternative methods

Combining BLI with other techniques, such as immunohistochemistry and ex vivo luciferase assays, is crucial for validating findings and distinguishing between changes in gene expression and changes in BBB permeability.

Study Limitations

1
The early effects of acute autoimmune CNS inflammation on adult neurogenesis are not perspicuous.
2
Two and four weeks after immunization with CFA+PTX+MOG, we did not detect significant differences in the number of DCX-expressing NPCs within neurogenic regions.
3
the effects of immunization or treatments on the BBB in-tegrity must be taken into account.

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