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Background: Recombinant adeno-associated viruses (rAAV) are a widely used type of
viral transduction vectors. Although the efficiency of this transduction method has
been extensively studied in the (central) nervous system, little is known about the
targeting of the enteric nervous system (ENS) by rAAV. Our aim was hence to assess
the transduction in the ENS by rAAV2/8 and rAAV2/9. Methods: Mice were injected i.v.
with rAAV at postnatal day 1. The rAAV vectors encoded the transgene for enhanced
green fluorescent protein (eGFP) under the control of a CMV promoter. Using immunohistochemical
staining for neurochemical subclasses of enteric neurons in whole mount preparations
of colon and ileum, eGFP expression in the ENS was evaluated at postnatal day 35.
Results: Both rAAV2/8 and rAAV2/9 transduction resulted in eGFP expression in a quarter
of the myenteric and ileal submucous neurons, whereas eGFP expression was remarkably
lower in the submucous plexus of the colon. eGFP-labeled enteric neurons could be
labeled with VIP, calretinin, calbindin or neuronal NOS, indicating that all functional
enteric neuronal subtypes are susceptible to rAAV transduction. Staining with S100
or GFAP did not reveal any significant transduction of enteric glia. Conclusion: Our
results on rAAV-transduction of myenteric neurons corroborate the recent findings
of Gombash et al. (Front Mol Neurosci 2014) and expand the application of rAAV transduction
to the submucous plexus. This approach allows manipulation of specific neuronal subpopulations
in vivo, which is a useful research tool in the short term and a possible therapeutic
strategy in the longer term. This study is funded by grant G019314N of the Research
Foundation – Flanders (FWO).
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