Abstract:
:Previous studies with excitotoxically lesioned organotypic hippocampal slice cultures (OHSC) have revealed that the immunosuppressant mycophenolate mofetil (MMF) inhibits microglial activation and suppresses neuronal injury in the dentate gyrus. We here investigate whether MMF also has beneficial effects on axon survival in a long-range projection, the perforant path. Complex OHSC including the entorhinal cortex were obtained from Wistar rats (p8); the plane of section ensuring that perforant path integrity was preserved. These preparations were cultured for 9 days in vitro with or without MMF (100 microg/ml). After fixation, the perforant path was retrogradely labeled by application of the fluorescent dye DiI (1,1'-dioctadecyl-3,3,3',3'-tetramethylindo-carbocyanine) in the hilus of the dentate gyrus, and neuronal perikarya were immunohistochemically stained by the neuron-specific marker NeuN. Analysis of DiI-labeled and NeuN-stained OHSC by confocal laser scanning microscopy revealed double-labeled neurons in the entorhinal cortex, which projected to the dentate gyrus via the perforant path. Quantitative analysis showed that the number of these double-labeled neurons was 19-fold higher in OHSC treated with MMF than in control cultures (P < 0.05). Our findings indicate that MMF treatment improves preservation of the perforant path and encourage further studies on development and regeneration of long-range projections under the influence of immunosuppressants.
journal_name
Hippocampusjournal_title
Hippocampusauthors
Oest TM,Dehghani F,Korf HW,Hailer NPdoi
10.1002/hipo.20182subject
Has Abstractpub_date
2006-01-01 00:00:00pages
437-42issue
5eissn
1050-9631issn
1098-1063journal_volume
16pub_type
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