ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2006) 12 P73

Adrenomedullin in a rat model of multiple sclerosis

S Barker1, R Mongru1, C Bolton2 & C Paul3

1Queen Mary, University of London, London, United Kingdom; 2William Harvey Research Institute, London, United Kingdom; 3University of West England, London, United Kingdom.

The vasoactive peptide adrenomedullin (ADM) has effects on several vascular beds including the cerebral circulation. The peptide has a positive impact on blood-brain-barrier (BBB) integrity, and transcription of ADM mRNA is enhanced by pro-inflammatory cytokines, IL-1 and TNF-alpha in neuronal cell types. The current study has investigated whether ADM may be a marker for disease progression, in vivo in experimental allergic encephalomyelitis (EAE), a model of the human disease multiple sclerosis (MS). EAE is characterised by a loss of BBB integrity and locally high levels of pro-inflammatory cytokines derived from infiltrating T-lymphocytes and macrophages. Animals were un-anaesthetised and sacrificed at the end of the experimental period for dissection of tissues. Total RNA was extracted from medulla-pons, cerebellum and cervical spinal cord tissues from normal and EAE-inoculated Lewis rats. ADM mRNA levels were determined, using RT-PCR, for disease-free, peak of disease and full recovery from neurological symptoms of EAE.

ADM mRNA was increased 50% above control levels in medulla-pons and cerebellum at the peak of disease but returned to control levels after recovery from neurological EAE. In contrast, the levels of ADM mRNA in cervical spinal cord were only elevated after recovery.

The changes in ADM expression during expression during EAE tentatively suggests the peptide may have a role in MS. ADM has positive effects in some tissues towards the expression of anti-inflammatory cytokines, for example IL-10. However, whether ADM is a disease marker or a mediator of recovery remains to be determined.

Table 1 ADM mRNA changes during EAE in Lewis rats
TissueControlPeak diseaseAfter recovery
Medulla pons100±12.6144*±9.0109±9.6
Values are % basal ±S.E.M. *P=<0.05; **P=0.01; CSC=cervical spinal cord

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