1: J Neuroinflammation. 2007 Jul 21;4:19.

Urocortin, a CRF-like peptide, restores key indicators of damage in the
substantia nigra in a neuroinflammatory model of Parkinson's disease.

Abuirmeileh A, Harkavyi A, Lever R, Biggs CS, Whitton PS.

Department of Pharmacology, The School of Pharmacy, London, UK.
amjad.abuirmeileh@pharmacy.ac.uk <amjad.abuirmeileh@pharmacy.ac.uk>

We have recently observed that the corticotrophin releasing hormone (CRF) related
peptide urocortin (UCN) reverses key features of nigrostriatal damage in the
hemiparkinsonian 6-hydroxydopamine lesioned rat. Here we have studied whether
similar effects are also evident in the lipopolysaccaride (LPS) neuroinflammatory
paradigm of Parkinson's disease (PD). To do this we have measured restoration of
normal motor behaviour, retention of nigral dopamine (DA) and also tyrosine
hydroxylase (TH) activity. Fourteen days following intranigral injections of LPS
and UCN, rats showed only modest circling after DA receptor stimulation with
apomorphine, in contrast to those given LPS and vehicle where circling was
pronounced. In separate experiments, rats received UCN seven days following LPS,
and here apomorphine challenge caused near identical circling intensity to those
that received LPS and UCN concomitantly. In a similar and consistent manner with
the preservation of motor function, UCN 'protected' the nigra from both DA
depletion and loss of TH activity, indicating preservation of DA cells. The
effects of UCN were antagonised by the non-selective CRF receptor antagonist
alpha-helical CRF and were not replicated by the selective CRF2 ligand UCN III.
This suggests that UCN is acting via CRF1 receptors, which have been shown to be
anti-inflammatory in the periphery. Our data therefore indicate that UCN is
capable of maintaining adequate nigrostriatal function in vivo, via CRF1
receptors following a neuro-inflammatory challenge. This has potential
therapeutic implications in PD.

PMCID: PMC1976313
PMID: 17659087 [PubMed - indexed for MEDLINE]