Short report

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

Amjad Abuirmeileh¹ , Alexander Harkavyi¹ , Rebecca Lever¹ , Christopher S Biggs² and Peter S Whitton¹

¹Department of Pharmacology, The School of Pharmacy, 29–39 Brunswick Square, London WC1N 1AX, UK

²School of Biosciences, University of Westminster, 115 New Cavendish Street, London W1W 6UW, UK

author email corresponding author email

Journal of Neuroinflammation 2007, 4:19doi:10.1186/1742-2094-4-19

Published:	21 July 2007

Abstract

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 α-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.