Current Parkinson's disease research focusses on investigating treatment strategies that are able to slow down the dopaminergic neuronal cell death. The 6-hydroxydopamine (6-OHDA) rat model is ideal for studying the possible neuroprotective effects of certain drugs since different degrees of denervation can be established. Injection of 6-OHDA in the medial forebrain bundle (MFB) results in a complete lesion (_90%), whereas administration of this neurotoxin in the striatum creates only a partial lesion (±50%). Although differences can be detected more easily in the MFB lesion model, the neuroprotective action of certain drugs requires the presence of remaining dopaminergic neurons. Therefore it is useful to screen potential neuroprotective drugs in both models. In these models we have adapted our methodological approach to obtain maximal data from one animal. After determining motor behavior using the cylinder test followed by amphetamine-induced rotation (Rotameter), we sacrifice the rat, take out the striatum and post-fixate the caudal part of the brain for tyrosine hydroxylase immunostaining. The use of a sucrose-solution with protease inhibitor for homogenization of the striatum allows us to determine the dopamine content with HPLC as well as the protein content (GDNF, GAP43,...) in the same sample. Different techniques (Western blotting, ELISA,...) can be applied, depending on the characteristics of the protein. Using this approach we are currently investigating the neuroprotective effects of different ligands of the renin-angiontensin system. In a first series of experiments, intact and MFB lesioned rats were treated subcutaneously with different doses of candesartan, a highly potent and selective AT(1) receptor antagonist, during various time periods.
Original languageEnglish
Title of host publicationPENS Summer School
Publication statusPublished - 2007
EventFinds and Results from the Swedish Cyprus Expedition: A Gender Perspective at the Medelhavsmuseet - Stockholm, Sweden
Duration: 21 Sep 200925 Sep 2009

Publication series

NamePENS Summer School

Conference

ConferenceFinds and Results from the Swedish Cyprus Expedition: A Gender Perspective at the Medelhavsmuseet
CountrySweden
CityStockholm
Period21/09/0925/09/09

    Research areas

  • Parkinson's disease, neuroprotection, 6-hydroxydopamine

ID: 1751922