title: Adhesion molecules as potential targets for neuroprotection in a rodent model of Parkinson's disease.
abstract: Cell adhesion molecules might play an important role in the inflammatory mechanisms associated with neurodegeneration. We have previously observed, in rats, that subcutaneous injection of complete Freund's adjuvant (CFA), a pro-inflammatory agent that induces a peripheral inflammatory stimulus, reduces the nigrostriatal degeneration and microglial activation caused by stereotaxic injection of 6-hydroxydopamine (6-OHDA). Here we further investigated the effects of CFA in 6-OHDA-lesioned rats by evaluating the expression of selected adhesion molecules, both at central and peripheral levels. Male, Sprague-Dawley rats received a subcutaneous injection of CFA followed, 10 days later, by intrastriatal injection of 6-OHDA. Animals were sacrificed at various time points and changes affecting intercellular (ICAM-1), vascular (VCAM-1), platelet endothelial (PECAM-1) and neural (NCAM-1) cell adhesion molecules were analyzed in striatum, ventral midbrain (containing the substantia nigra) and sera. Our results confirmed the protective effect of systemic CFA on 6-OHDA-induced nigrostriatal degeneration. Injection of 6-OHDA increased striatal ICAM-1 and PECAM-1 expression, while opposite changes (decreased expression) were detected in the ventral midbrain, particularly for VCAM-1 and NCAM-1. Pretreatment with CFA counteracted these changes. Nigrostriatal degeneration also affected peripheral immune function, with lesioned animals showing increased sPECAM levels with respect to intact animals. Also in this case, CFA pretreatment blocked the 6-OHDA induced increase of sPECAM. Our findings confirm that a pre-existing, peripheral pro-inflammatory condition reduces the neuroinflammatory response and associated neurodegeneration provoked by centrally-administered 6-OHDA, with a mechanism that seems to involve selected adhesion molecules. The link between peripheral and central immune responses may, therefore, represent a target for new therapeutic strategies aimed at reducing the neuroinflammatory component associated with neurodegeneration.
authors.affiliation: Laboratory of Functional Neurochemistry, Interdepartmental Research Center for Parkinson's Disease, CRIMP, IRCCS National Institute of Neurology C Mondino, Pavia, Italy. marie.armentero@mondino.it
authors.forename: Marie-Therese
authors.initials: MT
authors.lastname: Armentero
authors.forename: Giovanna
authors.initials: G
authors.lastname: Levandis
authors.forename: Eleonora
authors.initials: E
authors.lastname: Bazzini
authors.forename: Silvia
authors.initials: S
authors.lastname: Cerri
authors.forename: Cristina
authors.initials: C
authors.lastname: Ghezzi
authors.forename: Fabio
authors.initials: F
authors.lastname: Blandini
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D005620:Freund's Adjuvant / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008297:Male; D009410:Nerve Degeneration / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000378:metabolism*; D016627:Oxidopamine / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D013565:Sympatholytics / Q000633:toxicity; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D019006:Neural Cell Adhesion Molecules; D018696:Neuroprotective Agents; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D013565:Sympatholytics; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D016627:Oxidopamine; D005620:Freund's Adjuvant