title: Assessment of calcium-binding proteins (Parvalbumin and Calbindin D-28K) and perineuronal nets in normal and scrapie-affected adult sheep brains.
abstract: Scrapie is a prion disease in small ruminants that manifests itself with neurological clinical signs amongst which are ataxia and tremors. These signs can be explained partially by an imbalance in central inhibitory innervation. The study of the brain's inhibitory neuronal GABAergic populations and of their extracellular matrix has been used to define, in part, the pathogenesis of human prion diseases and scrapie models in rodents. The brain's distribution of neuronal GABAergic subpopulations has been monitored carefully using, as markers, antibodies against the calcium binding proteins parvalbumin and calbindin D-28K. The distribution of this perineuronal net marker was evaluated by means of affinity histochemistry with W. floribunda agglutinin. These techniques were performed on the brains of nine scrapie-positive sheep and on four infection-free sheep. These animals had undergone previously a clinical follow-up as well as a lesion profile and an immunohistochemical profile of the scrapie-associated prion protein deposition in the brain. The study of calcium-binding proteins revealed an alteration of the parvalbumin positive GABAergic neuronal subpopulation. In scrapie-positive cases, a reduction in stained neuronal perykaria was observed, along with a marked reduction of neurite labelling. This finding was noticeable in regions such as the neocortex, particularly the motor frontal cortex, and was concomitant with a moderate PrPsc deposition and a mild degree of lesion. No changes were observed in the extracellular matrix study. The results of the present study provide a partial explanation for the mechanisms of scrapie clinical signs due to a disturbance of the parvalbumin-positive inhibitory neuronal population.
authors.affiliation: PRIOCAT Laboratory, CReSA, Veterinary Faculty, Universitat Autònoma de Barcelona, 08193 Bellaterra (Cerdanyola del Vallès), Barcelona, Spain.
authors.forename: Enric
authors.initials: E
authors.lastname: Vidal
authors.forename: Rosa
authors.initials: R
authors.lastname: Bolea
authors.forename: Raül
authors.initials: R
authors.lastname: Tortosa
authors.forename: Carme
authors.initials: C
authors.lastname: Costa
authors.forename: Anna
authors.initials: A
authors.lastname: Domènech
authors.forename: Eva
authors.initials: E
authors.lastname: Monleón
authors.forename: Antonia
authors.initials: A
authors.lastname: Vargas
authors.forename: Juan Jose
authors.initials: JJ
authors.lastname: Badiola
authors.forename: Martí
authors.initials: M
authors.lastname: Pumarola
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D064026:Calbindins; D003593:Cytoplasm / Q000737:chemistry / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D007150:Immunohistochemistry; D008853:Microscopy; D019579:Neocortex / Q000378:metabolism / Q000473:pathology; D016501:Neurites / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D010320:Parvalbumins / Q000378:metabolism*; D018620:PrPSc Proteins / Q000378:metabolism; D064030:S100 Calcium Binding Protein G / Q000378:metabolism*; D012608:Scrapie / Q000378:metabolism / Q000473:pathology*; D012756:Sheep
chemical_list: D064026:Calbindins; D010320:Parvalbumins; D018620:PrPSc Proteins; D064030:S100 Calcium Binding Protein G