ABSTRACT
Prion diseases are fatal neurodegenerative disorders with sporadic, genetic or acquired etiologies. The molecular alterations leading to the onset and the spreading of these diseases are still unknown. In a previous work we identified a five-gene signature able to distinguish intracranially BSE-infected macaques from healthy ones, with SERPINA3 showing the most prominent dysregulation. We analyzed 128 suitable frontal cortex samples, from prion-affected patients (variant Creutzfeldt-Jakob disease (vCJD) n = 20, iatrogenic CJD (iCJD) n = 11, sporadic CJD (sCJD) n = 23, familial CJD (gCJD) n = 17, fatal familial insomnia (FFI) n = 9, Gerstmann-Sträussler-Scheinker syndrome (GSS)) n = 4), patients with Alzheimer disease (AD, n = 14) and age-matched controls (n = 30). Real Time-quantitative PCR was performed for SERPINA3 transcript, and ACTB, RPL19, GAPDH and B2M were used as reference genes. We report SERPINA3 to be strongly up-regulated in the brain of all human prion diseases, with only a mild up-regulation in AD. We show that this striking up-regulation, both at the mRNA and at the protein level, is present in all types of human prion diseases analyzed, although to a different extent for each specific disorder. Our data suggest that SERPINA3 may be involved in the pathogenesis and the progression of prion diseases, representing a valid tool for distinguishing different forms of these disorders in humans.
Subject(s)
Frontal Lobe/metabolism , Prion Diseases/genetics , Prions/genetics , Serpins/genetics , Adult , Aged , Alzheimer Disease/genetics , Alzheimer Disease/physiopathology , Animals , Creutzfeldt-Jakob Syndrome/genetics , Creutzfeldt-Jakob Syndrome/physiopathology , Female , Frontal Lobe/physiopathology , Gene Expression Regulation/genetics , Gerstmann-Straussler-Scheinker Disease/genetics , Gerstmann-Straussler-Scheinker Disease/physiopathology , Humans , Insomnia, Fatal Familial/genetics , Insomnia, Fatal Familial/physiopathology , Male , Middle Aged , Prion Diseases/classification , Prion Diseases/physiopathology , Ribosomal Proteins/geneticsABSTRACT
The present study was undertaken to clarify further whether the programming of direction and extent of the same motor trajectory is accomplished by parallel or serial processing channels. We reasoned that if direction and distance are independently specified, then the time course of each process should not be influenced by the need for simultaneously specifying the other parameter. If direction and distance are specified in a serial order, the need to specify two parameters rather than only one should prolong the process of response specification. For this purpose experiments were run on the same six subjects, using our time-response paradigm and the data obtained were compared. To avoid any possible effect attributable to the Hick and Hyman law, the number of targets was maintained invariant and equal to four. Our major finding is that the time course of directional specification of reaching movements is not influenced by the need for simultaneously specifying extent. This is consistent with our view of parameterization of planning and executing movements, in which the two parameters (direction, extent) can be specified in parallel.
