ABSTRACT
Early cognitive deficits are increasingly recognized in patients with Parkinson's disease (PD), and represent an unmet need for the treatment of PD. These early deficits have been difficult to model in mice, and their mechanisms are poorly understood. α-Synuclein is linked to both familial and sporadic forms of PD, and is believed to accumulate in brains of patients with PD before cell loss. Mice expressing human wild-type α-synuclein under the Thy1 promoter (Thy1-aSyn mice) exhibit broad overexpression of α-synuclein throughout the brain and dynamic alterations in dopamine release several months before striatal dopamine loss. We now show that these mice exhibit deficits in cholinergic systems involved in cognition, and cognitive deficits in domains affected in early PD. Together with an increase in extracellular dopamine and a decrease in cortical acetylcholine at 4-6 months of age, Thy1-aSyn mice made fewer spontaneous alternations in the Y-maze and showed deficits in tests of novel object recognition (NOR), object-place recognition, and operant reversal learning, as compared with age-matched wild-type littermates. These data indicate that cognitive impairments that resemble early PD manifestations are reproduced by α-synuclein overexpression in a murine genetic model of PD. With high power to detect drug effects, these anomalies provide a novel platform for testing improved treatments for these pervasive cognitive deficits.
Subject(s)
Brain/pathology , Cognition Disorders/etiology , Parkinson Disease/complications , alpha-Synuclein/metabolism , Animals , Brain/metabolism , Cognition Disorders/metabolism , Cognition Disorders/pathology , Disease Models, Animal , Humans , Immunohistochemistry , Male , Maze Learning , Mice , Mice, Inbred C57BL , Mice, Inbred DBA , Parkinson Disease/metabolism , Parkinson Disease/pathology , alpha-Synuclein/geneticsABSTRACT
This paper seeks to connect adolescents' communication within on-line weblogs or blogs to developmental processes. A total of 195 English language blogs written by self-identified 14- to 18-year-olds were selected; three entries from each blog were analysed, resulting in a sample of 585 entries. Blogger demographics, self-presentation, and blog entries (format, style, content, and tone) were coded. The blog authors in our sample were overwhelmingly female and lived within the US; the majority were between 15- and 16-years of age. Bloggers utilized usernames and userpictures for self-presentation and in addition to gender, frequently presented information about their age and location. The majority of the entries used text, were narrative and reflective in style, and contained themes related to their authors' peers and everyday life. Emotional tone was present and entries with romantic, identity, and future-related themes often contained emotional tone. Blog authors seemed to be using blogs to create narratives and to reflect about the people and events in their lives. Our results show that adolescent bloggers project off-line themes to their blogs, suggesting that their on-line and off-line contexts are psychologically connected.
