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Tracking Parkinson's : Study Design and Baseline Patient Data

BACKGROUND: There is wide variation in the phenotypic expression of Parkinson's disease (PD), which is driven by both genetic and epidemiological influences.OBJECTIVES: To define and explain variation in the clinical phenotype of PD, in relation to genotypic variation.METHODS: Tracking Parkinson's is a multicentre prospective longitudinal epidemiologic and biomarker study of PD. Patients attending

Rating Apathy in Huntington’s Disease : Patients and Companions Agree

BACKGROUND: Apathy is a common feature of Huntington’s disease (HD), even from early disease. However, patients are believed to lack insight into their own apathy and therefore clinicians and/or companions are relied upon to estimate the extent of a patient’s apathy. In addition, the evolution of apathy over time in HD has not been unequivocally established. OBJECTIVEs: The purpose of this study w

A simple assessment model to quantifying the dynamic hippocampal neurogenic process in the adult mammalian brain

Adult hippocampal neurogenesis is a highly dynamic process in which new cells are born, but only some of which survive. Of late it has become clear that these surviving newborn neurons have functional roles, most notably in certain forms of memory. Conventional methods to look at adult neurogenesis are based on the quantification of the number of newly born neurons using a simple cell counting met

Antidopaminergic Medication is Associated with More Rapidly Progressive Huntington's Disease

BACKGROUND: Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder leading to progressive motor, cognitive and functional decline. Antidopaminergic medications (ADMs) are frequently used to treat chorea and behavioural disturbances in HD.OBJECTIVE: We aimed to assess how the use of such medications was associated with the severity and progression of the motor aspects of the

Gray and white matter imaging : A biomarker for cognitive impairment in early Parkinson's disease?

BACKGROUND: The aim of this work was to investigate the cortical and white matter changes that underlie cognitive impairment in patients with incident Parkinson's disease (PD) disease using voxel-based morphometry and diffusion tensor imaging.METHODS: Newly diagnosed nondemented PD (n = 125) and control subjects (n = 50) were recruited from the Incidence of Cognitive Impairment in Cohorts with Lon

Baseline and longitudinal grey matter changes in newly diagnosed Parkinson's disease : ICICLE-PD study

Mild cognitive impairment in Parkinson's disease is associated with progression to dementia (Parkinson's disease dementia) in a majority of patients. Determining structural imaging biomarkers associated with prodromal Parkinson's disease dementia may allow for the earlier identification of those at risk, and allow for targeted disease modifying therapies. One hundred and five non-demented subjects

Gamma-tubulin coordinates nuclear envelope assembly around chromatin

The cytosolic role of γ-tubulin as a microtubule organizer has been studied thoroughly, but its nuclear function is poorly understood. Here, we show that γ-tubulin is located throughout the chromatin of demembranated Xenopus laevis sperm and, as the nucleus is formed, γ-tubulin recruits lamin B3 and nuclear membranes. Immunodepletion of γ-tubulin impairs X. laevis assembly of both the lamina and t

Beyond prostate-specific antigen : Utilizing novel strategies to screen men for prostate cancer

Purpose of review The purpose of this article is to review blood and urine tests that are currently available and under investigation for a role in prostate cancer screening and detection. Recent findings Compared with total prostate-specific antigen (PSA) alone, its combination with percentage free-to-total PSA contributes greater specificity for prostate cancer, and is a component of two newer b

α-Synuclein induced toxicity in brain stem serotonin neurons mediated by an AAV vector driven by the tryptophan hydroxylase promoter

We studied the impact of α-synuclein overexpression in brainstem serotonin neurons using a novel vector construct where the expression of human wildtype α-synuclein is driven by the tryptophan hydroxylase promoter, allowing expression of α-synuclein at elevated levels, and with high selectivity, in serotonergic neurons. α-Synuclein induced degenerative changes in axons and dendrites, displaying a

Long-term clinical outcome of fetal cell transplantation for Parkinson disease : two case reports

IMPORTANCE: Recent advances in stem cell technologies have rekindled an interest in the use of cell replacement strategies for patients with Parkinson disease. This study reports the very long-term clinical outcomes of fetal cell transplantation in 2 patients with Parkinson disease. Such long-term follow-up data can usefully inform on the potential efficacy of this approach, as well as the design

Involvement of the serotonin system in L-dopa-induced dyskinesias

The ability of L-dopa to relieve the motor impairments in Parkinson's disease patients declines over time, and side-effects, such as dyskinesias, appear--limiting the use of the drug in the advanced stage of the disease. Serotonergic neurons are able to convert L-dopa to dopamine and to store this neurotransmitter in synaptic vesicles. This peculiarity might be very important in the advanced disea

Striatal c-fos Induction by Cocaine or Apomorphine Occurs Preferentially in Output Neurons Projecting to the Substantia Nigra in the Rat

Fluorogold or rhodamine-labelled latex beads were injected in the substantia nigra (SN) or the globus pallidus (GP) in order retrogradely to label striatal output neurons that project to the two target structures. Ten days later, striatal c-fos was induced by systemic administration of cocaine (five normal rats; 25 mg/kg cocaine i.p. 2 h before killing) or apomorphine (five unilaterally dopamine-d

Host Brain Regulation of Fetal Locus Coeruleus Neurons Grafted to the Hippocampus in 6-Hydroxydopamine-Treated Rats. An Intracerebral Microdialysis Study

Release properties of intrahippocampal transplants of noradrenergic neurons were monitored by microdialysis in awake and halothane-anaesthetized rats. Fetal locus coeruleus neurons were implanted as a cell suspension into hippocampi deprived of their innate noradrenalin (NA) innervation by intraventricular 6-hydroxydopamine treatment. Dialysis probes of the loop type were implanted into the dorsal

The Importance of Graft Placement and Task Complexity for Transplant-Induced Recovery of Simple and Complex Sensorimotor Deficits in Dopamine Denervated Rats

The present study examined the role of graft placement and behavioural task complexity in determining the functional efficacy of intrastriatal grafts of dopamine-rich fetal ventral mesencephalon (VM) placed in the dopamine (DA) depleted striatum. The functional effects of two different striatal placements of VM grafts were evaluated using tests of drug-induced motor asymmetry, simple sensorimotor

Hippocampal Noradrenaline and Serotonin Release over 24 Hours as Measured by the Dialysis Technique in Freely Moving Rats : Correlation to Behavioural Activity State, Effect of Handling and Tail-Pinch

Hippocampal extracellular levels of noradrenaline (NA), 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) were monitored with the microdialysis technique in freely moving rats. In one experiment 30 min samples were collected during 24 h of continuous perfusion, and the monoamine output was compared to the behavioural activity state, as arbitrarily classified in three categories:

Degenerative Changes in Forebrain Cholinergic Nuclei Correlate with Cognitive Impairments in Aged Rats

Degenerative changes in the forebrain cholinergic nuclei have been studied morphometrically in behaviourally characterized aged female Sprague-Dawley rats. In all regions analysed (medial septum, diagonal band of Broca, nucleus basalis, and striatum) the acetylcholinesterase-positive neurons were reduced in both size and number in the aged (24-months-old) rats as compared to the young (3-months-ol