Garikoitz Azkona

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OBJECTIVES The aim of this study was to describe the prevalence and severity of behavioural changes associated with age and their relationship to risk factors such as sex, reproductive status, bodyweight and age. METHODS A cross-sectional study design was chosen. A total of 325 geriatric dogs were included. Owners of dogs older than nine years were(More)
L-DOPA is the most effective treatment for Parkinson's disease (PD), but prolonged use leads to disabling motor complications including dyskinesia. Strong evidence supports a role of the subthalamic nucleus (STN) in the pathophysiology of PD whereas its role in dyskinesia is a matter of controversy. Here, we investigated the involvement of STN in(More)
Dopamine replacement with l-DOPA is the most effective therapy in Parkinson's disease. However, with chronic treatment, half of the patients develop an abnormal motor response including dyskinesias. The specific molecular mechanisms underlying dyskinesias are not fully understood. In this study, we used a well-characterized animal model to first establish(More)
BACE2 is homologous to BACE1, a beta-secretase that is involved in the amyloidogenic pathway of amyloid precursor protein (APP), and maps to the Down syndrome critical region of chromosome 21. Alzheimer disease neuropathology is common in Down syndrome patients at relatively early ages, and it has thus been speculated that BACE2 co-overexpression with APP(More)
Down syndrome (DS) associates with impaired brain functions, but the underlying mechanism(s) are yet unclear. The "gene dosage" hypothesis predicts that in DS, overexpression of a single gene can impair multiple brain functions through a signal amplification effect due to impaired regulatory mechanism(s). Here, we report findings attributing to impairments(More)
Down syndrome, the most common genetic disorder leading to mental retardation, is caused by the presence of all or part of an extra copy of chromosome 21. At relatively early ages, Down syndrome patients develop progressive formation and extracellular aggregation of amyloid-β peptide, considered as one of the causal factors for the pathogenesis of(More)
Brain-derived neurotrophic factor (BDNF) regulates synaptic strengthening and memory consolidation, and altered BDNF expression is implicated in a number of neuropsychiatric and neurodegenerative disorders. BDNF potentiates N-methyl-D-aspartate receptor function through activation of Fyn and ERK1/2. STriatal-Enriched protein tyrosine Phosphatase (STEP) is(More)
Mutations in PINK1 (PARK6), a serine/threonine kinase involved in mitochondrial homeostasis, are associated with early onset Parkinson’s disease. Fibroblasts from Parkinson’s disease patients with compound heterozygous mutations in exon 7 (c.1488 + 1G > A; c.1252_1488del) showed no apparent signs of mitochondrial impairment. To elucidate changes primarily(More)
Levodopa-induced dyskinesias (LID) are a frequent complication of Parkinson’s disease pharmacotherapy that causes significant disability and narrows the therapeutic window. Pharmacological management of LID is challenging partly because the precise molecular mechanisms are not completely understood. Here, our aim was to determine molecular changes that(More)
Brain mitochondrial complex I (CI) damage is associated with the loss of the dopaminergic neurons of the Substantia Nigra in Parkinson's Disease (PD) patients. However, whether CI inhibition is associated with any alteration of the mitochondrial respiratory chain (MRC) organization in PD patients is unknown. To address this issue, here we analyzed the MRC(More)