Modelos experimentales de enfermedad de Parkinson

This article reviews the most useful animal models of Parkinson's disease available. Basically they include the model of unilateral nigrostriatal lesion induced by 6-hydroxydopamine (6-OHDA) in rodents and the 1-methy-4-phenyl-1,2,3,6, tetrahydropyridine (MPTP) model of parkinsonism in non-human primates. The major neurochemical and histological alterations found in these two models are also analyzed. Finally, possible applications of these models of parkinsonism are also discussed

Sistema dopaminérgico y muerte neuronal

The mechanism involved in dopaminergic neuronal death remains unknown. Increased oxidative stress, inhibition of mitochondrial respiratory chain and apoptosis have been suggested as possible factors mediating cellular death. This article reviews the most important findings reported in parkinsonian brains related to nigral neuronal death

La visión parkinsoniana de la figura compleja de Rey-Osterrieth

Visuospatial impairment has been frequently reported in Parkinson’s disease (PD). We present the progressive distorsioned performance of the Rey-Osterrieth complex figure in parkinsonian patients at different stages of the disease (PD de novo, PD on long-term treatment, PD with phychosis and PD with dementia

Multiple neuroanatomical tracing in primates

The present report deals with a multiple tract-tracing procedure in non-human primates enabling the simultaneous visualization of retrogradely transported Fluoro-Gold (FG) and cholera toxin B subunit (CTB) in combination with anterogradely transported biotinylated dextran amine (BDA). Two issues have played key roles on the achievement of this reliable procedure: first, the recent development of a commercial antiserum against FG that allows us to convert the original fluorescent signal of this dye in a permanent precipitate via standard peroxidase-anti-peroxidase methods; second, the introduction of the novel peroxidase substrate Vector(R) VIP (V-VIP), resulting in a purple precipitate. The combination of these neuroanatomical tracers in one and the same histological section opens a possibility for the permanent visualization of the convergence of inputs from a particular brain area onto identified, two different subsets of projection cells of another area. Furthermore, this combination of three tracers emerges as a powerful technical tool for obtaining broad amounts of complementary data regarding the monkey brain connectivity, thus significantly reducing the number of animals needed to complete a particular study

Trastornos neuropsiquiátricos en la enfermedad de Parkinson

This paper reviews the main neuropsychiatric disorders associated with Parkinson’s disease (PD) and describes the neuropathological hypothesis proposed to explain these symptoms. Development. This disease is usually associated with neuropsychiatric complications such as depression, anxiety and apathy. Besides, psychiatric symptoms are one of the most common side effects of antiparkinsonian drug-therapy. Conclusions. Depression is the most frequent emotional disorder reported in patients with PD. Up to 20% of parkinsonian patients meet DSM-IV criteria for major depressive episode and another 20% for dysthymia, while the prevalence of depression in normal aged population is about 2-8%. The relationship between PD and depression has not been fully established. Some investigators have suggested that depressive symptoms in PD are causally related to the underlying neuropathological process, affecting predominantly serotoninergic and dopaminergic pathways. Alternatively, depression in PD may represent a normal reaction to the progressive physical impairment induced by the disease. Otherwise, up to 20% of parkinsonian patients present levodopa-induced psychiatric complications. Visual hallucinations are the commonest, but delusions, confusional states, sexual disorders and sleep disorders have also been described. Serotonine and dopamine have been implicated in the neuropathological basis of these disorders

Brain aging and Parkinson's disease: new therapeutic approaches using drugs delivery systems

ABSTRACT The etiology and pathogenesis of Parkinson’s disease (PD) is unknown, aging being the strongest risk factor for brain degeneration. Understanding PD pathogenesis and how aging increases the risk of disease would aid the development of therapies able to slow or prevent the progression of this neurodegenerative disorder. In this review we provide an overview of the most promising therapeutic targets and strategies to delay the loss of dopaminergic neurons observed both in PD and aging. Among them, handling alphasynuclein toxicity, enhancing proteasome and lysosome clearance, ameliorating mitochondrial disruptions and modifying the glial environment are so far the most promising candidates. These new and conventional drugs may present problems related to their labile nature and to the difficulties in reaching the brain. Thus, we highlight the latest types of drug delivery system (DDS)-based strategies for PD treatment, including DDS for local and systemic drug delivery. Finally, the ongoing challenges for the discovery of new targets and the opportunities for DDS-based therapies to improve and efficacious PD therapy will be discussed

Neuroimagen estructural y funcional en las enfermedades priónicas humanas

INTRODUCTION: Prion diseases are neurodegenerative disorders resulting from the accumulation of a misfolded isoform of the cellular prion protein (PrPc). They can occur as acquired, sporadic or hereditary forms. Although prion diseases show a wide range of phenotypic variations, pathological features and clinical evolution, they are all characterised by a common unfavourable course and a fatal outcome. REVIEW SUMMARY: Some variants, such as kuru, have practically disappeared, while others, for example the variant Creutzfeldt-Jakob (vCJD) or those attributable to iatrogenic causes, are still in force and pose a challenge to current medicine. There are no definitive pre-mortem diagnostic tests, except for vCJD, where a tonsil biopsy detects 100% of the cases. For this reason, diagnostic criteria dependent on statistical probability have had to be created. These require complementary examinations, such as an electroencephalogram (EEG) or the detection of 14-3-3 protein in cerebrospinal fluid (CSF). Only the "pulvinar sign" in magnetic resonance imaging (MRI) has been included as a vCJD diagnostic criterion. The present review discusses neuroimaging findings for each type of prion disease in patients with a definitive histopathological diagnosis. CONCLUSIONS: The aim is to define the usefulness of these complementary examinations as a tool for the diagnosis of this family of neurodegenerative diseases

Combining Gene Transfer and Nonhuman Primates to Better Understand and Treat Parkinson’s Disease

Parkinson's disease (PD) is a progressive CNS disorder that is primarily associated with impaired movement. PD develops over decades and is linked to the gradual loss of dopamine delivery to the striatum, via the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). While the administration of L-dopa and deep brain stimulation are potent therapies, their costs, side effects and gradual loss of efficacy underlines the need to develop other approaches. Unfortunately, the lack of pertinent animal models that reproduce DA neuron loss and behavior deficits-in a timeline that mimics PD progression-has hindered the identification of alternative therapies. A complementary approach to transgenic animals is the use of nonhuman primates (NHPs) combined with the overexpression of disease-related genes using viral vectors. This approach may induce phenotypes that are not influenced by developmental compensation mechanisms, and that take into account the personality of animals. In this review article, we discuss the combination of gene transfer and NHPs to develop "genetic" models of PD that are suitable for testing therapeutic approaches

Excess abdominal fat is associated with cutaneous allodynia in individuals with migraine: a prospective cohort study

Objective: To investigate the specific relationship between cutaneous allodynia (CA) and the percentages of body fat (BF) and abdominal fat in migraineurs. Additionally, we compared serum levels of inflammatory biomarkers in patients with and without CA. Background: Excess abdominal fat might facilitate progressive changes in nociceptive thresholds causing central sensitization, clinically reflected as CA, which could drive migraine progression. Methods: This prospective cohort study included 80 patients with migraine (mean age 39 years, 81.2% female) and 39 non-migraine controls. We analysed each participant’s height, body weight, and body mass index (BMI). The amount and distribution of BF was also assessed by air displacement plethysmography (ADP) and ViScan, respectively. We analysed serum levels of markers of inflammation, during interictal periods. Results: We studied 52 patients with episodic migraine (EM) and 28 with chronic migraine (CM). Of the 80 patients, 53 (53.8%) had CA. Migraineurs with CA had a higher proportion of abdominal fat values than patients without CA (p = 0.04). The independent risk factors for CA were the use of migraine prophylaxis (OR 3.26, 95% CI [1.14 to 9.32]; p = 0.03), proportion of abdominal fat (OR 1.13, 95% CI [1.01 to 1.27]; p = 0.04), and presence of sleep disorders (OR 1.13, 95% CI [00.01 to 1.27]; p = 0.04). The concordance correlation coefficient between the ADP and BMI measurements was 0.51 (0.3681 to 0.6247). CA was not correlated with the mean plasma levels of inflammatory biomarkers. Conclusions: There is a relation between excess abdominal fat and CA. Abdominal obesity might contribute to the development of central sensitization in migraineurs, leading to migraine chronification