Novel Variants in and Identified in Latino Parkinson Disease Cohort Enriched for Caribbean Origin.

The Latino population is greatly understudied in biomedical research, including genetics. Very little information is available on presence of known variants originally identified in non-Hispanic white patients or novel variants in the Latino population. The Latino population is admixed, with contributions of European, African, and Amerindian ancestries.

Stimulus Sensitive Foot Myoclonus: A Clue to Coeliac Disease.

Background: Coeliac disease (CD) is an autoimmune enteropathy that may feature extraintestinal manifestations including cerebellar ataxia and myoclonus.

Methods And Results: A descriptive series of five patients with CD who presented with prominent stimulus-sensitive foot myoclonus.

Conclusions: Stimulus-sensitive foot myoclonus is a distinct clinical sign and may be a useful clue to the diagnosis of CD.

Parkinsonian monkeys with prior levodopa-induced dyskinesias followed by fetal dopamine precursor grafts do not display graft-induced dyskinesias.

Clinical trials testing the hypothesis that fetal dopamine grafts would provide antiparkinsonian benefit in patients who had already developed side effects from their long-term use of L-dopa revealed, in some cases, the presence of dyskinesias even in the absence of L-dopa. The form, intensity, and frequency of these dyskinesias were quite variable, but their manifestation slowed the clinical development of cell replacement therapies. Rodent models of graft-induced dyskinesias (GIDs) have been proposed, but their accuracy in modeling GIDs has been questioned because they usually require amphetamine for their presentation.

Reversibility of tardive dyskinesia syndrome.

In Response To: Zutshi D, Cloud LJ, Factor SA. Dopamine receptor blocking agents: Experience from a university-based movement disorder clinic. Tremor Other Hyperkinet Mov.

An unusual cause of muscle weakness: a diagnostic challenge.

We report a case of 24 year-old-female presenting with bilateral leg heaviness sensation and difficult walking of one-day duration. Over the past three months she developed progressive and frequent tingling sensation on her hands accompanied by headache and increased thirst. Hypokalemia was identified and treated with resolution of symptoms.

Fate mapping and lineage analyses demonstrate the production of a large number of striatal neuroblasts after transforming growth factor alpha and noggin striatal infusions into the dopamine-depleted striatum.

Infusion of transforming growth factor alpha (TGFalpha) into the adult dopamine (DA)-depleted striatum generates a local population of nestin(+)/proliferating cell nuclear antigen (PCNA)(+) newborn cells. The precise origin and fate of these new striatal cells are unknown, making it difficult to direct them for neural repair in Parkinson's disease. Experiments in rats using 5-bromo-2'-deoxyuridine (BrdU) to label neural progenitor cells showed that during TGFalpha infusion in the DA-depleted striatum, newborn striatal cells formed a homogeneous population of precursors, with the majority coexpressing nestin, Mash1, Olig2, and epidermal growth factor receptor, consistent with the phenotype of multipotent C cells.

Dopamine neurons implanted into people with Parkinson's disease survive without pathology for 14 years.

Postmortem analysis of five subjects with Parkinson's disease 9-14 years after transplantation of fetal midbrain cell suspensions revealed surviving grafts that included dopamine and serotonin neurons without pathology. These findings are important for the understanding of the etiopathogenesis of midbrain dopamine neuron degeneration and future use of cell replacement therapies.

Embryonic stem cell-derived Pitx3-enhanced green fluorescent protein midbrain dopamine neurons survive enrichment by fluorescence-activated cell sorting and function in an animal model of Parkinson's disease.

Both fetal ventral mesencephalic (VM) and embryonic stem (ES) cell-derived dopamine neurons have been used successfully to correct behavioral responses in animal models of Parkinson's disease. However, grafts derived from fetal VM cells or from ES cells contain multiple cell types, and the majority of these cells are not dopamine neurons. Isolation of ES cell-derived dopamine neurons and subsequent transplantation would both elucidate the capacity of these neurons to provide functional input and also further explore an efficient and safer use of ES cells for the treatment of Parkinson's disease.

Recent advances in cell-based therapy for Parkinson disease.

In this review, the authors discuss recent advances in the field of cell therapy for Parkinson disease (PD). They compare and contrast recent clinical trials using fetal dopaminergic neurons. They attribute differences in cell preparation techniques, cell type specification, and immunosuppression as reasons for variable outcome and for some of the side effects observed in these clinical trials.

Inhibition of the dopamine D1 receptor signaling by PSD-95.

Dopamine D1 receptors play an important role in movement, reward, and learning and are implicated in a number of neurological and psychiatric disorders. These receptors are concentrated in dendritic spines of neurons, including the spine head and the postsynaptic density. D1 within spines is thought to modulate the local channels and receptors to control the excitability and synaptic properties of spines.

Selection of embryonic stem cell-derived enhanced green fluorescent protein-positive dopamine neurons using the tyrosine hydroxylase promoter is confounded by reporter gene expression in immature cell populations.

Transplantation of mouse embryonic stem (mES) cells can restore function in Parkinson disease models, but can generate teratomas. Purification of dopamine neurons derived from embryonic stem cells by fluorescence-activated cell sorting (FACS) could provide a functional cell population for transplantation while eliminating the risk of teratoma formation. Here we used the tyrosine hydroxylase (TH) promoter to drive enhanced green fluorescent protein (eGFP) expression in mES cells.

RC3/neurogranin is expressed in pyramidal neurons of motor and somatosensory cortex in normal and denervated monkeys.

RC3/neurogranin is a neuron-specific calpacitin located in the cytoplasm and, especially, in dendrites and dendritic spines of cortical neurons, involved in many aspects of excitatory transmission and long-term potentiation. We investigated RC3 expression in pyramidal cortical neurons and interneurons of the motor and somatosensory cortex of normal Macaca fascicularis by means of double immunofluorescence and with techniques that combine immunohistochemistry and radioactive in situ hybridization. We show that RC3 is expressed in virtually all pyramidal neurons and spiny stellate neurons of neocortical areas 4, 3b, 1, 2, 5, 7, and SII, but not in the majority of cortical interneurons.

Long-term survival of dopamine neurons derived from parthenogenetic primate embryonic stem cells (cyno-1) after transplantation.

Dopamine (DA) neurons can be derived from human and primate embryonic stem (ES) cells in vitro. An ES cell-based replacement therapy for patients with Parkinson's disease requires that in vitro-generated neurons maintain their phenotype in vivo. Other critical issues relate to their proliferative capacity and risk of tumor formation, and the capability of migration and integration in the adult mammalian brain.

Cell type analysis of functional fetal dopamine cell suspension transplants in the striatum and substantia nigra of patients with Parkinson's disease.

We report the first post-mortem analysis of two patients with Parkinson's disease who received fetal midbrain transplants as a cell suspension in the striatum, and in one case also in the substantia nigra. These patients had a favourable clinical evolution and positive 18F-fluorodopa PET scans and did not develop motor complications. The surviving transplanted dopamine neurons were positively identified with phenotypic markers of normal control human substantia nigra (n = 3), such as tyrosine hydroxylase, G-protein-coupled inward rectifying current potassium channel type 2 (Girk2) and calbindin.