Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Description of the phenomenology of movement disorders requires precise and accurate terminology. Many of the terms that have been widely used in the literature are imprecise and open to interpretation. An examination of these terms and the assumptions implicit in their usage is important to improve communication and hence the definition, diagnosis, and treatment of movement disorders. I recommend that the term dyskinesia should be used primarily in the settings of Parkinson's disease and tardive dyskinesia, in which its clinical implications are relatively clear; it should not be used in other situations where a precise description could more usefully facilitate diagnosis and treatment. In general dyskinesia should be used in the singular form. Extrapyramidal is based upon obsolete anatomical concepts, is uninformative, and should be discarded. The term abnormal involuntary movements (AIMs) is similarly vague and uninformative, although is unlikely to be eliminated from the psychiatric literature. Movement disorder neurologists as teachers, clinicians, article reviewers, and journal editors have the responsibility to educate our colleagues regarding appropriate usage and the importance of employing correct descriptors.
Tremor Other Hyperkinet Mov (N Y) 2013
PMID:Thoughts on selected movement disorder terminology and a plea for clarity. 2439 9

Parkinson's disease is a progressive neurodegenerative disorder associated with tremor, rigidity, and bradykinesia, as well as nonmotor symptoms including autonomic impairments, olfactory dysfunction, sleep disturbances, depression, and dementia. Although the major neurological deficit is a loss of nigrostriatal dopaminergic neurons, multiple neurotransmitters systems are compromised in Parkinson's disease. Consistent with this observation, dopamine replacement therapy dramatically improves Parkinson's disease motor symptoms. Additionally, drugs targeting the serotonergic, glutamatergic, adenosine, and other neurotransmitter systems may be beneficial. Recent evidence also indicates that nicotinic cholinergic drugs may be useful for the management of Parkinson's disease. This possibility initially arose from the results of epidemiological studies, which showed that smoking was associated with a decreased incidence of Parkinson's disease, an effect mediated in part by the nicotine in smoke. Further evidence for this idea stemmed from preclinical studies which showed that nicotine administration reduced nigrostriatal damage in parkinsonian rodents and monkeys. In addition to a potential neuroprotective role, emerging work indicates that nicotinic receptor drugs improve the abnormal involuntary movements or dyskinesias that arise as a side effect of l-dopa treatment, the gold standard therapy for Parkinson's disease. Both nicotine and nicotinic receptor drugs reduced l-dopa-induced dyskinesias by over 50% in parkinsonian rodent and monkey models. Notably, nicotine also attenuated the abnormal involuntary movements or tardive dyskinesias that arise with antipsychotic treatment. These observations, coupled with reports that nicotinic receptor drugs have procognitive and antidepressant effects, suggest that central nervous system (CNS) nicotinic receptors may represent useful targets for the treatment of movement disorders.
...
PMID:Nicotine and Nicotinic Receptor Drugs: Potential for Parkinson's Disease and Drug-Induced Movement Disorders. 2647 32

Parkinson's disease (PD) is characterized by the degeneration of dopaminergic neurons in the substantia nigra, the depletion of striatal dopamine and the presence of Lewy aggregates containing alpha-synuclein. Clinically, there are motor impairments involving cardinal movement symptoms, bradykinesia, resting tremor, muscle rigidity, and postural abnormalities, along with non-motor symptoms such as sleep, behavior and mood disorders. The current treatment for PD focuses on restoring dopaminergic neurotransmission by l-3,4-dihydroxyphenylalanine (levodopa), which loses therapeutic efficacy and induces disabling abnormal involuntary movements known as levodopa-induced dyskinesia (LID) after several years. Evidence indicates that the pathophysiology of both PD and LID disorders is also associated with the dysfunctional activity of the serotonergic (5-HT) neurons that may be responsible for motor and non-motor disturbances. The main population of 5-HT neurons is located in the dorsal raphe nuclei (DRN), which provides extensive innervation to almost the entire neuroaxis and controls multiple functions in the brain. The degeneration of DRN 5-HT neurons occurs in early PD. These neurons can also take exogenous levodopa to transform it into dopamine, which may disturb neuron activity. This review will provide an overview of the underlying mechanisms responsible for 5-HT dysfunction and its clinical relevance in PD and dyskinesia.
 ...
PMID:Dysfunction of serotonergic neurons in Parkinson's disease and dyskinesia. 3134 30

Parkinson's disease (PD) is characterized by progressive loss of midbrain dopaminergic neurons and treated with the dopamine precursor, 3,4-dihydroxy-l-phenylalanine (L-DOPA). Prolonged L-DOPA treatment is however associated with waning efficacy and the induction of L-DOPA induced dyskinesia (LID). GPR88 is an orphan G-protein Coupled Receptor (GPCR) expressed in dopaminoceptive striatal medium spiny neurons (MSNs) and their afferent corticostriatal glutamatergic neurons. Here, we studied the role of GPR88 in experimental parkinsonism and LID. Chronic L-DOPA administration to male GPR88 KO mice, subjected to unilateral 6-hydroxydopamine (6-OHDA) lesions of the medial forebrain bundle, resulted in more rotations than in their WT counterparts. Conversely, GPR88 KO mice had a lower abnormal involuntary movements (AIMs) score. These behavioral responses were accompanied by altered transcription of L-DOPA upregulated genes in lesioned GPR88 KO compared to WT striata. In accordance with a role for serotonin neurons in LID development, WT but not GPR88 KO striata exhibited 5-hydroxytryptamine displacement upon repeated L-DOPA treatment. Intact male GPR88 KO mice showed diminished tacrine-induced PD-like tremor and spontaneous hyperlocomotion. Dopamine and its metabolites were not increased in male GPR88 KO mice, but biosensor recordings revealed increased spontaneous/basal and evoked glutamate release in striata of male GPR88 KO mice. In conclusion, genetic deletion of GPR88 promotes l-DOPA-induced rotation and spontaneous locomotion yet suppresses the induction of LIDs and also reduces tremor. These data provide behavioral, neurochemical and molecular support that GPR88 antagonism may favour motor relief in PD patients without aggravating the induction of motor side effects.
 ...
PMID:Genetic deletion of GPR88 enhances the locomotor response to L-DOPA in experimental parkinsonism while counteracting the induction of dyskinesia. 3166 99

Hyperkinetic movement disorders include tremors, dystonia, chorea, tics, myoclonus, stereotypies, restless legs syndrome, and various other disorders with abnormal involuntary movements. Although several disorders could be included in such a broad spectrum, a limited number of conditions are modeled in non-human primates. These disabling conditions include notably L-dopa-induced dyskinesia in Parkinson's disease, tardive dyskinesia, essential tremor and Huntington's disease. Non-human primate models of these conditions exist. This short opiniated review surveys the current state of use of these models as well as the future developments.
 ...
PMID:Models of hyperkinetic disorders in primates. 3185 31

Depression is a common comorbid condition in Parkinson's disease (PD). Patients with depression have a two-fold increased risk to develop PD. Further, depression symptoms often precede motor symptoms in PD and are frequent at all stages of the disease. However, the influence of a depressive state on the responses to antiparkinson treatments is largely unknown. In this study, the genetically inbred depression-like flinders sensitive line (FSL) rats and control flinders resistant line (FRL) rats were studied in models of experimental parkinsonism. FSL rats showed a potentiated tremorgenic response to tacrine, a cholinesterase inhibitor used experimentally to induce 6 Hz resting tremor reminiscent of parkinsonian tremor. We also studied rats lesioned with 6-OHDA to induce hemiparkinsonism. No baseline differences in dopaminergic response to acute apomorphine or L-DOPA was found. However, following chronic treatment with L-DOPA, FRL rats developed sensitization of turning and abnormal involuntary movements (AIMs); these effects were counteracted by the anti-dyskinetic 5-HT1 A agonist/D2 partial agonist sarizotan. In contrast, FSL rats did not develop sensitization of turning and only minor AIMs in response to L-DOPA treatment. The roles of several non-dopamine systems underlying this discrepancy were studied. Unexpectedly, no differences of opioid neuropeptides or serotonin markers were found between FRL and FSL rats. The marked behavioral difference between the FRL and FSL rats was paralleled with the striatal expression of the established marker, c-fos, but also the GABAergic transporter (vGAT), and a hitherto unknown marker, tamalin, that is known to regulate mGluR5 receptor function and postsynaptic organization. This study demonstrates that behavioral and transcriptional responses of non-dopaminergic systems to experimental parkinsonism and L-DOPA are modified in a genetic rat model of depression.
 ...
PMID:Non-dopaminergic Alterations in Depression-Like FSL Rats in Experimental Parkinsonism and L-DOPA Responses. 3226 3


<< Previous 1 2 3 4 5