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Levodopa-induced Dyskinesia
Levodopa-induced dyskinesia (LID) is a form of dyskinesia associated with levodopa (l-DOPA), used to treat Parkinson's disease. It often involves hyperkinetic movements, including chorea, dystonia, and athetosis. In the context of Parkinson's disease (PD), dyskinesia is often the result of long-term dopamine therapy. These motor fluctuations occur in up to 80% of PD patients after 5–10 years of l-DOPA treatment, with the percentage of affected patients increasing over time. Based on the relationship with levodopa dosing, dyskinesia most commonly occurs at the time of peak l-DOPA plasma concentrations and is thus referred to as peak-dose dyskinesia (PDD). As patients advance, they may present with symptoms of diphasic dyskinesia (DD), which occurs when the drug concentration rises or falls. If dyskinesia becomes too severe or impairs the patient's quality of life, a reduction in l-Dopa might be necessary, however this may be accompanied by a worsening of motor performance. There ...
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Neurology
Neurology (from el, wikt:νεῦρον, νεῦρον (neûron), "string, nerve" and the suffix wikt:-logia, -logia, "study of") is the branch of specialty (medicine), medicine dealing with the diagnosis and treatment of all categories of conditions and disease involving the brain, the spinal cord and the peripheral nerves. Neurological practice relies heavily on the field of neuroscience, the scientific study of the nervous system. A neurologist is a physician specializing in neurology and trained to investigate, diagnose and treat neurological disorders. Neurologists treat a myriad of neurologic conditions, including stroke, seizures, movement disorders such as Parkinson's disease, autoimmune neurologic disorders such as multiple sclerosis, headache disorders like migraine and dementias such as Alzheimer's disease. Neurologists may also be involved in clinical research, clinical trials, and basic research, basic or translational research. While neurology is a nonsurgical sp ...
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Nigrostriatal Pathway
The nigrostriatal pathway is a bilateral dopaminergic pathway in the brain that connects the substantia nigra pars compacta (SNc) in the midbrain with the dorsal striatum (i.e., the caudate nucleus and putamen) in the forebrain. It is one of the four major dopamine pathways in the brain, and is critical in the production of movement as part of a system called the basal ganglia motor loop. Dopaminergic neurons of this pathway release dopamine from axon terminals that synapse onto GABAergic medium spiny neurons (MSNs), also known as spiny projection neurons (SPNs), located in the striatum. Degeneration of dopaminergic neurons in the SNc is one of the main pathological features of Parkinson's disease, leading to a marked reduction in dopamine function and the symptomatic motor deficits of Parkinson's disease including hypokinesia, tremors, rigidity, and postural imbalance. Anatomy The connection between the substantia nigra pars compacta and the dorsal striatum is mediated via dopa ...
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Globus Pallidus
The globus pallidus (GP), also known as paleostriatum or dorsal pallidum, is a subcortical structure of the brain. It consists of two adjacent segments, one external, known in rodents simply as the globus pallidus, and one internal, known in rodents as the entopeduncular nucleus. It is part of the telencephalon, but retains close functional ties with the subthalamus in the diencephalon – both of which are part of the extrapyramidal motor system. The globus pallidus is a major component of the basal ganglia, with principal inputs from the striatum, and principal direct outputs to the thalamus and the substantia nigra. The latter is made up of similar neuronal elements, has similar afferents from the striatum, similar projections to the thalamus, and has a similar synaptology. Neither receives direct cortical afferents, and both receive substantial additional inputs from the intralaminar thalamus. Globus pallidus is Latin for "pale globe". Structure Pallidal nuclei are ma ...
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Subthalamic Nucleus
The subthalamic nucleus (STN) is a small lens-shaped nucleus in the brain where it is, from a functional point of view, part of the basal ganglia system. In terms of anatomy, it is the major part of the subthalamus. As suggested by its name, the subthalamic nucleus is located ventral to the thalamus. It is also dorsal to the substantia nigra and medial to the internal capsule. It was first described by Jules Bernard Luys in 1865, and the term ''corpus Luysi'' or ''Luys' body'' is still sometimes used. Anatomy Structure The principal type of neuron found in the subthalamic nucleus has rather long, sparsely spiny dendrites. In the more centrally located neurons, the dendritic arbors have a more ellipsoidal shape. The dimensions of these arbors (1200 μm, 600 μm, and 300 μm) are similar across many species—including rat, cat, monkey and human—which is unusual. However, the number of neurons increases with brain size as well as the external dimensions of th ...
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Deep Brain Stimulation
Deep brain stimulation (DBS) is a neurosurgical procedure involving the placement of a medical device called a neurostimulator, which sends electrical impulses, through implanted electrodes, to specific targets in the brain (the brain nucleus) for the treatment of movement disorders, including Parkinson's disease, essential tremor, dystonia, and other conditions such as obsessive-compulsive disorder (OCD) and epilepsy. While its underlying principles and mechanisms are not fully understood, DBS directly changes brain activity in a controlled manner. DBS has been approved by the Food and Drug Administration as a treatment for essential tremor and Parkinson's disease (PD) since 1997. DBS was approved for dystonia in 2003, obsessive–compulsive disorder (OCD) in 2009, and epilepsy in 2018. DBS has been studied in clinical trials as a potential treatment for chronic pain for various affective disorders, including major depression. It is one of few neurosurgical procedures that ...
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Management Of Parkinson's Disease
In the management of Parkinson's disease, due to the chronic nature of Parkinson's disease (PD), a broad-based program is needed that includes patient and family education, support-group services, general wellness maintenance, exercise, and nutrition. At present, no cure for the disease is known, but medications or surgery can provide relief from the symptoms. While many medications treat Parkinson's, none actually reverses the effects of the disease. Furthermore, the gold-standard treatment varies with the disease state. People with Parkinson's, therefore, often must take a variety of medications to manage the disease's symptoms. Several medications currently in development seek to better address motor fluctuations and nonmotor symptoms of PD. However, none is yet on the market with specific approval to treat Parkinson's. Medication The main families of drugs useful for treating motor symptoms are levodopa, dopamine agonists, and MAO-B inhibitors. The most commonly used treatm ...
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Antiepileptic
Anticonvulsants (also known as antiepileptic drugs or recently as antiseizure drugs) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder and borderline personality disorder, since many seem to act as mood stabilizers, and for the treatment of neuropathic pain. Anticonvulsants suppress the excessive rapid firing of neurons during seizures. Anticonvulsants also prevent the spread of the seizure within the brain. Conventional antiepileptic drugs may block sodium channels or enhance γ-aminobutyric acid ( GABA) function. Several antiepileptic drugs have multiple or uncertain mechanisms of action. Next to the voltage-gated sodium channels and components of the GABA system, their targets include GABAA receptors, the GAT-1 GABA transporter, and GABA transaminase. Additional targets include voltage-gated calcium channels, SV2A, and α2δ. By blocking sodium or calc ...
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Levetiracetam
Levetiracetam, sold under the brand name Keppra among others, is a medication used to treat epilepsy. It is used for partial-onset, myoclonic, or tonic–clonic seizures and is taken either by mouth as an immediate or extended release formulation or by injection into a vein. Common side effects of levetiracetam include sleepiness, dizziness, feeling tired, and aggression. Severe side effects may include psychosis, suicide, and allergic reactions such as Stevens–Johnson syndrome or anaphylaxis. It is unclear if levetiracetam is safe for use during pregnancy and breastfeeding. Levetiracetam is the S-enantiomer of etiracetam. Its mechanism of action is not yet clear. Levetiracetam was approved for medical use in the United States in 1999 and is available as a generic medication. In 2020, it was the 92nd most commonly prescribed medication in the United States, with more than 7million prescriptions. Medical uses Focal epilepsy Levetiracetam is effective as single-drug treat ...
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Animal Models Of Parkinson's Disease
Animal models of Parkinson's disease are essential in the research field and widely used to study Parkinson's disease. Parkinson's disease is a neurodegenerative disorder, characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The loss of the dopamine neurons in the brain, results in motor dysfunction, ultimately causing the four cardinal symptoms of PD: tremor, rigidity, postural instability, and bradykinesia. It is the second most prevalent neurodegenerative disease, following Alzheimer's disease. It is estimated that nearly one million people could be living with PD in the United States. There are a variety of models that can be utilized to be able to address important aspects of Parkinson's disease. Researchers can consider disease progression, cell death, behavioral characteristics, and more PD phenotypes. Parkinson's disease animal models are divided into two categories: neurotoxin models and genetic models. Neurotoxin models include ...
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Viral Vectors
Viral vectors are tools commonly used by molecular biologists to deliver genetic material into cells. This process can be performed inside a living organism (''in vivo'') or in cell culture (''in vitro''). Viruses have evolved specialized molecular mechanisms to efficiently transport their genomes inside the cells they infect. Delivery of genes or other genetic material by a vector is termed transduction and the infected cells are described as transduced. Molecular biologists first harnessed this machinery in the 1970s. Paul Berg used a modified SV40 virus containing DNA from the bacteriophage λ to infect monkey kidney cells maintained in culture. In addition to their use in molecular biology research, viral vectors are used for gene therapy and the development of vaccines. Key properties of a viral vector VIRAL VECTORS are tailored to their specific applications but generally share a few key properties. *''Safety'': Although viral vectors are occasionally created from pathoge ...
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ΔFosB
Protein fosB, also known as FosB and G0/G1 switch regulatory protein 3 (G0S3), is a protein that in humans is encoded by the FBJ murine osteosarcoma viral oncogene homolog B (''FOSB'') gene. The FOS gene family consists of four members: FOS, FOSB, FOSL1, and FOSL2. These genes encode leucine zipper proteins that can dimerize with proteins of the JUN family (e.g., c-Jun, JunD), thereby forming the transcription factor complex AP-1. As such, the FOS proteins have been implicated as regulators of cell proliferation, differentiation, and transformation. FosB and its truncated splice variants, ΔFosB and further truncated Δ2ΔFosB, are all involved in osteosclerosis, although Δ2ΔFosB lacks a known transactivation domain, in turn preventing it from affecting transcription through the AP-1 complex. The ΔFosB splice variant has been identified as playing a central, ''crucial'' (necessary and sufficient) role in the development and maintenance of addiction. ΔFosB overexpression ...
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Dopamine Receptor D1
Dopamine receptor D1, also known as DRD1. It is one of the two types of D1-like receptor family - receptors D1 and D5. It is a protein that in humans is encoded by the DRD1 gene. Tissue distribution D1 receptors are the most abundant kind of dopamine receptor in the central nervous system. Northern blot and in situ hybridization show that the mRNA expression of DRD1 is highest in the dorsal striatum ( caudate and putamen) and ventral striatum (nucleus accumbens and olfactory tubercle). Lower levels occur in the basolateral amygdala, cerebral cortex, septum, thalamus, and hypothalamus. Function D1 receptors regulate the memory, learning, and the growth of neurons, also is used in the reward system and locomotor activity, mediating some behaviors and modulating dopamine receptor D2-mediated events. They play a role in addiction by facilitating the gene expression changes that occur in the nucleus accumbens during addiction. They are Gs/a coupled and can stimulate neuron ...
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