Question

Segawa syndrome is a genetic mutation that affects the synthesis of dopamine in the body. People with this disorder walk clumsily and have involuntary muscle contractions. Please draw a diagram representing the pathway of neurons involved in segawa syndrome, label the following feature: CNS- central nervous system, spinal nerve, cell body, axon, dendrites, affected organ, afferent pathway, efferent pathway, interneuron, sensory neuron, motor neuron, and synapse.

Answer 1

Segawa Syndrome (SS) also known as Dopamine-responsive dystonia (DRD), Segawa's disease, Segawa's dystonia and hereditary progressive dystonia with diurnal fluctuation, is a genetic movement disorder which usually manifests itself during early childhood at around ages 5–8 years (variable start age).

Characteristic symptoms are increased muscle tone (dystonia, such as clubfoot) and Parkinsonian features, typically absent in the morning or after rest but worsening during the day and with exertion. Children with SS are often misdiagnosed as having cerebral palsy. The disorder responds well to treatment with levodopa.

Now Your answers-
a. Autosomal dominant and autosomal recessive forms of the disease have been reported. Mutations in several genes have been shown to cause dopamine-responsive dystonia. The precursor of the neurotransmitter dopamine, l-dopa, is synthesised from tyrosine by the enzyme tyrosine hydroxylase and utilises tetrahydrobiopterin (BH4) as a cofactor. A mutation in the gene GCH1, which encodes the enzyme GTP cyclohydrolase I, disrupts the production of BH4, decreasing dopamine levels (hypodopaminergia). This results in autosomal-dominant SS. Mutations in the genes for tyrosine hydroxylase and sepiapterin reductase result in autosomal-recessive forms of the disease. When the latter enzyme is affected, the condition tends to be more severe. The activity of dopaminergic neurons in the nigrostriatal pathway which are parts of BASAL GANGLIA  normally peaks during the morning and also decreases with age until after age 20, which explains why the symptoms worsen during the course of the day and with increasing age until the third decade of life.

b. The direct pathway is involed which is originating in the dorsal striatum inhibits the GPi and SNr, resulting in a net disinhibition or excitation of the thalamus. This pathway consist of medium spiny neurons(MSNs) that express dopamine receptor D1, muscarinic acetylcholine receptor M4, and adenosine receptor A1. The direct pathway has been proposed to facilitate motor actions, timing of motor actions, gating of working memory, and motor responses to specific stimuli.

Lets first understand the Basal Ganglia ... I am posting my hand written explanation of this....

this was the exact pathway of the Segawa's Syndrome the DIRECT PATHWAY .....

I hope you have understand the pathways.............
see labeling of cell body, axon, ect is very easy ... what is difficult is the efferent, afferent and other dopaminergic pathways which i have shown you .....

c. This simplified image will show the whole thing .....

Now I think all concepts about the synapses are clear.....

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