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Protein Z Deficiency

ACTSCI-JPZISM

Neurotransmitters like Serotonin and Dopamine play a role in the modulation of mood. A detailed investigation of the pattern of this association has assumed great significance with studies indicating an association between these chemicals and suicidal tendency.

A study was undertaken to investigate the details of the roles of neurotransmitters in mood disturbances, specifically depression. People were examined to find if they were suffering from depression, and samples of their cerebrospinal fluids were taken to measure the levels of neurotransmitters. Cerebrospinal fluid (CSF) is a protective nourishing fluid that circulates around the brain and spinal cord of the central nervous system.

1,000 people were examined and their CSF samples analyzed to determine the levels of Serotonin. The results are tabulated below.

Table 1

Depression present Depression not present
Serotonin level low in CSF 90 90
Serotonin level normal in CSF 10 810

CSF samples of the same 1000 people were analyzed to determine the levels of Dopamine. The results are given in table 7.2.

Table 2

Depression present Depression not present
Dopamine level low in CSF 70 150
Dopamine level normal in CSF 30 750

To define the exact roles of the abnormal levels of various neurotransmitters in causation of depression, experiments were conducted on mice that showed signs and symptoms of depression.

Experiment 1

100 mice that showed signs and symptoms of depression were given exogenous serotonin. 90 of these showed an improvement.

Experiment 2

Serotonin is metabolized in the body mainly by liver. An enzyme monoamine oxidase first converts it into an aldehyde; and then aldehyde dehydrogenase converts this aldehyde to 5-hydroxyindoleacetic acid (5-HIAA).

The mice that did not respond to exogenous Serotonin in experiment 1 were administered 5-HIAA. Five of these showed an improvement.

Experiment 3

The 90 mice that showed improvements in the first experiment were not administered any further doses of Serotonin. Starting from the first animal at 7 days, all of them developed signs and symptoms of depression by the 30th day. On the 31st day, they were administered exogenous 5-HIAA. All of them showed an improvement.

Further studies demonstrated a deficiency of protein “Z” in the brain cells of patients suffering from depression. Patients of depression with a deficiency of protein “Z” also had low levels of Dopamine and Serotonin.

Administration of isolates of protein “Z” from transgenic mice resulted in increase in the levels of Serotonin and Dopamine in these patients. 70% of people had a history of depression in the family. In 50% of these cases, at least one unaffected (by depression) family member had a deficiency of protein “Z”.

Which of these if fully developed would provide the best treatment option in such cases?

A

Gene therapy

B

Co-administration of monoamine oxidase and aldehyde dehydrogenase

C

Administration of Dopamine, Serotonin and 5-HIAA

D

Administration of 5-HIAA