Cyclin-Dependent Kinase 5 in the Ventral Tegmental Area Regulates Depression-Related Behaviours

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Cyclin-Dependent Kinase 5 in the Ventral Tegmental Area Regulates Depression-Related Behaviours

Dopamine

Ventral Tegmental Area (VTA)

Cyclin-Dependent Kinase 5 in the Ventral Tegmental Area Regulates Depression-Related Behaviours

Depression-related Behaviours

Cyclin-dependent Kinase 5 (Cdk5)

One of the most prevalent theories of depression is the monoamine hypothesis which postulates that a deficiency of monoamines, like dopamine, leads to depression. Leading from this, researchers have shown that altering the dopaminergic neurons from the ventral tegmental area (VTA) can affect the presence of depression-related symptoms, suggesting the malfunction of these neurons may cause depression.

This lead to the idea of knocking out cyclin-dependent kinase 5 (Cdk5), a serine/threonine kinase with many functions, in the VTA. Cdk5 phosphorylates the enzyme tyrosine hydroxylase, used in dopamine synthesis, both directly and indirectly using a cAMP/PKA/CREB system. The researchers found that mice that had Cdk5 function knocked out showed depression-like behaviour.

Cyclic AMP (cAMP)

Researchers also found decreased levels of cyclic AMP (cAMP) in the VTA of the mice with Cdk5 function knocked out. Furthermore, they were able to reverse the depression-related behaviours by increasing levels of cAMP in the VTA. These findings suggest that Cdk5 has a role in causing depression-related behaviours by altering dopamine levels in the VTA using a cAMP pathway.

Media Cited in this Glog:VTA/NAc/PFC diagram: http://www.drugabuse.gov/sites/default/files/slide-9.gifCdk5 protein structure: http://upload.wikimedia.org/wikipedia/commons/thumb/7/79/PBB_Protein_CDK5_image.jpg/250px-PBB_Protein_CDK5_image.jpgcAMP structure: http://www.bioxys.com/i_asssaydesign/image/48_diagram_1.gifResults figure: Zhong P., Liu, X., Zhang, Z., Hu Y., Liu S.J., Lezama-Ruiz, M., Joksimovic, M., ' Liu, Q.S. (2014) Cyclin-dependent kinase 5 in the ventral tegmental area regulates depression-related behaviours. Journal of Neuroscience, 34(18): 6352-6366.


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