New Directions in Neuroscience

In the November 1, 2001 issue, the Journal of Neuroscience inaugurated a new series of critical minireviews called "New Directions in Neuroscience," meant to help readers stay in touch with new methods and new fields of research (Shepherd, 2001). The first set of minireviews is entitled "Genomics and Proteomics," and three of the five reviews treat topics relevant to biological psychology.

"Genomics" refers to the attempt to determine the DNA sequence for all the genes contained in an organism's genome. "Proteomics," sometimes called "functional genomics," is the attempt to determine the function of all the proteins encoded in an organism's complete genome. Learning the sequence of amino acids specified by the gene does not tell us exactly how the amino acids will fold together or how the finished protein will function; these are the questions tackled by proteomics. An overview of these topics and the five minireviews is given by the organizer of this section (Bloom, 2001).

The first of the reviews to be considered briefly here, "Proteomics in neuroscience: From protein to network" (Grant and Blackstock, 2001), discusses the technology of proteomics and its applications to the nervous system. Ion channels and neurotransmitter subunits are known to be subject to regulatory phosphorylation – the addition of phosphate groups to a protein. Identification of phosphorylation sites on various proteins has long been performed by radioisotope labeling, but mass spectrometry is now replacing it. Identifying the presence of proteins in key compartments within neurons and glial cells will provide a framework for understanding function. Next will come the study of intracellular clusters and networks of proteins of similar or related functions and determining how they contribute to neural circuits and the regulation of behavior.

A review entitled "Physiological genomics of antidepressant targets: Keeping the periphery in mind" (Blakeley, 2001) considers the membrane transporters that accomplish reuptake of released serotonin and norepinephrine (NE) back into the presynaptic junction. The serotonin transporters (SERTs) and NE transporters (NETs) interact with many drugs that are active in the CNS, including multiple classes of antidepressants such as the serotonin-selective reuptake inhibitors (e.g., fluoxetine [Prozac]) and more recently developed NE-selective transporter antagonists.

After the human NET gene was isolated and mapped, investigators looked for associations between it and several psychiatric disorders but with little effect to date. The author suggests that, since a single gene encodes NETs in both the central and peripheral nervous systems, it may be simpler for the present to study it in the periphery, such as in control of heart rate and other cardiovascular conditions. Similarly, studies exploring the roles of SERTs in psychiatric disorders may benefit from considering the important roles of serotonin in gastrointestinal functioning.

The last of this set of minireviews is entitled "Psychogenomics: Opportunities for understanding addiction" (Nestler, 2001). By "psychogenomics," the author means the application of the powerful tools of genomics and proteomics to better understand the biological substrates of normal behavior and of diseases of the brain that manifest themselves as behavioral abnormalities. He is specifically interested in drug abuse and hopes that psychogenomics will help to identify (a) genes that confer risk for addiction, and (b) genes and proteins that contribute to the regulation of reward, motivation, and cognition under normal circumstances and to abnormalities that characterize an addicted state.

Two major approaches have been used to study genetic causes of addiction. One is the "candidate gene" approach, studying genes or proteins implicated in pathophysiology or in animal models. The other approach is open-ended and involves genome-wide scans of affected and unaffected individuals. The importance of the latter approach is that several neuropsychiatric disorders appear to involve genes that never would have been considered candidates. Furthermore, the open-ended approach is becoming steadily more feasible technically. Within the complex field of studying brain function, Nestler suggests that the field of addiction may lead the way because of the relative ease of relating molecular events to meaningful animal models and to human disorders.

References:

Blakely, R.D. (2001). Physiological genomics of antidepressant targets: Keeping the periphery in mind. Journal of Neuroscience, 21(21), 8319-8323.

Bloom, F.E. (2001). What does it all mean to you? Journal of Neuroscience, 21(21), 8304-8305.

Grant, S.G.N. and Blackstock, W.P. (2001). Proteomics in neuroscience: From protein to network. Journal of Neuroscience, 21(21), 8315-8318.

Nestler, E.J. (2001). Psychogenomics: Opportunities for understanding addiction. Journal of Neuroscience, 21(21), 8324-8327.

Shepherd, G.M. (2001). A new feature for the Journal of Neuroscience: New Directions in Neuroscience. Journal of Neuroscience, 21(21), 8303.