Introduction

It has been 50 years since Tallan et al.1 detected W-acetyl aspartate (NAA) in cat brain extracts, and 40 years since Curatolo et al.2 reported the presence of W-acetyl aspartyl glutamate (NAAG) in horse brain. One of the major barriers to the discovery of these two moieties in brain was that they were W-blocked, thereby preventing the ready detection with ninhydrin reactivity, a common method for measuring amino acids. Tallan et al.1 separated protein free extracts of cat brain over a Dowex ion exchange column and demonstrated that a late eluting ninhydrin negative fraction became positive after acid hydrolysis, thereby discovering N-acetyl aspartate. A decade later, Curatolo et al.2 found that subsequent eluted fractions, also ninhydrin negative, contained aspartate and glutamate after acid hydrolysis, thereby disclosing the existence of NAAG. He also was able to demonstrate an uneven regional distribution of NAAG in brain that provided a hint of potential physiologic significance. These discoveries antedated by a decade or more the identification of trace neuropeptides in brain such as the enkephalins3 and somatostatin.4 Ironically, research on NAA and NAAG did not commence in earnest until the mid 1980s.5-7

It is indeed odd that the first symposium dedicated to these two moieties has been so long in taking place. The lack of attention to NAA and NAAG is reminiscent of Rodney Dangerfield's complaint: "I can't get no respect." In support of this contention, one might compare NAA and NAAG to somatostatin and enkephalin. Since its discovery in 1956, NAA, with a brain concentration of 3 mM, has been the topic 1759 publications. NAAG, discovered in 1965 with a concentration of 0.2 mM in rat cortex, undoubtedly the most abundant neuropeptide in cortex, is addressed in 282 publications. In contrast, enkephalin, discovered in 19753 with a 200 nM concentration in rat cortex, has received 16,448 publications; and somatostatin, discovered in 19724 with a 10 nM concentration in rat cortex, has been included in 21,866 publications. Thus, the universe of scientists involved in

Department of Psychiatry and Neuroscience, Harvard Medical School, McLean Hospital, 115 Mill St, Belmont MA 02178-9106 USA, 617-855-2101, Fax: 617-855-2705, E-mail [email protected]

research on NAA and NAAG is rather small; and fortunately, most are participating in this conference.

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