Phospholipase D-catalyzed hydrolysis of phosphatidylcholine provides the choline precursor for acetylcholine synthesis in a human neuronal cell line.

To identify the metabolic pathway that generates choline (Cho) for acetylcholine (AcCho) from its storage pool in membrane phosphatidylcholine (PtdCho), human neuronal cells (LA-N-2) were radioisotopically labeled with 1-O-hexadecyl-2-hydroxy-sn-glycero(3)phospho[14C]choline. The compound was efficiently taken up by the cells and metabolically labelled PtdCho, Cho, AcCho, and phosphocholine pools. In pulse-chase experiments, the specific radioactivities of the metabolites of 1-O-hexadecyl-2-hydroxy-sn-glycero(3)-phospho[14C]choline indicated that it was rapidly acylated to Ptd-Cho and then hydrolyzed first to free Cho and not to phosphocholine or glycerophosphocholine. This Cho was subsequently converted to AcCho and to phosphocholine. In the absence of exogenous Cho, at least 15% of the total cellular AcCho pool was synthesized by this pathway in 1 h. The data demonstrate that the liberation of the free Cho precursor for AcCho synthesis from PtdCho can be accomplished in a one-step process, indicating the involvement of a phospholipase D-type enzyme. In the presence of hemicholinium-3, which inhibits Cho transport, the amount of intracellular [14C]Cho metabolites that accumulated during the chase period was higher than in control cells, indicating that PtdCho hydrolysis liberated Cho directly into the cytoplasm. These data show that cholinergic cells are characterized by an intracellular pathway, catalyzed by a phospholipase D, that generates Cho for AcCho synthesis from PtdCho. Abnormalities in the regulation of this pathway may contribute to selective vulnerability of cholinergic neurons in certain neurodegenerative diseases, e.g., Alzheimer disease.

An evaluation of the clinical utility of the Draw-a-Person Test.

Evaluated the reliability and validity of objective scoring procedures on the Draw-A-Person Test. Handler's (1967) scales and other ratings of overall quality were used. Ss were mentally retarded persons, hospitalized and non-hospitalized psychotics, and normals. Naive raters scored the protocols under blind conditions. Reliability estimates for both sets of scales ranged from .42 to .78. Positive evidence also is presented, which indicates that overall quality does relate to overall level of psychological adjustment. Group and scale differences are discussed.

Hemispheric dysfunction in schizophrenia: assessment by visual perception tasks.

Before and after a double-blind trial of haloperidol vs. mesoridazine, 24 hospitalized schizophrenics performed visual perception tasks designed to assess function of the cerebral hemispheres. Tasks involved identifying as "same" or "different" two images (either letters, digits, or unfamiliar shapes) projected tachistoscopically to the right or left visual field or to both together. Multivariate analysis of variance related response latency and accuracy to task type, hemisphere stimulated, and pre- vs. posttreatment testing. Both before and after treatment, subjects responded most slowly and least accurately to letter-matching. Bilateral presentation of stimuli resulted in faster and more accurate responses, except on shape-matching. Neuroleptic treatment improved speed and accuracy overall, though not under certain task conditions. Results accorded more with an impairment in verbal processing and interhemispheric coordination than with a specific left-hemispheric deficit in schizophrenia.

Auditory attention in process and reactive schizophrenia.

The present data indicate that, based on level of premorbid adjustment (process-reactive), schizophrenic subjects differ in auditory attention processes. Generally speaking, poor premorbid adjustment is associated with more attention dysfunction. Results also indicate that attentional deficits improve for all schizophrenic subjects after a 28-day period of neuroleptic therapy.