Block of slow axonal transport and axonal growth by brefeldin A in compartmented cultures of rat sympathetic neurons.

Disruption of the Golgi by brefeldin A (BFA) has been reported to block fast axonal transport and axonal growth. We used compartmented cultures of rat sympathetic neurons to investigate its effects on slow axonal transport. BFA (1 micro g/ml) applied to cell bodies/proximal axons for 6-20 h disrupted the Golgi, reversibly blocked axonal growth, and reversibly blocked anterograde transport of all proteins, including tubulin. The retrograde transport of nerve growth factor (NGF) was also blocked. The phosphorylation of Erk1 and Erk2 in response to NGF was unaffected after 6 h of treatment with BFA, suggesting that the block of axonal transport was specific and direct. Consistent with its principal site of action at the Golgi, no effects were observed when BFA was applied only to the distal axons. Block of fast anterograde and retrograde axonal transport is consistent with the role of the Golgi in supplying transport vesicles. Block of slow axonal transport was surprising, and further results indicated that transport of tubulin en route along the axon was arrested by application of BFA to the cell bodies, suggesting that a continuous supply of anterograde transport vesicles from the Golgi is required to maintain slow axonal transport of cytoskeletal proteins.

Male sterility associated with APRT deficiency in Arabidopsis thaliana results from a mutation in the gene APT1.

Four mutants of Arabidopsis thaliana that are deficient in adenine phosphoribosyl transferase (APRT) activity have been isolated by selecting for germination of seeds and growth of the plantlets on a medium containing 2,6-diaminopurine (DAP), a toxic analog of adenine. In all mutants, DAP resistance is due to a recessive nuclear mutation at a locus designated apt. The mutants are male sterile due to pollen abortion after meiosis. Furthermore, it has been shown that metabolism of cytokinins is impaired in the mutant BM3, which has the lowest level of APRT activity among the mutants tested. However, three different cDNAs encoding APRT have been isolated in A. thaliana and this raised the question of the nature of the mutation which results in low APRT activity. The mutation was genetically mapped to chromosome I and lies within 6 cM of the phenotypic marker dis2, indicating that the mutation affects the APT1 gene, a result confirmed by sequencing of mutant alleles. The mutation in the allele apt1-3 is located at the 5' splicing site of the third intron, and eliminates a BstNI restriction site, as verified by Southern blotting and PCR fragment length analysis.

Effect of fenfluramine on mood: a double-blind placebo-controlled trial.

Depressed patients (n = 10), schizophrenics (n = 6), and normal control subjects was (n = 9) were administered fenfluramine hydrochloride (FF) (60 mg/os) or placebo in the context of a randomized, double-blind crossover trial. No effect of FF on mood or activation was detected over a 6-hr period. A previous report claiming acute antidepressant effects of FF in depressed subjects was not confirmed.

Neuroendocrine responses in chronic schizophrenia. Evidence for serotonergic dysfunction.

Neuroendocrine and mood responses to a 60 mg oral dose of the serotonin-releasing agent, fenfluramine, were assessed in ten neuroleptic-free, chronic schizophrenic patients and in age- and sex-matched normal control subjects. The prolactin (PRL) response to fenfluramine was significantly blunted in the schizophrenic subjects. Growth hormone and cortisol levels were not differentially affected by the challenge. There was no significant effect of fenfluramine on mood in either group. The blunted PRL response in the schizophrenic group suggests serotonergic dysfunction; possible mechanisms of this finding and implications for treatment are considered.