Reference

Gliotoxic effects of a-aminoadipic acid on monolayer cultures of dissociated postnatal mouse cerebellum

Gliotoxic effects of a-aminoadipic acid on monolayer cultures of dissociated postnatal mouse cerebellum. Huck, S.; Grass, F.; Hatten, M. E. (Dep. Neuropharmacol., Univ. Vienna, Vienna A-1090, Austria). Neuroscience (Oxford), 12(3), 783-91 (English) 1984. CODEN: NRSCDN. ISSN: 0306-4522. DOCUMENT TYPE: Journal CA Section: 4 (Toxicology) The cytotoxic effects of DL- [626-71-1], D- [7620-28-2], and L-a-aminoadipic acid [1118-90-7] were investigated in cell cultures of dissocd. postnatal mouse cerebellum. Treatment with a-aminoadipic acid resulted in rapid nuclear and cytoplasmic swelling and, after longer periods of exposure, karyopyknosis of astrocytes, identified by indirect immunofluorescence labeling with antihuman glial fibrillary acidic protein antiserum. The no. of astrocytes with pyknotic nuclei depended on the concn. of a-aminoadipic acid as well as on the duration of drug action. The presence of 0.21 mM DL-a-aminoadipic acid or 0.10 mM L-a-aminoadipic acid for 40 h caused karyopyknosis in 50% of the astrocytes. In contrast, D-a-aminoadipic acid, had little gliotoxic activity. None of the cytotoxic effects of DL- or L-a-aminoadipic acids obsd. for astrocytes were seen for the neurons present in the cultures when the drug was added after 4 days in vitro. Neurotoxic effects were evident, however, when a-aminoadipic acid was included in the culture medium at plating. Thus, a-aminoadipic acid can be used to substantially reduce the no. of astroglia in cerebellar cultures and dissocd. cell cultures will provide a useful model with which to study the mechanisms of a-aminoadipic acid-induced glial toxicity.

A comparison of the effects of isomers of alpha-aminoadipic acid and 2-amino-4-phosphonobutyric acid on the light response of the Mueller glial cell and the electroretinogram

A comparison of the effects of isomers of alpha-aminoadipic acid and 2-amino-4-phosphonobutyric acid on the light response of the Mueller glial cell and the electroretinogram. Zimmerman, R. P.; Corfman, T. P. (Dep. Neurol. Sci., Rush Med. Coll., Chicago, IL 60612, USA). Neuroscience (Oxford), 12(1), 77-84 (English) 1984. CODEN: NRSCDN. ISSN: 0306-4522. DOCUMENT TYPE: Journal CA Section: 2 (Mammalian Hormones) Intracellular recordings of the light response of mudpuppy (Necturus maculosus) retinal Mueller glial cells revealed differential effects of optical isomers of a-aminoadipic acid (I), a putative gliotoxin. L-I [1118-90-7] preferentially abolished the on component but not the off component of the intracellularly recorded Mueller cell light response, abolished the b-wave but not the d-wave of the electroretinogram, and caused histol. damage to the Mueller cells. D-I [7620-28-2] preferentially reduced the off component of the Mueller cell light response and the d-wave of the electroretinogram, and did not cause appreciable histol. damage to the Mueller cells. 2-Amino-4-phosphonobutyric acid [6323-99-5], which has been shown to act preferentially at the synapse of photoreceptors onto depolarizing bipolar cells in the mudpuppy retina, abolished the on response of Mueller cells and the b-wave of the electroretinogram, but caused no histol. damage to the Mueller glial cells. None of the agents caused a significant change in the resting membrane potential of the glial cells. The similarity of the elec. effects of L-I and 2-amino-4-phosphonobutyric acid suggests that the initial loss of the b-wave following L-I treatment is due to action of the amino acid at a synaptic site via a mechanism distinct from that which causes subsequent histol. damage to the glial cells.