Abstract:
:The cytotoxic effects of DL-, D- and L-alpha-aminoadipic acid, a six-carbon homologue of glutamate, were investigated in cell cultures of dissociated postnatal mouse cerebellum. Treatment with alpha-aminoadipic acid resulted in rapid nuclear and cytoplasmic swelling and, after longer periods of exposure, karyopyknosis of astrocytes, identified by indirect immunofluorescence labelling with anti-human glial fibrillary acidic protein antiserum. The number of astrocytes with pyknotic nuclei depended on the concentration of alpha-aminoadipic acid as well as on the duration of drug action. The presence of 0.21 mM DL-alpha-aminoadipic acid or 0.10 mM L-alpha-aminoadipic acid for 40 h caused karyopyknosis in 50% of the astrocytes. In contrast, D-alpha-aminoadipic acid, had little gliotoxic activity. None of the cytotoxic effects of DL-alpha-aminoadipic acid or L-alpha-aminoadipic acid observed 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 alpha-aminoadipic acid was included in the culture medium at plating. These results indicate that alpha-adminoadpic acid can be used to substantially reduce the number of astroglia in cerebellar cultures and that dissociated cell cultures will provide a useful model with which to study the mechanisms of alpha-aminoadipic acid induced glial toxicity.
journal_name
Neurosciencejournal_title
Neuroscienceauthors
Huck S,Grass F,Hatten MEdoi
10.1016/0306-4522(84)90170-2subject
Has Abstractpub_date
1984-07-01 00:00:00pages
783-91issue
3eissn
0306-4522issn
1873-7544pii
0306-4522(84)90170-2journal_volume
12pub_type
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