Plant-derived neurotoxic amino acids (beta-N-oxalylamino-L-alanine and beta-N-methylamino-L-alanine): effects on central monoamine neurons.
In the present study the subacute effects of beta-N-oxalylamino-L-alanine (BOAA) and beta-N-methylamino-L-alanine (BMAA) on CNS monoamine neurons in rats were investigated following intracisternal injections or local intracerebral administration into substantia nigra. In vitro effects of BOAA and BMAA on high-affinity synaptosomal uptake of dopamine (DA), noradrenaline (NA), and serotonin (5-HT) were also examined. Intracisternal administration of BMAA decreased NA levels in hypothalamus, whereas no effects were seen on DA or 5-HT levels. Following intranigral injections of BOAA, NA levels tended to decrease in several regions, whereas the DA levels and the levels of DA metabolites were unaffected in all regions analyzed. Loss of tyrosine hydroxylase (TH) immunoreactivity in the intranigral injection sites and the presence of TH-immunoreactive pyknotic neurons near the borders of the injection sites were observed following both BOAA and BMAA treatments. Furthermore, substance P-immunoreactive terminals in substantia nigra pars reticulata were also found to have disappeared within the lesioned area following either BOAA or BMAA injections. Incubations with both BOAA and BMAA (10(-5) M) reduced high-affinity [3H]NA uptake in cortical synaptosomes to 69% and 41% of controls, respectively, whereas the striatal high-affinity [3H]DA uptake and the cortical high-affinity [3H]5-HT uptake were unaffected by BOAA or BMAA. The results demonstrate that both BOAA and BMAA can affect central monoamine neurons, although the potency and specificity of these substances on monoamine neurons when administered acutely into cerebral tissue or liquor cerebri seem to be low. However, the in vitro studies indicate selective effects of both compounds on NA neurons in synaptosomal preparations.
Lindström
H
H
Department of Histology and Neurobiology, Karolinska Institute, Stockholm, Sweden.
Luthman
J
J
Mouton
P
P
Spencer
P
P
Olson
L
L
D000409:Alanine / Q000031:analogs & derivatives*; D000599:Amino Acids, Diamino / Q000494:pharmacology*; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D000087522:Cyanobacteria Toxins; D004298:Dopamine / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009498:Neurotoxins / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000599:Amino Acids, Diamino; D015306:Biogenic Monoamines; D000087522:Cyanobacteria Toxins; D009498:Neurotoxins; C001824:beta-N-methylamino-L-alanine; D015091:beta-Alanine; C100126:oxalyldiaminopropionic acid; D012701:Serotonin; D014446:Tyrosine 3-Monooxygenase; D000409:Alanine; D004298:Dopamine; D009638:Norepinephrine