THE DEVELOPMENT OF STRIATAL PATCH MATRIX ORGANIZATION AFTER PRENATAL METHYLAZOXYMETHANOL - A COMBINED IMMUNOCYTOCHEMICAL AND BROMO-DEOXY-URIDINE BIRTHDATING STUDY
Am. Snyderkeller, THE DEVELOPMENT OF STRIATAL PATCH MATRIX ORGANIZATION AFTER PRENATAL METHYLAZOXYMETHANOL - A COMBINED IMMUNOCYTOCHEMICAL AND BROMO-DEOXY-URIDINE BIRTHDATING STUDY, Neuroscience, 68(3), 1995, pp. 751-763
The antimitotic drug methylazoxymethanol was used to destroy striatal
patch neurons during their three-day-period of neurogenesis in the rat
. Single or multiple injections of methylazoxymethanol were given duri
ng embryonic days 13-15, the period when patch neurons are known to un
dergo their final cell division. Methylazoxymethanol treatments produc
ed a dramatic reduction in striatal volume. Immunocytochemical analysi
s revealed the continued presence of patches of neurons that were subs
tance P-immunoreactive and devoid of calbindin and enkephalin immunore
activity. Both the number of patches and relative Volume occupied by p
atches was reduced in methylazoxymelhanol-treated striata. Patch neuro
ns could also be labelled by an intrastriatal injection of FluoroGold
during the first postnatal week. The early ingrowth of nigrostriatal d
opamine afferents was less noticeably patchy in the methylazoxymethano
l-treated animals, in part owing to an overall increase in density. La
rge reductions in the number of neurons immunoreactive for choline ace
tyltransferase were observed, whereas NADPH diaphorase-stained neurons
were not reduced unless methylazoxymethanol was given on embryonic da
y 15, Injections of bromo-deoxy-uridine, either during or after the 24
h that each methylazoxymethanol injection was considered to be effect
ive, revealed that (i) some patch neurons continued to be generated in
the 24-h period following methylazoxymethanol administration, and (ii
) many patch neurons were generated after the effects of methylazoxyme
thanol had worn off.These findings demonstrate that it was impossible
to completely eliminate the patches using methylazoxymethanol injectio
ns during the period of patch neurogenesis. However, methylazoxymethan
ol treatment during this time did produce a dramatic loss of cells and
a relatively greater reduction in patch volume. Despite this disrupti
on, the appropriate compartmentalization of neuroactive substances app
eared to be maintained.