Changes in activity and mRNA for rat tryptophan hydroxylase and aromatic L-amino acid decarboxylase of brain serotonergic cell bodies and terminals following neonatal 5,7-dihydroxytryptamine.
In the present study, we examined time-dependent changes in activity, mRNA and immunoreactivity of the serotonin biosynthetic enzymes, tryptophan hydroxylase (TPH) and aromatic L-amino acid decarboxylase (AADC) in dorsal raphe nucleus (DRN), caudal brainstem and hypothalamus, following intracisternal injection of 5,7-dihydroxytryptamine (5,7-DHT) in neonatal rats. TPH activity in central serotonergic cell bodies and terminals was reduced to 20-30% of control levels at 1-8 weeks after neonatal, low-dose 5,7-DHT injection (24 micrograms free base). In contrast, AADC activity was either not changed or decreased to 40% of control levels, depending on the region. In situ hybridization and immunocytochemical staining indicated that 5,7-DHT caused a marked reduction in TPH and AADC message levels as well as the number of 5-HT and AADC-immunoreactive cells within the DRN as early as 1 week after 5,7-DHT. Even 15 weeks after drug administration recovery did not occur. This apparent neuronal loss was region-specific suggesting that some serotonergic neurons are more resistant to neonatal 5,7-DHT treatment than others. Taken together, these studies indicate that neonatal treatment with 5,7-DHT produces a marked and permanent (up to 15 weeks) reduction in the number of central serotonergic neurons.
Park
D H
DH
Laboratory of Molecular Neurobiology, Cornell University Medical College, Burke Medical Research Institute, White Plains, NY 10605.
Stone
D M
DM
Baker
H
H
Wessel
T C
TC
Kim
K S
KS
Towle
A C
AC
Joh
T H
TH
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000096:biosynthesis*; D001921:Brain / Q000166:cytology / Q000502:physiology*; D001933:Brain Stem / Q000201:enzymology; D005260:Female; D007031:Hypothalamus / Q000201:enzymology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D009411:Nerve Endings / Q000201:enzymology / Q000378:metabolism; D009474:Neurons / Q000201:enzymology / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism*; D011903:Raphe Nuclei / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000502:physiology*; D013997:Time Factors; D014365:Tryptophan Hydroxylase / Q000096:biosynthesis*
D012333:RNA, Messenger; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D014365:Tryptophan Hydroxylase; D001142:Aromatic-L-Amino-Acid Decarboxylases