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.
Laboratory of Molecular Neurobiology, Cornell University Medical College, Burke Medical Research Institute, White Plains, NY 10605.
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Park
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Stone
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Baker
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Wessel
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Kim
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Towle
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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