Melatonin induces tyrosine hydroxylase mRNA expression in the ventral mesencephalon but not in the hypothalamus.
We have evaluated the effect of chronic administration of melatonin in terms of mRNA expression for tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis, and in the terms of dopamine (DA) transporter (DAT) by means of in situ hybridization. Experimental rats received daily late afternoon injections of 1.5 mg/kg melatonin for 30 days and analysis were performed in the ventral mesencephalon including the substantia nigra (SN) and ventral tegmental area (VTA), and hypothalamus. In the ventral mesencephalon, melatonin treatment significantly induced TH mRNA levels in individual dopaminergic neurons in SN and VTA. In contrast, DAT mRNA levels remained at control levels. Striatal synaptosomal DA uptake was not modified by melatonin treatment as compared with controls. Analysis of glutamic acid decarboxylase (GAD) mRNA in SN, the biosynthetic enzyme for GABAergic neurons, revealed no effect of melatonin treatment on mRNA levels for this marker. In the hypothalamus, we performed mRNA quantitation for TH in arcuate nucleus (Arc) and supraoptic nucleus (SO). Melatonin treatment failed to alter mRNA levels in either area. We detected weak but significant mRNA levels for DAT in Arc, SO, zona incerta (ZI) and periventricular hypothalamic nucleus (Pe). However, because of the low levels of mRNA in hypothalamic areas we were unable to perform a reliable measurement of DAT mRNA levels in response to melatonin treatment. We conclude that melatonin administration, that combines antioxidant capacity and a tissue-specific TH inducing effect, may be useful as a pharmacological agent to protect dopaminergic neurons from degeneration.
Venero
José L
JL
Departamento de Bioquímica, Bromatología, Toxicología y Medicina Legal, Facultad de Farmacia, Universidad de Sevilla, Sevilla, Spain.
Absi
El-Hadi
el-H
Cano
Josefina
J
Machado
Alberto
A
D000818:Animals; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D005968:Glutamate Decarboxylase / Q000235:genetics; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism*; D017403:In Situ Hybridization; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000235:genetics; D008636:Mesencephalon / Q000187:drug effects* / Q000378:metabolism*; D009410:Nerve Degeneration / Q000517:prevention & control; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D014018:Tissue Distribution; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics*
D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C493216:Slc6a3 protein, rat; D014446:Tyrosine 3-Monooxygenase; D005968:Glutamate Decarboxylase; D008550:Melatonin; D004298:Dopamine