Decreased tyrosine hydroxylase messenger RNA in the surviving dopamine neurons of the substantia nigra in Parkinson's disease: an in situ hybridization study.
Parkinson's disease is associated with a massive loss in melanized dopaminergic neurons in the substantia nigra resulting in a severe striatal dopaminergic denervation. The hyperactivity which develops in the remaining striatal dopaminergic terminals may be related to an increased rate of tyrosine hydroxylation. This could be related to changes in the level of expression of the gene coding for tyrosine hydroxylase. Thus, the detection of tyrosine hydroxylase messenger RNA was looked for at cellular levels by in situ hybridization histochemistry. Image analysis shows that the hybridization signal was significantly reduced in the surviving neurons when compared to control. The subnormal tyrosine hydroxylase messenger RNA content may express a change in level of tyrosine hydroxylase gene transcription, possibly in relation to sustained suffering of the neurons still present at late stages of the disease.
Javoy-Agid
F
F
INSERM U 289, Hôpital de la Salpêtrière, Paris, France.
Hirsch
E C
EC
Dumas
S
S
Duyckaerts
C
C
Mallet
J
J
Agid
Y
Y
D000368:Aged; D000369:Aged, 80 and over; D002470:Cell Survival; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D008636:Mesencephalon / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism*; D009693:Nucleic Acid Hybridization; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism*; D013378:Substantia Nigra / Q000378:metabolism* / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics*
D012333:RNA, Messenger; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine