Perinatal asphyxia induces region-specific long-term changes in mRNA levels of tyrosine hydroxylase and dopamine D-1 and D-2 receptors in rat brain

To study the effects of neonatal asphyxia on gene expression of the dopamin ergic systems, we determined quantitatively the mRNA levels of tyrosine hyd roxylase, dopamine transporter, dopamine D-1 and D-2 receptors in substanti a nigra/ventral tegmental area, striatum and limbic area. The mRNA levels w ere determined at one and 3 weeks after asphyxia by a quantitative reverse transcription polymerase chain reaction method. Spontaneously and Caesarean section born rats showed similar mRNA levels with the exception of an incr ease of tyrosine hydroxylase mRNA levels in the limbic area of 4-week-old a nimals. Five min of asphyxia did not change the mRNA levels in any region c ompared to that in the spontaneously born rats. Fifteen and twenty min of a sphyxia induced region-specific alterations in mRNA levels. In SN/VTA an in crease of tyrosine hydroxylase mRNA levels in the 1-week-old rats and in st riatum an increase of D-1 and D-2 dopamine receptor mRNA levels in the 3-we ek-old rats were observed. Fifteen min of asphyxia induced a selective incr ease of D-1 and D-2 dopamine receptor mRNA levels in the limbic area of 4-w eek-old rats. These observations indicate that neonatal asphyxia triggers a cascade of gene expressions for tyrosine hydroxylase and D-1 and D-2 dopam ine receptors. In I-week-old rats, the gene expression of tyrosine hydroxyl ase increased in the cell body region substantia nigra/ventral tegmental ar ea. This change map increase the D-1 and D-2 dopamine receptor expression i n the target regions striatum and limbic area during further development. ( C) 2000 Elsevier Science B.V. All rights reserved.