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

Abstract

To study the effects of neonatal asphyxia on gene expression of the dopaminergic systems, we determined quantitatively the mRNA levels of tyrosine hydroxylase, dopamine transporter, dopamine D 1 and D 2 receptors in substantia nigra/ventral tegmental area, striatum and limbic area. The mRNA levels were determined at one and 4 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 increase of tyrosine hydroxylase mRNA levels in the limbic area of 4-week-old animals. Five min of asphyxia did not change the mRNA levels in any region compared to that in the spontaneously born rats. Fifteen and twenty min of asphyxia induced region-specific alterations in mRNA levels. In SN/VTA an increase of tyrosine hydroxylase mRNA levels in the 1-week-old rats and in striatum an increase of D 1 and D 2 dopamine receptor mRNA levels in the 4-week-old rats were observed. Fifteen min of asphyxia induced a selective increase of D 1 and D 2 dopamine receptor mRNA levels in the limbic area of 4-week-old rats. These observations indicate that neonatal asphyxia triggers a cascade of gene expressions for tyrosine hydroxylase and D 1 and D 2 dopamine receptors. In 1-week-old rats, the gene expression of tyrosine hydroxylase increased in the cell body region substantia nigra/ventral tegmental area. This change may increase the D 1 and D 2 dopamine receptor expression in the target regions striatum and limbic area during further development.