Midbrain dopamine neurons regulate preprotachykinin-A mRNA expression in the rat forebrain during development.
Intracerebroventricular 6-hydroxydopamine injections were performed at postnatal days 3 and 6 in animals pretreated with the norepinephrine uptakeblocker desimipramine in order to generate a selective lesion of dopamine neurons. In situ hybridization was then used to analyze preprotachykinin-A (PPT-A) mRNA expression in the lesioned as well as in saline-injected control animals. The midbrain dopaminergic lesion caused a 22-25% increase in the level of PPT-A mRNA in cingulate cortex and frontoparietal cortex when analysed at 2 weeks of age, compared to saline-injected control animals. In contrast, the lesion caused no change in PPT-A mRNA expression in the neonatal caudate-putamen. These results indicate that dopamine neurons downregulate the expression of PPT-A mRNA specifically in cingulate cortex and frontoparietal cortex during early postnatal brain development. In the adult rat forebrain, lesioned at P3 and P6, no change in the level of PPT-A mRNA was seen in cingulate cortex and frontoparietal cortex. However, a 29% decrease in PPT-A mRNA was seen in the lateral caudate-putamen with no significant change in neurons of medial caudate-putamen. Thus, dopamine neurons appears to exert a region specific influence on PPT-A mRNA expression during brain development.
Brené
S
S
Department of Medical Chemistry, Karolinska Institute, Stockholm, Sweden.
Lindefors
N
N
Persson
H
H
D000818:Animals; D000831:Animals, Newborn; D003714:Denervation; D003891:Desipramine / Q000494:pharmacology; D004298:Dopamine; D005786:Gene Expression Regulation; D008297:Male; D008636:Mesencephalon / Q000166:cytology / Q000254:growth & development / Q000502:physiology*; D016627:Oxidopamine / Q000633:toxicity; D016548:Prosencephalon / Q000254:growth & development / Q000378:metabolism*; D011498:Protein Precursors / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000502:physiology; D015320:Tachykinins / Q000096:biosynthesis*
D011498:Protein Precursors; D012333:RNA, Messenger; D011954:Receptors, Dopamine; D015320:Tachykinins; C044206:preprotachykinin; D016627:Oxidopamine; D003891:Desipramine; D004298:Dopamine