DEVELOPMENT OF STRIATAL DOPAMINERGIC FUNCTION .3. PRENATAL-DEVELOPMENT AND POSTNATAL-DEVELOPMENT OF STRIATAL AND CORTICAL MESSENGER-RNAS FOR THE NEUROTROPHIN RECEPTORS TRKB(TK+) AND TRKC AND THEIR REGULATION BY SYNAPTIC DOPAMINE
Ab. Jung et Jp. Bennett, DEVELOPMENT OF STRIATAL DOPAMINERGIC FUNCTION .3. PRENATAL-DEVELOPMENT AND POSTNATAL-DEVELOPMENT OF STRIATAL AND CORTICAL MESSENGER-RNAS FOR THE NEUROTROPHIN RECEPTORS TRKB(TK+) AND TRKC AND THEIR REGULATION BY SYNAPTIC DOPAMINE, Developmental brain research, 94(2), 1996, pp. 133-143
Known neurotrophins in the nigrostriatal system include brain-derived
neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) which exert biolo
gical effects after high affinity binding to their respective tyrosine
kinase receptors, trkB and trkC. We measured striatal trkB(TK+) and t
rkC mRNAs in rat brain sections with in situ hybridization histochemis
try. Both trkB(TK+) and trkC transcripts were present in the striatal
anlage at embryonic day (E) 14 or 16. Striatal trkB(TK+) mRNA levels i
ncreased to a peak in the late prenatal period and gradually declined
in the postnatal period. In contrast, striatal trkC mRNA levels peaked
on E16, then declined to fairly constant levels. Striatal trkB(TK+) g
ene expression increased from the medial to lateral quadrants througho
ut development, whereas trkC mRNA increased from the lateral to medial
quadrants prenatally but increased from the dorsal to ventral quadran
ts on postnatal days (P) 1 and 3. The distinct spatiotemporal developm
ental profiles of trkB(TK+) and trkC mRNA suggest that their respectiv
e ligands BDNF and NT-4/5, and NT-3, may have specialized functions in
striatal neuronal development. Because neurotransmitters may regulate
neurotrophin function in developing neural systems, we treated rats o
f various ages with the indirect dopamine agonist cocaine and measured
the effects of cocaine treatment on transcription of the trk genes. A
cute 1 h cocaine treatment increased trkB(TK+) and trkC mRNA levels in
the P5 striatum but not in the E15, E20, or adult striatum. The trkB(
TK+) effect was blocked by pretreatment with the D1 receptor antagonis
t, SCH23390, and was not affected by pretreatment with the D2 receptor
antagonist, eticlopride. In contrast, trkC regulation may be mediated
by independent stimulation of D1 and D2 receptors. We hypothesize tha
t the endogenous nigrostriatal neurotransmitter dopamine can modulate
striatal neurotrophin responsiveness and thereby influence striatal ne
uronal development during a defined developmental period.