Developmental and age-related changes of dopamine transporter, and dopamine D1 and D2 receptors in human basal ganglia.
The developmental and age-related changes of the dopamine transporter (DAT), and the dopamine D1 and D2 receptor (D1R and D2R) subtypes were investigated in basal ganglia (BG) of human brain. DAT immunostaining was mainly observed in the neuropil, neurons, and glia of the striatum. The DAT-positive neuropil was detectable at 32 GW, a peak being reached at 9-10 years of age, with a decrease to 50-63 years of age. The developmental pattern of DAT immunoreactivity in neuron was similar to that of the neuropil. DAT-positive glia were observed in the BG at 32 GW, which increased slightly at 38-40 GW, and then did not obviously change until 6-8 months after birth. D2R-positive neurons were clearly observed at 19 GW, a peak being reached at 32 GW and 1-3 months of age in the globus pallidus and striatum, respectively, with a decrease after 9-10 years of age. D1R was expressed as early as D2R, but decreased after 6-8 months. Our results suggest that D1R and D2R expression is an intrinsic property of striatal neurons and is independent of dopaminergic innervation. D1R may play a more important role in neuronal maturation of the BG than D2R. D2R may be closely correlated with late neuronal development. The higher expression of DAT during adolescence may be related to function of the BG which learns complex behavioral patterns. The significance of the age-related decreases in DAT, D1R and D2R in the BG remains to be further investigated.
Meng
S Z
SZ
Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo, Japan.
Ozawa
Y
Y
Itoh
M
M
Takashima
S
S
D000293:Adolescent; D000328:Adult; D000375:Aging / Q000378:metabolism*; D001479:Basal Ganglia / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D050483:Dopamine Plasma Membrane Transport Proteins; D005314:Embryonic and Fetal Development; D005260:Female; D005865:Gestational Age; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C493214:SLC6A3 protein, human