Differential expression and distribution of alpha-, beta-, and gamma-synuclein in the developing human substantia nigra.
Although the functions of alpha-, beta-, and gamma-synuclein (alphaS, betaS, gammaS, respectively) are unknown, these synaptic proteins are implicated in the pathogenesis of Parkinson's disease (PD) and related disorders. For example, alphaS forms Lewy bodies (LBs) in substantia nigra (SN) neurons of PD. However, since it is not known how these hallmark PD lesions contribute to the degeneration of SN neurons or what the normal function of alphaS is in SN neurons, we studied the developing human SN from 11 weeks gestational age (GA) to 16 years of age using immunohistochemistry and antibodies to alphaS, betaS, gammaS, other synaptic proteins, and tyrosine hydoxylase (TH). SN neurons expressed TH at 11 weeks GA and alphaS, betaS, and gammaS appeared initially at 15, 17, and 18 weeks GA, respectively. These synucleins first appeared in perikarya of SN neurons after synaptophysin, but about the same time as synaptotagmin and synaptobrevin. Redistribution of alphaS from perikarya to processes of SN neurons occurred by 18 weeks GA in parallel with synaptophysin, while betaS and synaptotagmin were redistributed similarly between 20 and 28 weeks GA and this also occurred with gammaS and synaptobrevin between 33 weeks GA and 9 months postnatal. These data suggest that alphaS, betaS, and gammaS may play a functional role in the development and maturation of SN neurons, but it remains to be determined how sequestration of alphaS as LBs in PD contributes to the degeneration of SN neurons.
Alzheimer's Disease Research Center, Washington University School of Medicine, St Louis, Missouri 63110, USA.
J E
JE
Galvin
T M
TM
Schuck
V M
VM
Lee
J Q
JQ
Trojanowski
D000293:Adolescent; D002135:Calcium-Binding Proteins; D002675:Child, Preschool; D005260:Female; D005333:Fetus / Q000196:embryology / Q000378:metabolism*; D018260:Gelsolin; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011247:Pregnancy; D013378:Substantia Nigra / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D050857:Synaptotagmins; D051843:Synucleins; D051845:gamma-Synuclein
D002135:Calcium-Binding Proteins; D018260:Gelsolin; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D051843:Synucleins; C016953:brevin; D051845:gamma-Synuclein; D050857:Synaptotagmins