Synaptic neurochemistry of human striatum during development: changes in sudden infant death syndrome.
There is evidence of abnormalities in the brain-stem monoamine-containing neurons in infants with sudden infant death syndrome (SIDS). By taking advantage of the rich innervation of the human basal ganglia by monoaminergic afferents from cell bodies in the brainstem, we studied the synaptic chemistry of catecholamine and associated neurons of the putamen obtained postmortem from 14 SIDS infants, eight age-matched control infants, and older control subjects of various ages. We found significantly lower concentrations of dopamine and higher homovanillic acid/DA ratios in samples from SIDS infants compared with age-matched control infants. Noradrenaline and 5-hydroxytryptamine were lower in SIDS compared with control subjects, but the difference did not reach statistical significance. There was no clear evidence that dihydroxyphenylacetic acid and 5-hydroxyindoleacetic acid were altered. Immunoblot analysis of striatal tissue showed that samples from infants with SIDS, which exhibited lower DA, also had lower tyrosine hydroxylase protein. Other transmitter-specific neuronal markers were also assessed, including enzymes associated with cholinergic and GABA-containing neurons. We found significantly decreased choline acetyltransferase activities. However, GABA, glutamate, or somatostatin concentrations or monoamine oxidase activities were unchanged in SIDS. We also noted age-dependent changes in brain weights and some synaptic markers by comparing the age-matched infants with older control subjects. Analysis of variance revealed that homovanillic acid, dihydroxyphenylacetic acid, and monoamine oxidase B activities were increased with age. DA and choline acetyltransferase were also found to be positively correlated in putamen. Our findings suggest developmental changes in some transmitter-specific neurons in SIDS that may result from apneic episodes or chronic hypoxia induced before death.
Kalaria
R N
RN
Department of Neurology, Case Western Reserve University School of Medicine, Cleveland, Ohio.
Fiedler
C
C
Hunsaker
J C
JC
Sparks
D L
DL
D000110:Acetylcholinesterase / Q000378:metabolism; D000375:Aging / Q000502:physiology; D001679:Biogenic Amines / Q000378:metabolism*; D015415:Biomarkers; D002332:Carnitine O-Acetyltransferase / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003342:Corpus Striatum / Q000254:growth & development / Q000378:metabolism*; D005260:Female; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D006801:Humans; D007223:Infant; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D012016:Reference Values; D013004:Somatostatin / Q000378:metabolism; D013398:Sudden Infant Death; D013569:Synapses / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D001679:Biogenic Amines; D015415:Biomarkers; D005971:Glutamates; D007527:Isoenzymes; D018377:Neurotransmitter Agents; D018698:Glutamic Acid; D013004:Somatostatin; D005680:gamma-Aminobutyric Acid; D008995:Monoamine Oxidase; D002795:Choline O-Acetyltransferase; D002332:Carnitine O-Acetyltransferase; D000110:Acetylcholinesterase