Synaptic Neurochemistry of Human Striatum During Development: Changes in Sudden Infant Death Syndrome |
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Authors: | R. N. Kalaria&Dagger ,C. Fiedler,J. C. Hunsaker III,&Dagger D. L. Sparks &Dagger |
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Affiliation: | Departments of Neurology;Neurosciences, Case Western Reserve University School of Medicine, Cleveland, Ohio;Sanders-Brown Center on Aging;Departments of Pathology;Departments of Neurology, University of Kentucky Medical Center;Kentucky Medical Examiner Program, Justice Cabinet, Lexington, Kentucky, U.S.A. |
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Abstract: | Abstract: 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 monoam-inergic 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 dihydroxyphe-nylacetic 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. |
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Keywords: | Basal ganglia Choline acetyltransferase Development Dopamine Hypoxia Putamen Sudden infant death syndrome. |
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