Differential expression of glutamate receptor subtypes in human brainstem sites involved in perinatal hypoxia-ischemia.
This study delineates the development of N-methyl-D-aspartate (NMDA) and non-NMDA receptor binding in the human brainstem, particularly as it relates to issues of the trophic effects of glutamate, the glutamate-mediated ventilatory response to hypoxia, and regional excitotoxic vulnerability to perinatal hypoxia-ischemia. We used tissue autoradiography to map the development of binding to NMDA, alpha-amino-3-hydroxy-5-methyl-4-isoxazole-proprionate (AMPA), and kainate receptors in brainstem sites involved in the glutamate ventilatory response to hypoxia, as well as recognized sites vulnerable to perinatal hypoxia-ischemia. NMDA receptor/channel binding was virtually undetectable in all regions of the human fetal brainstem at midgestation, an unexpected finding given the trophic role for NMDA receptors in early central nervous system maturation in experimental animals. In contrast, non-NMDA (AMPA and kainate) receptor binding was markedly elevated in multiple nuclei at midgestation. Although NMDA binding increased between midgestation and early infancy to moderately high adult levels, AMPA binding dramatically fell over the same time period to low adult levels. High levels of kainate binding did not change significantly between midgestation and infancy, except for an elevation in the infant compared with fetal inferior olive; after infancy, kainate binding decreased to negligible adult levels. Our data further suggest a differential development of components of the NMDA receptor/channel complex. This baseline information is critical in considering glutaminergic mechanisms in human brainstem development, physiology, and pathology.
Panigrahy
A
A
Department of Neurology, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Rosenberg
P A
PA
Assmann
S
S
Foley
E C
EC
Kinney
H C
HC
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000328:Adult; D000368:Aged; D001933:Brain Stem / Q000254:growth & development* / Q000378:metabolism* / Q000503:physiopathology; D002675:Child, Preschool; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D005998:Glycine / Q000494:pharmacology; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D007223:Infant; D007231:Infant, Newborn; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000494:pharmacology; D010622:Phencyclidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011247:Pregnancy; D018091:Receptors, AMPA / Q000187:drug effects / Q000378:metabolism; D017470:Receptors, Glutamate / Q000145:classification / Q000378:metabolism*; D018009:Receptors, Glycine / Q000187:drug effects / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D017478:Receptors, Phencyclidine / Q000187:drug effects / Q000378:metabolism; D013398:Sudden Infant Death / Q000209:etiology* / Q000473:pathology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D017478:Receptors, Phencyclidine; C069052:CGP 39653; D015763:2-Amino-5-phosphonovalerate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C012058:tenocyclidine; D010622:Phencyclidine; D005998:Glycine