Changes in AMPA glutamate and dopamine D2 receptors in hypoxic-ischemic basal ganglia necrosis.
Changes in the AMPA glutamate receptor subunits (GluR1, 2-3, and 4) and dopamine D2 receptor (D2R) were investigated in 16 cases of hypoxic-ischemic basal ganglia necrosis (BGN) by immunohistochemistry. Immunoreactivity to GluR1, 2-3, and 4 was observed in the cytoplasm and dendrites of small and large neurons in the basal ganglia. Neuronal immunoreactivity to GluR1, 2-3, and 4 was decreased in cases with acute BGN as compared with that in age-matched controls, the areas of decreased immunoreactivity corresponding to the damaged regions observed on hematoxylin and eosin staining. Glia in the basal ganglia exhibited immunoreactivity to GluR4 in 4 patients with acute BGN, 3 of the 4 surviving for 12 to 35 days. In addition, neuronal immunoreactivity to D2R was also decreased in cases of acute BGN, the decrease being similar to that of GluR1, 2-3, and 4. Our results suggest that excitotoxicity mediated by GluR1, 2-3, and 4 is involved in the pathogenesis of hypoxic-ischemic neuronal damage, and that GluR4 expressed in glia of the BG in the late stage of hypoxic-ischemic injury may participate in the delayed and long-term response of the glia to injury. The decrease in neuronal D2R may be related to downregulated synthesis of the D2R protein induced by the decrease in GluR1-4 in the basal ganglia.
Meng
S Z
SZ
Department of Mental Retardation and Birth Defect Research; National Institute of Neuroscience; National Center of Neurology and Psychiatry; Tokyo, Japan.
Ohyu
J
J
Takashima
S
S
D001238:Asphyxia Neonatorum / Q000473:pathology*; D001479:Basal Ganglia / Q000098:blood supply* / Q000473:pathology; D001925:Brain Damage, Chronic / Q000473:pathology; D002545:Brain Ischemia / Q000473:pathology*; D003342:Corpus Striatum / Q000473:pathology; D003593:Cytoplasm / Q000473:pathology; D003712:Dendrites / Q000473:pathology; D005260:Female; D005311:Fetal Hypoxia / Q000473:pathology*; D005865:Gestational Age; D006801:Humans; D002534:Hypoxia, Brain / Q000473:pathology*; D007231:Infant, Newborn; D008297:Male; D009336:Necrosis; D009457:Neuroglia / Q000473:pathology; D009474:Neurons / Q000473:pathology; D011247:Pregnancy; D018091:Receptors, AMPA / Q000032:analysis*; D017448:Receptors, Dopamine D2 / Q000032:analysis*; D017470:Receptors, Glutamate / Q000032:analysis*
D018091:Receptors, AMPA; D017448:Receptors, Dopamine D2; D017470:Receptors, Glutamate