3-Hydroxyanthranilic acid oxygenase-containing astrocytic processes surround glutamate-containing axon terminals in the rat striatum

Abstract

Glutamate, the major transmitter of the corticostriatal pathway, is present in abundance in the striatum. 3-Hydroxyanthranilic acid oxygenase (3HAO) is the biosynthetic enzyme for quinolinic acid, an endogenous agonist of the NMDA glutamate receptor subtype and a potent neurotoxin. In order to explore the anatomical basis of possible functional interactions between glutamate and quinolinic acid in the rat striatum, pre- and postembedding immunocytochemical methods were used to localize 3HAO immunoreactivity (-i) and glutamate-i at the electron microscopic level. In accordance with previous light microscopic and biochemical studies, 3HAO-i was detected exclusively in astrocytes throughout the striatum. Notably, 3HAO-i was present in fine- caliber glial processes that often surrounded or abutted synaptic profiles, both asymmetric and symmetric. Glutamate-i was heavily deposited (3–13-fold higher gold particle density than tissue average) in axon terminals forming asymmetric synapses with spines and, occasionally, dendrites. In contrast, terminals forming symmetric synapses, dendrites, neuronal somata, and glial cells contained significantly less labeling than terminals forming asymmetric synapses. In double-labeled material, 3HAO-i was observed in glial processes that partially surrounded or were adjacent to glutamate-labeled terminals forming asymmetric synapses. 3HAO-labeled glial processes were also adjacent to unlabeled terminals forming symmetric synapses. Since quinolinic acid is known to enter the extracellular compartment readily, these results suggest that astrocytic quinolinic acid may participate in the regulation of glutamatergic neurotransmission in the rat striatum.

Ultrastructural localization of reelin in the cortex in post-mortem human brain

“…Figure 5A in Rodriguez et al (2000) shows in the nonhuman primate, Erythrocebus pata, a small irregularly shaped reelin-labeled process remarkably similar in morphology to that of an astroglial process (Roberts et al, 1995), although the profile was interpreted by the authors to be a dendritic spine. Thus, the presence and extent of reelin labeling in glial cells in nonhuman primates is somewhat unclear, and, if reelin labeling present, it is probably less abundant than in human.…”

“…Reelin levels are decreased in several brain regions in schizophrenia, bipolar disease, depression (Alcantara et al, 1998;Impagnatiello et al, 1998;Fatemi et al, 2000;Guidotti et al, 2000), autism (Persico et al, 2001;Reichelt et al, 2001), and lissencephaly (Hong et al, 2000). The replicated decrease in reelin mRNA in schizophrenia (Impagnatiello et al, 1998;Guidotti et al, 2000) is particularly interesting considering the evidence from post-mortem studies that schizophrenia is associated with impaired cell migration in the neocortex (Akbarian et al, 1996;Kirkpatrick et al, 1999Kirkpatrick et al, , 2003 and the possibility that reelin is related to dendritic spine (Roberts et al, 1995;Glantz and Lewis, 2000) and migration (Eastwood and Harrison, 2003) abnormalities in this disorder. Moreover, reeler heterozygotes share with schizophrenic subjects anatomical and behavioral deficits, such as decreased cerebral reelin levels, and abnormal responses to prepulse inhibition and reactions in an elevated plus maze (Impagnatiello et al, 1998;Tueting et al, 1999;Guidotti et al, 2000;Ballmaier et al, 2002).…”

Quinolinic Acid: An Endogenous Neurotoxin with Multiple Targets

“…This intermediate compound can also produce picolinic acid instead of QUIN [7]. 3-HAO is an iron dependent enzyme requiring Fe 2+ ions and sulfhydryl groups for its activity and is presented in the mitochondrial membrane [8] and in the excitatory synapses [9]. Finally, QUIN is catabolized to NAD + and carbon dioxide by the action of quinolinate phosphoribosyl transferase (QPRT).…”

Immuno-electron microscopy reveals that the excitotoxin quinolinate is associated with the plasma membrane in human peripheral blood monocytes/macrophages

“…The simplest interpretation is that the QUIN biosynthetic enzyme, 3-hydroxyanthranilic acid oxygenase (3-HAO), is localized near the inner side of the plasma membrane. However, a recent study has shown that in astrocytes, 3-HAO is distributed throughout the cytoplasm and perhaps also in the nucleus (Roberts et al 1995). If this turns out to be the case in the Mé, perhaps mechanisms involving binding proteins may exist to concntrate QUIN near the periphery of the cell and then release it.…”