Decreased kainate receptors in the hippocampus of apolipoprotein D knockout mice.
Apolipoprotein D (ApoD) has many actions critical to maintaining mammalian CNS function. It is therefore significant that levels of ApoD have been shown to be altered in the CNS of subjects with schizophrenia, suggesting a role for ApoD in the pathophysiology of the disorder. There is also a large body of evidence that cortical and hippocampal glutamatergic, serotonergic and cholinergic systems are affected by the pathophysiology of schizophrenia. Thus, we decided to use in vitro radioligand binding and autoradiography to measure levels of ionotropic glutamate, some muscarinic and serotonin 2A receptors in the CNS of ApoD(-/-) and isogenic wild-type mice. These studies revealed a 20% decrease (mean+/-SEM: 104+/-10.2 vs. 130+/-10.4 fmol/mg ETE) in the density of kainate receptors in the CA 2-3 of the ApoD(-/-) mice. In addition there was a global decrease in AMPA receptors (F(1,214)=4.67, p<0.05) and a global increase in muscarinic M2/M4 receptors (F(1,208)=22.77, p<0.0001) in the ApoD(-/-) mice that did not reach significance in any single cytoarchitectural region. We conclude that glutamatergic pathways seem to be particularly affected in ApoD(-/-) mice and this may contribute to the changes in learning and memory, motor tasks and orientation-based tasks observed in these animals, all of which involve glutamatergic neurotransmission.
Boer
Simone
S
The Rebecca L. Cooper Research Laboratories, The Mental Health Research Institute, Australia.
Sanchez
Diego
D
Reinieren
Ivo
I
van den Boom
Tom
T
Udawela
Madhara
M
Scarr
Elizabeth
E
Ganfornina
Maria D
MD
Dean
Brian
B
D000818:Animals; D053399:Apolipoproteins D / Q000172:deficiency; D001345:Autoradiography / Q000379:methods; D016291:Dizocilpine Maleate / Q000378:metabolism / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000378:metabolism / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000378:metabolism / Q000493:pharmacokinetics; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D007650:Ketanserin / Q000378:metabolism / Q000493:pharmacokinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018727:Muscarinic Antagonists / Q000378:metabolism / Q000493:pharmacokinetics; D010890:Pirenzepine / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D011869:Radioligand Assay / Q000379:methods; D011877:Radionuclide Imaging; D018092:Kainic Acid Receptors / Q000378:metabolism*; D014018:Tissue Distribution / Q000187:drug effects; D014316:Tritium / Q000378:metabolism; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000378:metabolism / Q000493:pharmacokinetics
D053399:Apolipoproteins D; D016291:Dizocilpine Maleate; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D007650:Ketanserin; D018727:Muscarinic Antagonists; D010890:Pirenzepine; D018092:Kainic Acid Receptors; D014316:Tritium; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C065959:AFDX 384