Glutamatergic regulation of long-term grafts of fetal lateral ganglionic eminence in a rat model of Huntington's disease.
Transplanting fetal striatal tissue is currently considered to be an important alternative strategy in the treatment of Huntington's disease. Although grafted striatal tissue differentiates and shows certain structural and neurochemical features of the normal striatum and receives host afferents, it is not clear whether host-derived afferent inputs can modulate the activity of neurotransmitter receptors and their signaling in the graft. An intricate interaction between dopaminergic and glutamatergic systems is pivotal for striatal function. In the present study, the modulation of D(2) receptors in the graft by host-derived glutamatergic afferents via NMDA receptors was investigated using haloperidol-induced c-Fos expression. The results indicate that haloperidol induces c-Fos in a large number of neurons in the P-zones of the graft and this induction is significantly suppressed by pretreatment with the NMDA receptor antagonist, MK-801. Therefore, the NMDA receptor-mediated modulation of D(2) receptor function seen in the normal striatum is established in the striatostriatal grafts.
Hussain
N
N
Department of Anatomy and Cell Biology, The University of Western Ontario, London, ON, Canada N6A 5C1.
Flumerfelt
B A
BA
Rajakumar
N
N
D000818:Animals; D001930:Brain Injuries / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D016380:Brain Tissue Transplantation; D003342:Corpus Striatum / Q000196:embryology / Q000637:transplantation*; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D016332:Fetal Tissue Transplantation; D005455:Fluorescent Antibody Technique; D005973:Glutamine / Q000378:metabolism*; D006220:Haloperidol / Q000494:pharmacology; D006816:Huntington Disease / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000378:metabolism; D017378:Quinolinic Acid / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
D018492:Dopamine Antagonists; D018691:Excitatory Amino Acid Antagonists; D016760:Proto-Oncogene Proteins c-fos; D017448:Receptors, Dopamine D2; D016194:Receptors, N-Methyl-D-Aspartate; D005973:Glutamine; D016291:Dizocilpine Maleate; D017378:Quinolinic Acid; D006220:Haloperidol