Immunohistochemical localization of PDE10A in the rat brain.
PDE10A is a newly identified cAMP/cGMP phosphodiesterase for which mRNA is highly expressed in the mammalian striatum. In the present study, PDE10A protein and mRNA expression throughout the rat brain were determined, using a monoclonal antibody (24F3.F11) for Western blot and immunohistochemical analyses and an antisense riboprobe for in situ hybridization. High levels of mRNA are observed in most of the neuronal cell bodies of striatal complex (caudate n, n. accumbens and olfactory tubercle), indicating that PDE10A is expressed by the striatal medium spiny neurons. PDE10A-like immunoreactivity is dense throughout the striatal neuropil, as well as in the internal capsule, globus pallidus, and substantia nigra. These latter regions lack significant expression of PDE10A mRNA. Thus, PDE10A is transported throughout the dendritic tree and down the axons to the terminals of the medium spiny neurons. These data suggest a role for PDE10A in regulating activity within both the striatonigral and striatopallidal pathways. In addition, PDE10A immunoreactivity and mRNA are found at lower levels in the hippocampal pyramidal cell layer, dentate granule cell layer and throughout the cortex and cerebellar granule cell layer. Immunoreactivity is detected only in cell bodies in these latter regions. This more restricted subcellular localization of PDE10A outside the striatum suggests a second, distinct function for the enzyme in these regions.
Seeger
Thomas F
TF
CNS Discovery, Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA.
Bartlett
Brenda
B
Coskran
Timothy M
TM
Culp
Jeffrey S
JS
James
Larry C
LC
Krull
David L
DL
Lanfear
Jerry
J
Ryan
Anne M
AM
Schmidt
Christopher J
CJ
Strick
Christine A
CA
Varghese
Alison H
AH
Williams
Robert D
RD
Wylie
Patricia G
PG
Menniti
Frank S
FS
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001345:Autoradiography; D015153:Blotting, Western; D001921:Brain / Q000166:cytology* / Q000378:metabolism*; D001923:Brain Chemistry; D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization; D007313:Insecta; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D020319:Oligodeoxyribonucleotides, Antisense; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D010759:Phosphorus Isotopes / Q000493:pharmacokinetics; D011233:Precipitin Tests; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
D000911:Antibodies, Monoclonal; C493957:Cdkn1a protein, mouse; C493958:Cdkn1a protein, rat; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D018076:DNA, Complementary; D020319:Oligodeoxyribonucleotides, Antisense; D010446:Peptide Fragments; D010759:Phosphorus Isotopes; D012333:RNA, Messenger; C492284:Pde10a protein, mouse; D010727:Phosphoric Diester Hydrolases