Alterations on phosphodiesterase type 7 and 8 isozyme mRNA expression in Alzheimer's disease brains examined by in situ hybridization.
Phosphodiesterases (PDEs) play a central role in signal transduction by regulating intracellular levels of cyclic AMP (cAMP) and cGMP. It has been suggested that cAMP pathways could be upregulated in Alzheimer's disease. By in situ hybridization histochemistry we have determined the expression pattern of two newly described cAMP-specific phosphodiesterases families, PDE7 and PDE8, in several brain areas in control subjects. The hybridization levels of PDE8A mRNA were very low in all brain areas examined. High PDE7B and PDE8B mRNA signal intensities were found in the hippocampal formation. PDE7A was found to be present in both neuronal and non-neuronal cell populations. When the expression of these isozymes in control brains was compared with that in Alzheimer's disease brains staged according to Braak and Braak (Acta Neuropathol. (Berl.) 82 (1991), 239), we found that PDE8B was the only isozyme showing a significant increase, in cortical areas and parts of the hippocampal formation, at Braak stages III-VI. Our results show that the expression of specific cAMP PDE isoforms is selectively regulated in Alzheimer's disease and associated with the stages of the disease. The availability of animal models of Alzheimer's disease and of new pharmacological tools such as selective PDE inhibitors will allow study of the therapeutic potential of the control of cAMP levels in AD.
Pérez-Torres
S
S
Department of Neurochemistry, IIBB/CSIC (IDIBAPS), c/Rosselló 161, 6, E-08036, Barcelona, Spain.
Cortés
R
R
Tolnay
M
M
Probst
A
A
Palacios
J M
JM
Mengod
G
G
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology* / Q000473:pathology; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D054708:Cyclic Nucleotide Phosphodiesterases, Type 7; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis*
D007527:Isoenzymes; D012333:RNA, Messenger; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054708:Cyclic Nucleotide Phosphodiesterases, Type 7; C517458:PDE7A protein, human; C517463:PDE7B protein, human; C468781:PDE8B protein, human