Developmental expression of calmodulin-dependent cyclic nucleotide phosphodiesterase in rat brain.
The patterns of expression of calmodulin-dependent cyclic nucleotide phosphodiesterase (CaM-PDE) have been studied in developing and adult rat brain using affinity-purified polyclonal antibodies against CaM-PDE. An immunocytochemical map of adult brain regions expressing CaM-PDE, constructed from serial coronal brain sections, illustrated that CaM-PDE was expressed in specific neuronal subpopulations throughout the adult rat brain. Immunoblot analysis coupled with subcellular fractionation indicated that CaM-PDE was primarily localized to cytoplasmic fractions, with a small amount associated with synaptosomal membranes. Immunoblots from developing brain indicated that CaM-PDE expression increased dramatically during postnatal days 7-20 (PND 7-20); parallel increases in CaM-PDE enzyme activity occurred during this same time. Immunocytochemical studies indicated that several distinct patterns of CaM-PDE expression occurred during development. Neocortex showed low levels of CaM-PDE immunoreactivity in neuronal somata of layers III, V and VI on PND 4 that increased by PND 11; the adult somatodendritic pattern of immunoreactivity was observed by PND 60. Similar patterns were observed in cerebellar Purkinje cells, with somatodendritic staining observed by PND 12. By contrast, caudate-putamen, the inferior olive and the hypoglossal nuclei expressed high levels of CaM-PDE on PND 4, with levels considerably lower in the adult animal. The different patterns of expression suggest that in neocortex and cerebellum, CaM-PDE increases during the period of neuronal differentiation and active synaptogenesis, while in the caudate-putamen, inferior olive and hypoglossal nucleus, high levels may be required early in development.
Billingsley
M L
ML
Department of Pharmacology, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.
Polli
J W
JW
Balaban
C D
CD
Kincaid
R L
RL
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000196:embryology / Q000201:enzymology* / Q000254:growth & development; D002147:Calmodulin / Q000378:metabolism*; D005314:Embryonic and Fetal Development; D007150:Immunohistochemistry; D051381:Rats; D011919:Rats, Inbred Strains
D002147:Calmodulin