title: Selective enhancement of wnt4 expression by cyclic AMP-associated cooperation between rat central astrocytes and microglia.
abstract: The wnt protein family has important members involved in cell differentiation, proliferation and plasticity expression; however, little is known about its biosynthesis processes. On the other hand, an increase in the intracerebral cyclic adenosine 3', 5'-monophosphate (cAMP) level leads to synaptic plasticity via the de novo synthesis of any protein. Here, the effect of dibutyryl cAMP (dbcAMP), a membrane permeability cAMP analog, on the wnt family was investigated in rat primary-cultured glial cells containing astrocytes and microglia. Among wnt3a, 4, 5a, 7a and 11 mRNA, only wnt4 expression was increased by longer treatment (24 h), compared with short treatment (2 h), with dbcAMP in a concentration-dependent manner, and its effect reached statistical significance at 1 mM. In cultures of isolated astrocytes or microglia, wnt4 expression was not affected by 1 mM dbcAMP for 24 h, and microglial wnt4 protein was undetectable even when cells were treated with the drug. Mixed glial cells treated for 24 h with 1 mM dbcAMP showed significantly increased wnt4 protein, as well as mRNA. Immunofluorescence manifested that cells that expressed wnt4 protein were astrocytes, but not microglia. Intraperitoneal injection of 1.25 mg/kg rolipram, a phosphodiesterase (PDE) IV inhibitor that can pass through the blood brain barrier and inhibits cAMP degradation specifically, showed a tendency to increase wnt4 expression in the adult rat brain after 24 h, and the increases in wnt4 mRNA and protein levels reached statistical significance in the hippocampus and striatum, respectively. This is the first finding to help elucidate the selective biosynthesis of central wnt4 through cAMP-stimulated microglia and astrocytes interaction.
authors.affiliation: Department of Pharmacotherapeutics, Graduate School of Pharmacy and Pharmaceutical Sciences, Fukuyama University, 985-1 Sanzo, Higashimura-cho, Fukuyama, Hiroshima, 729-0292, Japan; Department of Pharmacotherapeutics, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, 985-1 Sanzo, Higashimura-cho, Fukuyama, Hiroshima, 729-0292, Japan. Electronic address: ohnishi@fupharm.fukuyama-u.ac.jp.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Ohnishi
authors.affiliation: Department of Pharmacotherapeutics, Graduate School of Pharmacy and Pharmaceutical Sciences, Fukuyama University, 985-1 Sanzo, Higashimura-cho, Fukuyama, Hiroshima, 729-0292, Japan.
authors.forename: Tomoka
authors.initials: T
authors.lastname: Urasaki
authors.affiliation: Department of Pharmacotherapeutics, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, 985-1 Sanzo, Higashimura-cho, Fukuyama, Hiroshima, 729-0292, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ochiai
authors.affiliation: Department of Pharmacotherapeutics, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, 985-1 Sanzo, Higashimura-cho, Fukuyama, Hiroshima, 729-0292, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Matsuoka
authors.affiliation: Department of Pharmacotherapeutics, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, 985-1 Sanzo, Higashimura-cho, Fukuyama, Hiroshima, 729-0292, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Takeo
authors.affiliation: Department of Pharmacotherapeutics, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, 985-1 Sanzo, Higashimura-cho, Fukuyama, Hiroshima, 729-0292, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Harada
authors.affiliation: Department of Pharmacotherapeutics, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, 985-1 Sanzo, Higashimura-cho, Fukuyama, Hiroshima, 729-0292, Japan.
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Ohsugi
authors.affiliation: Department of Pharmacotherapeutics, Graduate School of Pharmacy and Pharmaceutical Sciences, Fukuyama University, 985-1 Sanzo, Higashimura-cho, Fukuyama, Hiroshima, 729-0292, Japan; Department of Pharmacotherapeutics, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, 985-1 Sanzo, Higashimura-cho, Fukuyama, Hiroshima, 729-0292, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Inoue
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D003994:Bucladesine / Q000378:metabolism / Q000494:pharmacology*; D002450:Cell Communication / Q000187:drug effects; D018920:Coculture Techniques; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007274:Injections, Intraperitoneal; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D058988:Phosphodiesterase 4 Inhibitors / Q000494:pharmacology; D061251:Primary Cell Culture; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D020889:Rolipram / Q000494:pharmacology; D015398:Signal Transduction; D060528:Wnt4 Protein / Q000819:agonists* / Q000235:genetics / Q000378:metabolism
chemical_list: D058988:Phosphodiesterase 4 Inhibitors; D060528:Wnt4 Protein; C555583:Wnt4 protein, rat; D003994:Bucladesine; D000242:Cyclic AMP; D020889:Rolipram
keywords: Astrocyte; Microglia; Wnt4; cAMP