title: Cyclic AMP pathway modifies memory through neural cell adhesion molecule alterations in the rat hippocampus.
abstract: Neural Cell Adhesion Molecules (NCAMs) are known to influence memory by affecting neural cell-cell and cell-extracellular matrix junctions. This study investigated the possible role of cAMP pathway in the expression of hippocampal NCAM and its polysialylated derivative (PSA-NCAM). The following pharmacological tools were employed for manipulation of cAMP pathway: a) forskolin; the activator of adenylyl cyclase (AC), b) 8-Br-cAMP; a protein kinase A (PKA) agonist, c) 8-pCPT-2'-O-Me-cAMP; a selective enhancer of exchange protein activated by cAMP (Epac) and d) Rp-cAMP; a PKA inhibitor. Memory acquisition was tested by passive avoidance paradigm after injecting the above compounds for three consecutive days into the CA1 region of dorsal hippocampus of rats. Forskolin and 8-Br-cAMP enhanced memory retrieval while Rp-cAMP significantly reduced memory and NCAM levels. 8-pCPT-2'-O-Me-cAMP failed to alter memory performance or NCAM levels as compared to vehicle. We observed no significant changes in PSA-NCAM, however the expression of St8sia4 and St8sia2 (the polysialyltransferase isoforms) were altered. The mRNA levels of St8sia4 was down-regulated by 8-Br-cAMP, Rp-cAMP and 8-pCPT while forskolin led to almost 3 and 5 fold increase in mRNAs of St8sia2 and St8sia4, respectively. The current insight might endorse the predominant role of PKA as compared to Epac in cAMP pathway in expression of NCAM and memory function.
authors.affiliation: Tehran University of Medical Sciences arazmi@razi.tums.ac.ir.
authors.forename: Ali
authors.initials: A
authors.lastname: Razmi
authors.affiliation: Tehran University of Medical Sciences sahebgha@tums.ac.ir.
authors.forename: Mousa
authors.initials: M
authors.lastname: Sahebgharani
authors.affiliation: Tehran University of Medical Sciences m.h.khanni@gmail.com.
authors.forename: Mohammad Hossein
authors.initials: MH
authors.lastname: Khani
authors.affiliation: Damghan University, Damghan hpaylakhi@gmail.com.
authors.forename: Seyed Hassan
authors.initials: SH
authors.lastname: Paylakhi
authors.affiliation: Shahid Beheshti University of Medical Sciences, Tehran faizi64@yahoo.com.
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Faizi
authors.affiliation: Tehran University of Medical Sciences zarinmr@ams.ac.ir.
authors.forename: Mohammad-Reza
authors.initials: MR
authors.lastname: Zarrindast
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D015151:Immunoblotting; D008297:Male; D008568:Memory / Q000187:drug effects*; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D012794:Sialic Acids / Q000378:metabolism; D013873:Thionucleotides / Q000494:pharmacology
chemical_list: C473217:8-(4-chloro-phenylthio)-2'-O-methyladenosine-3'-5'-cyclic monophosphate; D039842:Neural Cell Adhesion Molecule L1; D019006:Neural Cell Adhesion Molecules; D012794:Sialic Acids; D013873:Thionucleotides; C103469:polysialyl neural cell adhesion molecule; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; C016957:adenosine-3',5'-cyclic phosphorothioate; D000242:Cyclic AMP