Cyclic AMP Pathway Modifies Memory Through Neural Cell Adhesion Molecule Alterations in the Rat Hippocampus
-
Ali Razmi
,
Mousa Sahebgharani
,
Mohammad Hossein Khani
,
Seyed Hassan Paylakhi
,
Mehrdad Faizi
,
Mohammad-Reza Zarrindast
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.
Bourtchouladze R, Abel T, Berman N, et al. Different training procedures recruit either one or two critical periods for contextual memory consolidation, each of which requires protein synthesis and PKA. Learn Mem. 1998;5(4-5):365-74.
Barros DM, Izquierdo LA, Mello e Souza T, et al. Molecular signalling pathways in the cerebral cortex are required for retrieval of one-trial avoidance learning in rats. Behav Brain Res 2000;114(1-2):183-92.
Ouyang M, Zhang L, Zhu JJ, et al. Epac signaling is required for hippocampus-dependent memory retrieval. Proc Natl Acad Sci U S A 2008;105(33):11993-7.
Morozov A, Muzzio IA, Bourtchouladze R, et al. Rap1 couples cAMP signaling to a distinct pool of p42/44MAPK regulating excitability, synaptic plasticity, learning, and memory. Neuron 2003;39(2):309-25.
Lopez-Fernandez MA, Montaron MF, Varea E, et al.Upregulation of polysialylated neural cell adhesion molecule in the dorsal hippocampus after contextual fear conditioning is involved in long-term memory formation. J Neurosci 2007;27(17):4552-61.
Markram K, Lopez Fernandez MA, Abrous DN, et al. Amygdala upregulation of NCAM polysialylation induced by auditory fear conditioning is not required for memory formation, but plays a role in fear extinction. Neurobiol Learn Mem 2007;87(4):573-82.
Cambon K, Hansen SM, Venero C, et al. A synthetic neural cell adhesion molecule mimetic peptide promotes synaptogenesis, enhances presynaptic function, and facilitates memory consolidation. J Neurosci 2004;24(17):4197-204.
Doherty P, Williams G, Williams EJ. CAMs and axonal growth: a critical evaluation of the role of calcium and the MAPK cascade. Mol Cell Neurosci 2000;16(4):283-95.
Storms SD, Rutishauser U. A role for polysialic acid in neural cell adhesion molecule heterophilic binding to proteoglycans. J Biol Chem 1998;273(42):27124-9.
Seki T, Arai Y. Distribution and possible roles of the highly polysialylated neural cell adhesion molecule (NCAM-H) in the developing and adult central nervous system. Neurosci Res 1993;17(4):265-90.
Doyle E, Nolan PM, Bell R, et al. Intraventricular infusions of anti-neural cell adhesion molecules in adiscrete posttraining period impair consolidation of a passive avoidance response in the rat. J Neurochem 1992;59(4):1570-3.
Eckhardt M, Bukalo O, Chazal G, et al. Mice deficient in the polysialyltransferase ST8SiaIV/PST-1 allow discrimination of the roles of neural cell adhesion moleculeprotein and polysialic acid in neural development and synaptic plasticity. J Neurosci 2000;20(14):5234-44.
Senkov O, Sun M, Weinhold B, Gerardy-Schahn R, Schachner M, Dityatev A. Polysialylated neural cell adhesion molecule is involved in induction of long-term potentiation and memory acquisition and consolidation in a fear-conditioning paradigm. J Neurosci 2006;26(42):10888-109898.
Bisaz R, Sandi C. The role of NCAM in auditory fear conditioning and its modulation by stress: a focus on the amygdala. Genes Brain Behav 2010;9(4):353-64.
Arami S, Jucker M, Schachner M, et al. The effect ofcontinuous intraventricular infusion of L1 and NCAM antibodies on spatial learning in rats. Behav Brain Res 1996;81(1-2):81-7.
Muller D, Wang C, Skibo G, et al. PSA-NCAM is required for activity-induced synaptic plasticity. Neuron 1996;17:413-22.
Becker CG, Artola A, Gerardy-Schahn R, et al. The polysialic acid modification of the neural cell adhesion molecule is involved in spatial learning and hippocampal long-term potentiation. J Neurosci Res 1996;45(2):143-52.
Price LS, Hajdo-Milasinovic A, Zhao J, et al. Rap1 regulates E-cadherin-mediated cell-cell adhesion. J Biol Chem 2004;279(34):35127-32.
Fukuhara S, Sakurai A, Sano H, et al. Cyclic AMP potentiates vascular endothelial cadherin-mediated cell-cell contact to enhance endothelial barrier function through an Epac-Rap1 signaling pathway. Mol Cell Biol 2005;25(1):136-46.
Kooistra MR, Corada M, Dejana E, et al. Epac1 regulates integrity of endothelial cell junctions through VE-cadherin. FEBS Lett 2005;579(22):4966-72.
Netherton SJ, Sutton JA, Wilson LS, et al. Both protein kinase A and exchange protein activated by cAMP coordinate adhesion of human vascular endothelial cells. Circ Res 2007;101(8):768-76.
Zarrindast MR, Bakhsha A, Rostami P, et al. Effects of intrahippocampal injection of GABAergic drugs on memory retention of passive avoidance learning in rats. J Psychopharmacol 2002;16(4):313-9.
Paxinos G, Watson C, editors. The rat Brain in stereotaxic coordinates. 6th ed. San Diego: Academic Press; 2007.
Rezayof A, Darbandi N, Zarrindast MR. Nicotinic acetylcholine receptors of the ventral tegmental area is involved in mediating morphine-state-dependent learning. Neurobiol Learn Mem 2008;90(1):255-60.
Vogel HG, editor. Drug Discovery and Evaluation: Pharmacological Assays. 3rd ed. Verlag Berlin Heidelberg New York: Springer; 2007.
Markwell MA, Haas SM, Bieber LL, et al. A modification of the Lowry procedure to simplify protein determination in membrane and lipoprotein samples. Anal Biochem 1978;87(1):206-10.
Lowry OH, Rosebrough NJ, Farr AL, et al. Protein measurement with the Folin phenol reagent. J Biol Chem 1951;193(1):265-75.
ambrook J, Fritsch EF, Maniatis T, editors. Molecular Cloning: A Laboratory Manual. 2nd ed. NewYork: Cold Spring Harbor Laboratory Press, 1982.
Pfaffl MW, Horgan GW, Dempfle L. Relative expressionsoftware tool (REST) for group-wise comparison and statistical analysis of relative expression results in realtime PCR. Nucleic Acids Res 2002;30(9):e36.
30. Mackowiak M, Markowicz-Kula K, Fijal K, et al. Acute and repeated administration of cocaine differentially regulates expression of PSA-NCAM-positive neurons inthe rat hippocampus. Brain Res 2005;1055(1-2):149-55.
31. Ma N, Abel T, Hernandez PJ. Exchange protein activated by cAMP enhances long-term memory formation independent of protein kinase A. Learn Mem 2009;16(6):367-70.
Winder DG, Martin KC, Muzzio IA, et al. ERK plays a regulatory role in induction of LTP by theta frequency stimulation and its modulation by beta-adrenergic receptors. Neuron 1999;24(3):715-26.
Nguyen PV, Woo NH. Regulation of hippocampal synaptic plasticity by cyclic AMP-dependent protein kinases. Prog Neurobiol 2003;71(6):401-37.
Murchison CF, Zhang XY, Zhang WP, et al. A distinct role for norepinephrine in memory retrieval. Cell 2004;117(1):131-43.
Venero C, Herrero AI, Touyarot K, et al. Hippocampal upregulation of NCAM expression and polysialylation plays a key role on spatial memory. Eur J Neurosci 2006;23(6):1585-95.
Nolan MF, Malleret G, Dudman JT, et al. A behavioral role for dendritic integration: HCN1 channels constrainspatial memory and plasticity at inputs to distal dendrites of CA1 pyramidal neurons. Cell 2004;119(5):719-32.
Merino JJ, Cordero MI, Sandi C. Regulation of hippocampal cell adhesion molecules NCAM and L1 bycontextual fear conditioning is dependent upon time and stressor intensity. Eur J Neurosci 2000;12(9):3283-90.
Benson DL, Huntley GW. Building and remodeling synapses. Hippocampus 2012;22(5):954-68.
Sytnyk V, Leshchyns'ka I, Delling M, et al. Neural cell adhesion molecule promotes accumulation of TGN organelles at sites of neuron-to-neuron contacts. J Cell Biol 2002;159(4):649-61.
Crawford AT, Desai D, Gokina P, et al. E-cadherin expression in postnatal Schwann cells is regulated by the cAMP-dependent protein kinase a pathway. Glia 2008;56(15):1637-47.
Noble M, Albrechtsen M, Moller C, et al. Glial cells express N-CAM/D2-CAM-like polypeptides in vitro. Nature 1985;316(6030):725-8.
Nybroe O, Albrechtsen M, Dahlin J, et al. Biosynthesis of the neural cell adhesion molecule: characterization of polypeptide C. J Cell Biol 1985;101(6):2310-5.
Guiraudie-Capraz G, Chaillan FA, Truchet B, et al. Increase in polysialyltransferase gene expression followingLTP in adult rat dentate gyrus. Hippocampus 2011;21(11):1180-9.
Phillips GR, Krushel LA, Crossin KL. Developmental expression of two rat sialyltransferases that modify the neural cell adhesion molecule, N-CAM. Brain Res Dev Brain Res 1997;102(2):143-55.
Razmi A, Jahanabadi S, Sahebgharani M, et al. EPACSTX interaction may play a role in neurodevelopment/neurogenesis. Med Hypotheses 2013;81(2):216-8.
27-Velayati AA, Masjedi MR, Farnia P, Tabarsi P. Ghanavi J, Ziazarifi AH, et al. Emergence of new forms of totally drug-resistant tuberculosis bacilli: super extensively drug-resistant tuberculosis or totally drug resistant strains in Iran. Chest. 2009; 136:420-5.
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| Issue | Vol 52, No 4 (2014) | |
| Section | Articles | |
| Keywords | ||
| cAMP Hippocampus Memory Neural cell adhesion molecule Passive avoidance Polysialic acid | ||
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