Persistent improvement in synaptic and cognitive functions in an Alzheimer mouse model after rolipram treatment
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Evidence suggests that Alzheimer disease (AD) begins as a disorder of synaptic function, caused in part by increased levels of amyloid beta-peptide 1-42 (Abeta42). Both synaptic and cognitive deficits are reproduced in mice double transgenic for amyloid precursor protein (AA substitution K670N,M671L) and presenilin-1 (AA substitution M146V). Here we demonstrate that brief treatment with the phosphodiesterase 4 inhibitor rolipram ameliorates deficits in both long-term potentiation (LTP) and contextual learning in the double-transgenic mice. Most importantly, this beneficial effect can be extended beyond the duration of the administration. One course of long-term systemic treatment with rolipram improves LTP and basal synaptic transmission as well as working, reference, and associative memory deficits for at least 2 months after the end of the treatment. This protective effect is possibly due to stabilization of synaptic circuitry via alterations in gene expression by activation of the cAMP-dependent protein kinase (PKA)/cAMP regulatory element-binding protein (CREB) signaling pathway that make the synapses more resistant to the insult inflicted by Abeta. Thus, agents that enhance the cAMP/PKA/CREB pathway have potential for the treatment of AD and other diseases associated with elevated Abeta42 levels.
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Transgenic mouse AD models manifest a spontaneous age-onset impairment of LTP that presumably is linked to impaired performance in memory tests.
“Tg-mouse AD models manifest a spontaneous age-onset impairment of LTP (Gong et al., 2004) that presumably is linked to impaired performance in memory tests (Arendash et al., 2001).”
From The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease (2011) · cites this paper as Gong et al., 2004
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Cites
A synaptic model of memory: long-term potentiation in the hippocampus
Bliss, T. V. P., & Collingridge, G. L. (1993) · Nature · doi:10.1038/361031a0 · Cited by 11,566 · see citing works
Place navigation impaired in rats with hippocampal lesions
Morris, R. G. M., Garrud, P., Rawlins, J. N. P., & O'Keefe, J. (1982) · Nature · doi:10.1038/297681a0 · Cited by 6,340 · see citing works
Walsh, D. M., Klyubin, I., Fadeeva, J. V., Cullen, W. K., Anwyl, R., Wolfe, M. S., Rowan, M. J., & Selkoe, D. J. (2002) · Nature · doi:10.1038/416535a · Cited by 4,291 · see citing works
Correlative Memory Deficits, Aβ Elevation, and Amyloid Plaques in Transgenic Mice
Hsiao, K., Chapman, P., Nilsen, S., Eckman, C., Harigaya, Y., Younkin, S., Yang, F., & Cole, G. (1996) · Science · doi:10.1126/science.274.5284.99 · Cited by 4,210 · see citing works
Triple-Transgenic Model of Alzheimer’s Disease with Plaques and Tangles
Oddo, S., Caccamo, A., Shepherd, J. D., Murphy, M. P., Golde, T. E., Kayed, R., Metherate, R., Mattson, M. P., Akbari, Y., & LaFerla, F. M. (2003) · Neuron · doi:10.1016/s0896-6273(03)00434-3 · Cited by 4,126 · see citing works
Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning.
Phillips, R. G., & LeDoux, J. E. (1992) · Behavioral Neuroscience · doi:10.1037/0735-7044.106.2.274 · Cited by 3,292 · see citing works
Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning.
Phillips, R. G., & LeDoux, J. E. (1992) · Behavioral Neuroscience · doi:10.1037//0735-7044.106.2.274 · Cited by 3,262 · see citing works
Immunization with amyloid-β attenuates Alzheimer-disease-like pathology in the PDAPP mouse
Schenk, D., Barbour, R., Dunn, W., Gordon, G., Grajeda, H., Guido, T., Hu, K., Huang, J., Johnson-Wood, K., Khan, K., et al. (1999) · Nature · doi:10.1038/22124 · Cited by 3,160 · see citing works
Bourtchuladze, R., Frenguelli, B., Blendy, J., Cioffi, D., Schutz, G., & Silva, A. J. (1994) · Cell · doi:10.1016/0092-8674(94)90400-6 · Cited by 1,800 · see citing works
Aβ peptide vaccination prevents memory loss in an animal model of Alzheimer's disease
Morgan, D., Diamond, D. M., Gottschall, P. E., Ugen, K. E., Dickey, C. A., Hardy, J., Duff, K., Jantzen, P. T., DiCarlo, G., Wilcock, D. M., et al. (2000) · Nature · doi:10.1038/35050116 · Cited by 1,488 · see citing works
Nehlig, A., Daval, J., & Debry, G. (1992) · Brain Research Reviews · doi:10.1016/0165-0173(92)90012-b · Cited by 1,463 · see citing works
Increased amyloid-β42(43) in brains of mice expressing mutant presenilin 1
Duff, K., Eckman, C., Zehr, C., Yu, X., Prada, C.-M., Pérez‐Tur, J., Hutton, M., Buée, L., Harigaya, Y., Yager, D., et al. (1996) · Nature · doi:10.1038/383710a0 · Cited by 1,453 · see citing works
Neuropathology of human Alzheimer disease after immunization with amyloid-β peptide: a case report
Nicoll, J. A. R., Wilkinson, D., Holmes, C., Steart, P., Markham, H., & Weller, R. O. (2003) · Nature Medicine · doi:10.1038/nm840 · Cited by 1,397 · see citing works
ABAD Directly Links Aß to Mitochondrial Toxicity in Alzheimer's Disease
Lustbader, J. W., Cirilli, M., Lin, C., Xu, H. W., Takuma, K., Wang, N., Caspersen, C., Chen, X., Pollak, S., Chaney, M., et al. (2004) · Science · doi:10.1126/science.1091230 · Cited by 1,303 · see citing works
Intraneuronal Aβ42 Accumulation in Human Brain
Gouras, G. K., Tsai, J., Naslund, J., Vincent, B., Edgar, M., Checler, F., Greenfield, J. P., Haroutunian, V., Buxbaum, J. D., Xu, H., et al. (2000) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)64700-1 · Cited by 991 · see citing works
Induction of a dominant negative CREB transgene specifically blocks long-term memory in Drosophila
Yin, J. C. P., Wallach, J. S., Del Vecchio, M., Wilder, E. L., Zhou, H., Quinn, W. G., & Tully, T. (1994) · Cell · doi:10.1016/0092-8674(94)90399-9 · Cited by 959 · see citing works
Immunization reverses memory deficits without reducing brain Aβ burden in Alzheimer's disease model
Dodart, J.-C., Bales, K. R., Gannon, K. S., Greene, S. J., DeMattos, R. B., Mathis, C., DeLong, C. A., Wu, S., Wu, X., Holtzman, D. M., et al. (2002) · Nature Neuroscience · doi:10.1038/nn842 · Cited by 858 · see citing works
Spatial mapping: definitive disruption by hippocampal or medial frontal cortical damage in the rat.
Sutherland, R., Kolb, B., & Whishaw, I. (1982) · Neuroscience Letters · doi:10.1016/0304-3940(82)90032-5 · Cited by 573 · see citing works
Ferrer, I., Boada, M., Guerra, M. L. S., Rey, M. J., & Costa‐Jussà, F. R. (2004) · Brain Pathology · doi:10.1111/j.1750-3639.2004.tb00493.x · Cited by 567 · see citing works
Bach, M. E., Barad, M., Son, H., Zhuo, M., Lü, Y.-F., Shih, R., Mansuy, I. M., Hawkins, R. D., & Kandel, E. R. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.9.5280 · Cited by 561 · see citing works
Vitolo, O. V., Sant'Angelo, A., Costanzo, V., Battaglia, F., Arancio, O., & Shelanski, M. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.172504199 · Cited by 534 · see citing works
Nakagawa, S., Kim, J., Lee, R., Malberg, J. E., Chen, J., Steffen, C., Zhang, Y., Nestler, E. J., & Duman, R. S. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-09-03673.2002 · Cited by 486 · see citing works
The Role of the Extracellular Signal-Regulated Kinase Signaling Pathway in Mood Modulation
Einat, H., Yuan, P., Gould, T. D., Li, J., Du, J., Zhang, L., Manji, H. K., & Chen, G. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-19-07311.2003 · Cited by 475 · see citing works
Barad, M., Bourtchouladze, R., Winder, D. G., Golan, H. M., & Kandel, E. R. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.25.15020 · Cited by 431 · see citing works
Schenk, F., & Morris, R. G. M. (1985) · Experimental Brain Research · doi:10.1007/bf00238949 · Cited by 418 · see citing works
Amyloid β protein (Aβ) deposition: Aβ42(43) precedes Aβ40 in down Syndrome
Iwatsubo, T., Mann, D. M. A., Odaka, A., Suzuki, N., & Ihara, Y. (1995) · Annals of Neurology · doi:10.1002/ana.410370305 · Cited by 380 · see citing works
Progressive age‐related development of Alzheimer‐like pathology in APP/PS1 mice
Trinchese, F., Liu, S., Battaglia, F., Walter, S., Mathews, P. M., & Arancio, O. (2004) · Annals of Neurology · doi:10.1002/ana.20101 · Cited by 369 · see citing works
Targeting the CREB pathway for memory enhancers
Tully, T., Bourtchouladze, R., Scott, R., & Tallman, J. F. (2003) · Nature Reviews Drug Discovery · doi:10.1038/nrd1061 · Cited by 355 · see citing works
Arendash, G. W., King, D. L., Gordon, M. N., Morgan, D., Hatcher, J. M., Hope, C. E., & Diamond, D. M. (2001) · Brain Research · doi:10.1016/s0006-8993(00)03186-3 · Cited by 349 · see citing works
Bourtchouladze, R., Lidge, R., Catapano, R., Stanley, J., Gossweiler, S., Romashko, D., Scott, R., & Tully, T. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1834280100 · Cited by 313 · see citing works
Altered responsiveness to cocaine in rats exposed to methylphenidate during development
Andersen, S. L., Arvanitogiannis, A., Pliakas, A. M., LeBlanc, C., & Carlezon, W. A. (2002) · Nature Neuroscience · doi:10.1038/nn777 · Cited by 259 · see citing works
Neurofibromin regulates G protein–stimulated adenylyl cyclase activity
Tong, J., Hannan, F., Zhu, Y., Bernards, A., & Zhong, Y. (2002) · Nature Neuroscience · doi:10.1038/nn792 · Cited by 249 · see citing works
Block of LTP in rat hippocampus in vivo by β-amyloid precursor protein fragments
Cullen, W. K., Suh, Y., Anwyl, R., & Rowan, M. J. (1997) · Neuroreport · doi:10.1097/00001756-199710200-00006 · Cited by 235 · see citing works
Dysregulation of Protein Kinase A Signaling in the Aged Prefrontal Cortex
Ramos, B. P., Birnbaum, S. G., Lindenmayer, I., Newton, S. S., Duman, R. S., & Arnsten, A. F. T. (2003) · Neuron · doi:10.1016/s0896-6273(03)00694-9 · Cited by 218 · see citing works
Dineley, K. T., Xia, X., Bui, D., Sweatt, J. D., & Zheng, H. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m200164200 · Cited by 212 · see citing works
(1995) · PubMed · Cited by 167 · see citing works
LaFerla, F. M., Troncoso, J. C., Strickland, D. K., Kawas, C. H., & Jay, G. D. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119536 · Cited by 162 · see citing works
Rolipram in Major Depressive Disorder: Results of a Double-Blind Comparative Study with Imipramine
Hebenstreit, G. F., Fellerer, K., Fichte, K., Fischer, G., Geyer, N., Meya, U., Sastre-y-Hernández, M., Schöny, W., Schratzer, M., Soukop, W., et al. (1989) · Pharmacopsychiatry · doi:10.1055/s-2007-1014599 · Cited by 159 · see citing works
Zhang, H. (2000) · Neuropsychopharmacology · doi:10.1016/s0893-133x(00)00108-1 · Cited by 154 · see citing works
Amyloid-β Antibody Treatment Leads to Rapid Normalization of Plaque-Induced Neuritic Alterations
Lombardo, J. A., Stern, E. A., McLellan, M. E., Kajdasz, S. T., Hickey, G. A., Bacskai, B. J., & Hyman, B. T. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-34-10879.2003 · Cited by 149 · see citing works
Molecular Neurobiology of Human Cognition
Weeber, E. J., & Sweatt, J. D. (2002) · Neuron · doi:10.1016/s0896-6273(02)00634-7 · Cited by 145 · see citing works
Zhang, H., Zhao, Y., Huang, Y., Dorairaj, N. R., Chandler, L. J., & O’Donnell, J. M. (2004) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300440 · Cited by 141 · see citing works
Zhang, H., & O’Donnell, J. M. (2000) · Psychopharmacology · doi:10.1007/s002130000414 · Cited by 136 · see citing works
Corcoran, K. A., Lu, Y., Turner, R. S., & Maren, S. (2002) · Learning & Memory · doi:10.1101/lm.51002 · Cited by 135 · see citing works
Imanishi, T., Sawa, A., Ichimaru, Y., Miyashiro, M., Kato, S., Yamamoto, T., & Ueki, S. (1997) · European Journal of Pharmacology · doi:10.1016/s0014-2999(96)00969-7 · Cited by 130 · see citing works
Pharmacology of nootropics and metabolically active compounds in relation to their use in dementia
Nicholson, C. D. (1990) · Psychopharmacology · doi:10.1007/bf02244119 · Cited by 130 · see citing works
Impairments of long-term potentiation in hippocampal slices of β-amyloid-infused rats
Itoh, A., Akaike, T., Sokabe, M., Nitta, A., Iida, R., Olariu, A., Yamada, K., & Nabeshima, T. (1999) · European Journal of Pharmacology · doi:10.1016/s0014-2999(99)00601-9 · Cited by 118 · see citing works
Navakkode, S., Sajikumar, S., & Frey, J. U. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.1796-04.2004 · Cited by 114 · see citing works
Piaz, V. D., & Giovannoni, M. P. (2000) · European Journal of Medicinal Chemistry · doi:10.1016/s0223-5234(00)00179-3 · Cited by 109 · see citing works
The effect of caffeine in animal models of learning and memory
Angelucci, M. E. M., Vital, M. A. B. F., Cesário, C., Zadusky, C. R., Rosalen, P. L., & Cunha, C. D. (1999) · European Journal of Pharmacology · doi:10.1016/s0014-2999(99)00225-3 · Cited by 109 · see citing works
Caffeine reverses the memory disruption induced by intra-nigral MPTP-injection in rats
Gevaerd, M. S., Takahashi, R. N., Silveira, R., & Cunha, C. D. (2001) · Brain Research Bulletin · doi:10.1016/s0361-9230(01)00501-9 · Cited by 104 · see citing works
Kŕause, W., & Kühne, G. (1988) · Xenobiotica · doi:10.3109/00498258809041693 · Cited by 104 · see citing works
Petrone, A., Battaglia, F., Wang, C., Dusa, A., Su, J. D., Zagzag, D., Bianchi, R., Casaccia‐Bonnefil, P., Arancio, O., & Sap, J. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg399 · Cited by 85 · see citing works
Nagakura, A., Niimura, M., & Takeo, S. (2002) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0704629 · Cited by 76 · see citing works
Calpain Inhibitors, a Treatment for Alzheimer's Disease: Position Paper
Battaglia, F., Trinchese, F., Liu, S., Walter, S., Nixon, R. A., & Arancio, O. (2003) · Journal of Molecular Neuroscience · doi:10.1385/jmn:20:3:357 · Cited by 63 · see citing works
Pérez, J., Tardito, D., Mori, S., Racagni, G., Smeraldi, E., & Zanardi, R. (2000) · Bipolar Disorders · doi:10.1034/j.1399-5618.2000.020104.x · Cited by 61 · see citing works
Dragunow, M. (2004) · Frontiers in bioscience · doi:10.2741/1197 · Cited by 40 · see citing works
Effects of caffeine on discrimination learning, consolidation, and learned behavior in mice
Castellano, C. (1976) · Psychopharmacology · doi:10.1007/bf00496858 · Cited by 34 · see citing works
Later Developments: Molecular Keys to Age-Related Memory Impairment
Barad, M. (2003) · Alzheimer Disease & Associated Disorders · doi:10.1097/00002093-200307000-00009 · Cited by 18 · see citing works
Pharmacokinetics of proterguride in rat and cynomolgus monkey
Kŕause, W., & Humpel, M. (1988) · Xenobiotica · doi:10.3109/00498258809055135 · Cited by 9 · see citing works
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- Barad, M., Bourtchouladze, R., Winder, D.G., Golan, H., and Kandel, E. 1998. Rolipram, a type IV-specific phosphodiesterase inhibitor, facilitates the establishment of long-lasting long-term poten- tiation and improves memory. Proc. Natl. Acad. Sci.
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Cooke, S. F. (2006) · Brain · doi:10.1093/brain/awl082 · Cited by 1,195 · see citing works
Exercise-linked FNDC5/irisin rescues synaptic plasticity and memory defects in Alzheimer’s models
Lourenco, M. V., Frozza, R. L., de Freitas, G. B., Zhang, H., Kincheski, G. C., Ribeiro, F. C., Gonçalves, R. A., Clarke, J. R., Beckman, D., Staniszewski, A., et al. (2019) · Nature Medicine · doi:10.1038/s41591-018-0275-4 · Cited by 935 · see citing works
Self-citationLugnier, C. (2005) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2005.07.003 · Cited by 873 · see citing works
Lehnart, S. E., Wehrens, X. H. T., Reiken, S. R., Warrier, S., Belevych, A. E., Harvey, R. D., Richter, W., Jin, S.-L. C., Conti, M., & Marks, A. R. (2005) · Cell · doi:10.1016/j.cell.2005.07.030 · Cited by 518 · see citing works
The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease
Ferreira, S. T., & Klein, W. L. (2011) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2011.08.003 · Cited by 442 · see citing works
Gong, B., Cao, Z., Zheng, P., Vitolo, O. V., Liu, S., Staniszewski, A., Moolman, D. L., Zhang, H., Shelanski, M. L., & Arancio, O. (2006) · Cell · doi:10.1016/j.cell.2006.06.046 · Cited by 424 · see citing works
The role of CREB and BDNF in neurobiology and treatment of Alzheimer's disease
Amidfar, M., de Oliveira, J., Kucharska, E., Budni, J., & Kim, Y. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.118020 · Cited by 413 · see citing works
Phosphodiesterases in the CNS: targets for drug development
Menniti, F. S., Faraci, W. S., & Schmidt, C. J. (2006) · Nature Reviews Drug Discovery · doi:10.1038/nrd2058 · Cited by 391 · see citing works
Ricobaraza, A., Cuadrado-Tejedor, M., Pérez-Mediavilla, A., Frechilla, D., Del Río, J., & García-Osta, A. (2009) · Neuropsychopharmacology · doi:10.1038/npp.2008.229 · Cited by 423 · see citing works
Canas, P. M., Porciúncula, L. O., Cunha, G. M. A., Silva, C. G., Machado, N. J., Oliveira, J. M. A., Oliveira, C. R., & Cunha, R. A. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.3728-09.2009 · Cited by 358 · see citing works
Gong, B., Pan, Y., Vempati, P., Zhao, W., Knable, L., Ho, L., Wang, J., Sastre, M., Ono, K., Sauve, A. A., et al. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.12.005 · Cited by 345 · see citing works
Puzzo, D., Staniszewski, A., Deng, S., Privitera, L., Leznik, E., Liu, S., Zhang, H., Feng, Y., Palmeri, A., Landry, D. W., et al. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.0864-09.2009 · Cited by 333 · see citing works
Soluble Aβ Inhibits Specific Signal Transduction Cascades Common to the Insulin Receptor Pathway
Townsend, M., Mehta, T., & Selkoe, D. J. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m610390200 · Cited by 318 · see citing works
The role of CREB signaling in Alzheimer’s disease and other cognitive disorders
Saura, C. A., & Valero, J. (2011) · revneuro · doi:10.1515/rns.2011.018 · Cited by 312 · see citing works
Synaptic changes in Alzheimer’s disease and its models
Pozueta, J., Lefort, R., & Shelanski, M. L. (2012) · Neuroscience · doi:10.1016/j.neuroscience.2012.05.050 · Cited by 305 · see citing works
Arendash, G. W., Mori, T., Cao, C., Mamcarz, M., Runfeldt, M., Dickson, A., Rezai-Zadeh, K., Tan, J., Citron, B. A., Lin, X., et al. (2009) · Journal of Alzheimer s Disease · doi:10.3233/jad-2009-1087 · Cited by 308 · see citing works
Dysregulation of Histone Acetylation in the APP/PS1 Mouse Model of Alzheimer's Disease
Francis, Y. I., Fà, M., Ashraf, H., Zhang, H., Staniszewski, A., Latchman, D. S., & Arancio, O. (2009) · Journal of Alzheimer s Disease · doi:10.3233/jad-2009-1134 · Cited by 296 · see citing works
Selective phosphodiesterase inhibitors: a promising target for cognition enhancement
Reneerkens, O. A. H., Rutten, K., Steinbusch, H. W. M., Blokland, A., & Prickaerts, J. (2008) · Psychopharmacology · doi:10.1007/s00213-008-1273-x · Cited by 268 · see citing works
Phosphodiesterases as Therapeutic Targets for Alzheimer's Disease
García‐Osta, A., Cuadrado‐Tejedor, M., García, C., Oyarzábal, J., & Franco, R. (2012) · ACS Chemical Neuroscience · doi:10.1021/cn3000907 · Cited by 260 · see citing works
Lymphatic drainage system of the brain: A novel target for intervention of neurological diseases
Sun, B., Wang, L.-H., Yang, T., Sun, J., Mao, L., Yang, M., Yuan, H., Colvin, R. A., & Yang, X. (2017) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2017.08.007 · Cited by 255 · see citing works
Cho, S., Wood, A., & Bowlby, M. R. (2007) · Current Neuropharmacology · doi:10.2174/157015907780077105 · Cited by 242 · see citing works
Ricobaraza, A., Cuadrado‐Tejedor, M., Marco, S., Pérez‐Otaño, I., & García‐Osta, A. (2012) · Hippocampus · doi:10.1002/hipo.20883 · Cited by 239 · see citing works
Reversal of long-term dendritic spine alterations in Alzheimer disease models
Smith, D. L., Pozueta, J., Gong, B., Arancio, O., & Shelanski, M. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0908706106 · Cited by 229 · see citing works
Downregulation of CREB expression in Alzheimer's brain and in Aβ-treated rat hippocampal neurons
Pugazhenthi, S., Wang, M., Pham, S. T., Sze, C., & Eckman, C. B. (2011) · Molecular Neurodegeneration · doi:10.1186/1750-1326-6-60 · Cited by 240 · see citing works
Rodent models for Alzheimer’s disease drug discovery
Puzzo, D., Gulisano, W., Palmeri, A., & Arancio, O. (2015) · Expert Opinion on Drug Discovery · doi:10.1517/17460441.2015.1041913 · Cited by 222 · see citing works
Self-citationEnrichment improves cognition in AD mice by amyloid-related and unrelated mechanisms
Costa, D. A., Cracchiolo, J. R., Bachstetter, A. D., Hughes, T. F., Bales, K. R., Paul, S. M., Mervis, R. F., Arendash, G. W., & Potter, H. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2006.04.009 · Cited by 217 · see citing works
Exercise improves cognition and hippocampal plasticity in <i>APOE</i> ɛ4 mice
Nichol, K., Deeny, S. P., Seif, J., Camaclang, K., & Cotman, C. W. (2009) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2009.02.006 · Cited by 213 · see citing works
Behavioral assays with mouse models of Alzheimer's disease: Practical considerations and guidelines
Puzzo, D., Lee, L. S., Palmeri, A., Calabrese, G., & Arancio, O. (2014) · Biochemical Pharmacology · doi:10.1016/j.bcp.2014.01.011 · Cited by 214 · see citing works
Comery, T., Martone, R., Aschmies, S., Atchison, K., Diamantidis, G., Gong, X.-H., Zhou, H., Kreft, A., Pangalos, M., Sonnenberg-Reines, J., et al. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.2693-05.2005 · Cited by 204 · see citing works
Cuadrado‐Tejedor, M., Hervías, I., Ricobaraza, A., Puerta, E., Pérez-Roldán, J., García, C., Franco, R., Aguirre, N., & García‐Osta, A. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01517.x · Cited by 208 · see citing works
Trinchese, F., Fà, M., Liu, S., Zhang, H., Hidalgo, A., Schmidt, S. D., Yamaguchi, H., Yoshii, N., Mathews, P. M., Nixon, R. A., et al. (2008) · Journal of Clinical Investigation · doi:10.1172/jci34254 · Cited by 205 · see citing works
Brain-Targeted Proanthocyanidin Metabolites for Alzheimer's Disease Treatment
Wang, J., Ferruzzi, M. G., Ho, L., Blount, J. W., Janle, E. M., Gong, B., Pan, Y., Gowda, G. A. N., Raftery, D., Arrieta‐Cruz, I., et al. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.6437-11.2012 · Cited by 206 · see citing works
Ho, L., Ferruzzi, M. G., Janle, E. M., Wang, J., Gong, B., Chen, T., Lobo, J., Cooper, B. R., Wu, Q. L., Talcott, S. T., et al. (2012) · The FASEB Journal · doi:10.1096/fj.12-212118 · Cited by 204 · see citing works
Chapter 6 Regulation of hippocampus-dependent memory by cyclic AMP-dependent protein kinase
Abel, T., & Nguyen, P. V. (2008) · Progress in Brain Research · doi:10.1016/s0079-6123(07)00006-4 · Cited by 198 · see citing works
Neurotrophins, synaptic plasticity and dementia
Arancio, O., & Chao, M. V. (2007) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2007.03.013 · Cited by 193 · see citing works
Oligomeric amyloid-β peptide disrupts phosphatidylinositol-4,5-bisphosphate metabolism
Berman, D. E., Dall'Armi, C., Voronov, S. V., McIntire, L. B. J., Zhang, H., Moore, A. Z., Staniszewski, A., Arancio, O., Kim, T.-W., & Di Paolo, G. (2008) · Nature Neuroscience · doi:10.1038/nn.2100 · Cited by 199 · see citing works
The novel selective PDE9 inhibitor BAY 73-6691 improves learning and memory in rodents
van der Staay, F. J., Rutten, K., Bärfacker, L., DeVry, J., Erb, C., Heckroth, H., Karthaus, D., Tersteegen, A., van Kampen, M., Blokland, A., et al. (2008) · Neuropharmacology · doi:10.1016/j.neuropharm.2008.07.005 · Cited by 180 · see citing works
Li, S., Jin, M., Zhang, D., Yang, T., Koeglsperger, T., Fu, H., & Selkoe, D. J. (2013) · Neuron · doi:10.1016/j.neuron.2012.12.040 · Cited by 177 · see citing works
Valor, L. M., Viosca, J., López‐Atalaya, J. P., & Barco, Á. (2013) · Current Pharmaceutical Design · doi:10.2174/13816128113199990382 · Cited by 168 · see citing works
The expanding role of BDNF: a therapeutic target for Alzheimer's disease?
Fumagalli, F., Racagni, G., & Riva, M. A. (2005) · The Pharmacogenomics Journal · doi:10.1038/sj.tpj.6500337 · Cited by 173 · see citing works
Prickaerts, J., Heckman, P. R. A., & Blokland, A. (2017) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2017.1364360 · Cited by 172 · see citing works
Gong, B., Radulovic, M., Figueiredo‐Pereira, M. E., & Cardozo, C. P. (2016) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2016.00004 · Cited by 167 · see citing works
Li, Q., Zhao, H., Zhang, Z. F., Liu, Z. G., Pei, X., Wang, J. B., & Li, Y. (2009) · Neuroscience · doi:10.1016/j.neuroscience.2009.07.014 · Cited by 165 · see citing works
Yang, J., Wang, Z., Cai, H.-Y., Li, Y., Hu, M.-M., Wu, M., & Qi, J. (2018) · Neuroscience Bulletin · doi:10.1007/s12264-018-0268-9 · Cited by 161 · see citing works
Multi-faced neuroprotective effects of Ginsenoside Rg1 in an Alzheimer mouse model
Fang, F., Chen, X., Huang, T., Lue, L., Luddy, J. S., & Yan, S. S. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2011.10.004 · Cited by 160 · see citing works
Voronov, S. V., Frere, S. G., Giovedi, S., Pollina, E. A., Borel, C., Zhang, H., Schmidt, C., Akeson, E. C., Wenk, M. R., Cimasoni, L., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0803756105 · Cited by 174 · see citing works
Marcade, M., Bourdin, J., Loiseau, N., Peillon, H., Rayer, A., Drouin, D., Schweighoffer, F., & Désiré, L. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05396.x · Cited by 155 · see citing works
Ledeboer, A., Hutchinson, M. R., Watkins, L. R., & Johnson, K. W. (2007) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.16.7.935 · Cited by 153 · see citing works
Zhang, J., Guo, J., Zhao, X., Chen, Z., Wang, G., Liu, A., Wang, Q., Zhou, W., Xu, Y., & Wang, C. (2013) · Behavioural Brain Research · doi:10.1016/j.bbr.2013.05.017 · Cited by 152 · see citing works
Kelly, M. P. (2017) · Cellular Signalling · doi:10.1016/j.cellsig.2017.11.004 · Cited by 147 · see citing works
Wang, C., Yang, X., Zhuo, Y., Zhou, H., Lin, H.-B., Cheng, Y., Xu, J., & Zhang, H. (2011) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145711000836 · Cited by 150 · see citing works
PDE4 as a target for cognition enhancement
Richter, W., Menniti, F. S., Zhang, H., & Conti, M. (2013) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2013.818656 · Cited by 148 · see citing works
Genetic reduction of Nrf2 exacerbates cognitive deficits in a mouse model of Alzheimer’s disease
Branca, C., Ferreira, E., Nguyen, T.-V., Doyle, K., Caccamo, A., & Oddo, S. (2017) · Human Molecular Genetics · doi:10.1093/hmg/ddx361 · Cited by 139 · see citing works
Synaptic Therapy in Alzheimer's Disease: A CREB-centric Approach
Teich, A. F., Nicholls, R. E., Puzzo, D., Fiorito, J., Purgatorio, R., Fà, M., & Arancio, O. (2015) · Neurotherapeutics · doi:10.1007/s13311-014-0327-5 · Cited by 147 · see citing works
Modulation of the cAMP signaling pathway after traumatic brain injury
Atkins, C. M., Oliva, A. A., Alonso, O. F., Pearse, D. D., Bramlett, H. M., & Dietrich, W. D. (2007) · Experimental Neurology · doi:10.1016/j.expneurol.2007.08.011 · Cited by 140 · see citing works
GEBR-7b, a novel PDE4D selective inhibitor that improves memory in rodents at non-emetic doses
Bruno, O., Fedele, E., Prickaerts, J., Parker, L. A., Canepa, E., Brullo, C., Cavallero, A., Gardella, E., Balbi, A., Domenicotti, C., et al. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01524.x · Cited by 138 · see citing works
Marchetti, C., & Marie, H. (2011) · Reviews in the Neurosciences · doi:10.1515/rns.2011.035 · Cited by 133 · see citing works
Matsuzaki, K., Yamakuni, T., Hashimoto, M., Haque, A. M., Shido, O., Mimaki, Y., Sashida, Y., & Ohizumi, Y. (2006) · Neuroscience Letters · doi:10.1016/j.neulet.2006.02.077 · Cited by 135 · see citing works
Liang, Z., Liu, F., Grundke, I., Iqbal, K., & Gong, C. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.04942.x · Cited by 134 · see citing works
Spines, plasticity, and cognition in Alzheimer's model mice
Spires-Jones, T., & Knafo, S. (2012) · Neural Plasticity · doi:10.1155/2012/319836 · Cited by 133 · see citing works
Guo, H., Cheng, Y., Wang, C., Wu, J., Zou, Z., Niu, B., Yu, H. M., Wang, H., & Xu, J. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.01.004 · Cited by 133 · see citing works
Rutten, K., Prickaerts, J., & Blokland, A. (2005) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2005.09.002 · Cited by 132 · see citing works
Alzheimer's β-Secretase (BACE1) Regulates the cAMP/PKA/CREB Pathway Independently of β-Amyloid
Chen, Y., Huang, X., Zhang, Y., Rockenstein, E. M., Bu, G., Golde, T. E., Masliah, E., & Xu, H. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.0757-12.2012 · Cited by 131 · see citing works
Novel Phosphodiesterase Inhibitors for Cognitive Improvement in Alzheimer’s Disease
Wu, Y., Li, Z., Huang, Y., Wu, D., & Luo, H. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.7b01370 · Cited by 129 · see citing works
España, J., Valero, J., Miñano-Molina, A. J., Masgrau, R., Martín, E., Guardia‐Laguarta, C., Lleó, A., Giménez‐Llort, L., Rodrı́guez-Álvarez, J., & Saura, C. A. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.2154-10.2010 · Cited by 127 · see citing works
Wang, J., Bi, W., Cheng, A., Freire, D., Vempati, P., Zhao, W., Gong, B., Janle, E. M., Chen, T., Ferruzzi, M. G., et al. (2014) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2014.00042 · Cited by 126 · see citing works
Sierksma, A. S. R., van den Hove, D., Pfau, F., Philippens, M., Bruno, O., Fedele, E., Ricciarelli, R., Steinbusch, H. W. M., Vanmierlo, T., & Prickaerts, J. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.09.015 · Cited by 125 · see citing works
The glial modulatory drug AV411 attenuates mechanical allodynia in rat models of neuropathic pain
Ledeboer, A., Liu, T., Shumilla, J. A., Mahoney, J. H., Vijay, S., Gross, M. I., Vargas, J. A., Sultzbaugh, L., Claypool, M. D., Sanftner, L. M., et al. (2006) · Neuron Glia Biology · doi:10.1017/s1740925x0700035x · Cited by 122 · see citing works
Multitarget Therapeutic Strategies for Alzheimer’s Disease: Review on Emerging Target Combinations
Maramai, S., Benchekroun, M., Gabr, M. T., & Yahiaoui, S. (2020) · BioMed Research International · doi:10.1155/2020/5120230 · Cited by 121 · see citing works
Phosphodiesterase-4 (PDE4) Molecular Pharmacology and Alzheimer's Disease
Gurney, M. E., D'Amato, E. C., & Burgin, A. B. (2015) · Neurotherapeutics · doi:10.1007/s13311-014-0309-7 · Cited by 121 · see citing works
Current therapeutic targets for the treatment of Alzheimer’s disease
Grill, J. D., & Cummings, J. L. (2010) · Expert Review of Neurotherapeutics · doi:10.1586/ern.10.29 · Cited by 121 · see citing works
Rutten, K., Misner, D., Works, M. G., Blokland, A., Novak, T. J., Santarelli, L., & Wallace, T. L. (2008) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2008.06349.x · Cited by 119 · see citing works
Advances in the Development of Phosphodiesterase-4 Inhibitors
Peng, T., Qi, B., He, J., Ke, H., & Shi, J. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b02170 · Cited by 119 · see citing works
Echeverrı́a, V., Clerman, A., & Doré, S. (2005) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2005.04427.x · Cited by 119 · see citing works
Iijima‐Ando, K., Hearn, S., Shenton, C., Gatt, A., Zhao, L., & Iijima, K. (2009) · PLoS ONE · doi:10.1371/journal.pone.0008310 · Cited by 119 · see citing works
Beneficial effects of rolipram in the R6/2 mouse model of Huntington's disease
DeMarch, Z., Giampà, C., Patassini, S., Bernardi, G., & Fusco, F. R. (2008) · Neurobiology of Disease · doi:10.1016/j.nbd.2008.02.010 · Cited by 117 · see citing works
Liu, M., Chen, F., Sha, L., Wang, S., Lin, T., Yao, L., He, M., Yao, Z., Liu, H., Zhu, Z., et al. (2013) · Molecular Neurobiology · doi:10.1007/s12035-013-8608-2 · Cited by 117 · see citing works
Rutten, K., van Donkelaar, E. L., Ferrington, L., Blokland, A., Bollen, E., Steinbusch, H. W. M., Kelly, P. A., & Prickaerts, J. (2009) · Neuropsychopharmacology · doi:10.1038/npp.2009.24 · Cited by 114 · see citing works
Increased PKA signaling disrupts recognition memory and spatial memory: role in Huntington's disease
Giralt, A., Saavedra, A., Carretón, O., Xifró, X., Alberch, J., & Pérez‐Navarro, E. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr351 · Cited by 113 · see citing works
Optogenetic stimulation of dentate gyrus engrams restores memory in Alzheimer's disease mice
Perusini, J. N., Cajigas, S. A., Cohensedgh, O., Lim, S. C., Pavlova, I. P., Donaldson, Z. R., & Denny, C. A. (2017) · Hippocampus · doi:10.1002/hipo.22756 · Cited by 115 · see citing works
Sanders, O. D., & Rajagopal, L. (2020) · Journal of Alzheimer s Disease Reports · doi:10.3233/adr-200191 · Cited by 115 · see citing works
Fiorito, J., Saeed, F., Zhang, H., Staniszewski, A., Feng, Y., Francis, Y. I., Rao, S. R., Thakkar, D. M., Deng, S., Landry, D. W., et al. (2012) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2012.12.009 · Cited by 113 · see citing works
Peixoto, C. A., Nunes, A. K. S., & García‐Osta, A. (2015) · Mediators of Inflammation · doi:10.1155/2015/940207 · Cited by 112 · see citing works
The PDE4 inhibitor roflumilast improves memory in rodents at non-emetic doses
Vanmierlo, T., Creemers, P., Akkerman, S., van Duinen, M. A., Sambeth, A., Vry, J. D., Uz, T., Blokland, A., & Prickaerts, J. (2016) · Behavioural Brain Research · doi:10.1016/j.bbr.2016.01.031 · Cited by 112 · see citing works
ADDLs and the signaling web that leads to Alzheimer’s disease
Krafft, G. A., & Klein, W. L. (2010) · Neuropharmacology · doi:10.1016/j.neuropharm.2010.07.012 · Cited by 111 · see citing works
Targeting Synaptic Plasticity in Experimental Models of Alzheimer’s Disease
Mango, D., Saidi, A., Cisale, G. Y., Feligioni, M., Corbo, M., & Nisticò, R. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00778 · Cited by 109 · see citing works
Monti, B., Berteotti, C., & Contestabile, A. (2006) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300813 · Cited by 109 · see citing works
Phosphodiesterase-4 enzyme as a therapeutic target in neurological disorders
Bhat, A., Ray, B., Mahalakshmi, A. M., Tuladhar, S., Nandakumar, D., Srinivasan, M., Essa, M. M., Chidambaram, S. B., Guillemin, G. J., & Sakharkar, M. K. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.105078 · Cited by 107 · see citing works
Evidence of Aβ‐ and transgene‐dependent defects in ERK‐CREB signaling in Alzheimer’s models
Ma, Q., Harris‐White, M. E., Ubeda, O. J., Simmons, M., Beech, W. K., Lim, G. P., Teter, B., Frautschy, S. A., & Cole, G. M. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.04869.x · Cited by 110 · see citing works
Phosphodiesterases in the Central Nervous System: Implications in Mood and Cognitive Disorders
Xu, Y., Zhang, H., & O’Donnell, J. M. (2011) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-17969-3_19 · Cited by 104 · see citing works
Choi, C. H., Schoenfeld, B. P., Bell, A. J., Hinchey, P., Kollaros, M., Gertner, M. J., Woo, N. H., Tranfaglia, M. R., Bear, M. F., Zukin, R. S., et al. (2010) · Brain Research · doi:10.1016/j.brainres.2010.11.032 · Cited by 104 · see citing works
Crtc1 Activates a Transcriptional Program Deregulated at Early Alzheimer's Disease-Related Stages
Parra‐Damas, A., Valero, J., Chen, M., España, J., Martín, E., Ferrer, I., Rodrı́guez-Álvarez, J., & Saura, C. A. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.5288-13.2014 · Cited by 104 · see citing works
Amyloid β peptide adversely affects spine number and motility in hippocampal neurons
Shrestha, B. R., Vitolo, O. V., Joshi, P., Lordkipanidze, T. G., Shelanski, M. L., & Dunaevsky, A. (2006) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2006.07.011 · Cited by 103 · see citing works
Cheng, Y., Wang, C., Lin, H.-B., Li, Y., Huang, Y., Xu, J., & Zhang, H. (2010) · Psychopharmacology · doi:10.1007/s00213-010-1943-3 · Cited by 99 · see citing works
The Role of Phosphodiesterases in Schizophrenia
Siuciak, J. A. (2008) · CNS Drugs · doi:10.2165/0023210-200822120-00002 · Cited by 98 · see citing works
Synaptic plasticity in Alzheimer’s disease and healthy aging
Torres, D. M. C., & Cárdenas, F. P. (2020) · Reviews in the Neurosciences · doi:10.1515/revneuro-2019-0058 · Cited by 98 · see citing works
Targeting Synaptic Dysfunction in Alzheimer’s Disease Therapy
Nisticò, R., Pignatelli, M., Piccinin, S., Mercuri, N. B., & Collingridge, G. L. (2012) · Molecular Neurobiology · doi:10.1007/s12035-012-8324-3 · Cited by 97 · see citing works
Bitner, R. S., Bunnelle, W. H., Decker, M. W., Drescher, K. U., Kohlhaas, K. L., Markosyan, S., Marsh, K. C., Nikkel, A. L., Browman, K., Radek, R., et al. (2010) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.110.167213 · Cited by 97 · see citing works
PDE4B as a microglia target to reduce neuroinflammation
Pearse, D. D., & Hughes, Z. A. (2016) · Glia · doi:10.1002/glia.22986 · Cited by 97 · see citing works
Failures to reconsolidate memory in a mouse model of Alzheimer’s disease
Ohno, M. (2009) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2009.05.001 · Cited by 95 · see citing works
- Authors
- Gong, B., Vitolo, O. V., Trinchese, F., Liu, S., Shelanski, M., & Arancio, O.
- Affiliations
- Nathan Kline Institute for Psychiatric Research (US)
- Columbia University (US)
- Venue
- Journal of Clinical Investigation
- Published
- 2004-12-01
- Volume
- 114
- Issue
- 11
- Pages
- 1624-1634
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC529285
- OpenAlex
- W2034986487
- Cited by
- 442
- References
- 60
- Citations by year
- 2026: 12 · 2025: 14 · 2024: 16 · 2023: 15 · 2022: 11 · 2021: 13 · 2020: 21 · 2019: 20 · 2018: 17 · 2017: 33 · 2016: 17 · 2015: 20 · 2014: 28 · 2013: 23 · 2012: 23
- FWCI
- 12.13
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Alzheimer's Association
- University of Minnesota
- York University
- National Institutes of Health
- School of Medicine, New York University
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, rolipram, amyloid-beta 42, synaptic plasticity, long-term potentiation, contextual learning, memory impairment, phosphodiesterase-4 inhibitors, cAMP/PKA/CREB signaling, synaptic transmission, APP/PS1 double transgenic mice
- MeSH terms
- Alzheimer Disease, Animals, Cognition, Disease Models, Animal, Hippocampus, Humans, Learning, Male, Membrane Proteins, Mice, Transgenic, Synaptic Transmission, Phosphodiesterase Inhibitors, Amyloid beta-Protein Precursor, Cyclic AMP Response Element-Binding Protein, Long-Term Potentiation, Rolipram, Mice, Presenilin-1, In Vitro Techniques
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