Cited by 452Alzheimer's disease research and treatmentsNeuroscience and Neuropharmacology ResearchDementia and Cognitive Impairment Research

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Persistent improvement in synaptic and cognitive functions in an Alzheimer mouse model after rolipram treatment

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Gong, Bing, Vitolo, Ottavio V., Trinchese, Fabrizio, Liu, Shumin, Shelanski, Michael, Arancio, Ottavio·2004·Journal of Clinical Investigation

DOI 10.1172/jci22831PMC PMC529285

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Abstract

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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BackgroundInfluential
Phosphodiesterase Type 4 Inhibition Does Not Restore Ocular Dominance Plasticity in a Ferret Model of Fetal Alcohol Spectrum Disorders
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Transcriptome-wide association study of Alzheimer disease reveals many differentially expressed genes and multiple biological pathways in brain tissue from African American donorsPreprint
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Rolipram and pentoxifylline combination ameliorates the morphological abnormalities of dorsal root ganglion neurons in experimental diabetic neuropathy by reducing mitochondrial dysfunction and apoptosis
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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)
ORCID: Gong, Bing
Vitolo, Ottavio V.
Trinchese, Fabrizio
Liu, Shumin
Shelanski, Michael
Arancio, Ottavio
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2004-12-01
Volume: 114
Issue: 11
Pages: 1624-1634
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci22831
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: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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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Persistent improvement in synaptic and cognitive functions in an Alzheimer mouse model after rolipram treatment

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