Inhibition of phosphodiesterase-5 rescues age-related impairment of synaptic plasticity and memory

Palmeri, Agostino; Privitera, Lucia; Giunta, Salvatore; Loreto, Carla; Puzzo, Daniela

doi:10.1016/j.bbr.2012.10.060

Cited by 69 publications

(50 citation statements)

References 62 publications

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“…Furthermore, in the formation of several types of long-term memory, among which object recognition, the necessity of CRE gene-driven protein synthesis paradigms has been extensively reported. Previous studies demonstrated increased hippocampal levels of phosphorylated CREB after in vivo subchronic rolipram treatment (Monti et al, 2006), as well as after in vitro bath application of sildenafil on tetanized hippocampal slices in APP/PS1 mice (Puzzo et al, 2009) and aged mice (Palmeri et al, 2013). Although the transcriptional program of CREB phosphorylation is still largely unclear, it is known that the target genes of CREB are functionally heterogeneous, including channel subunits, other transcription factors, and growth factors (Sakamoto et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Improved Long-Term Memory via Enhancing cGMP-PKG Signaling Requires cAMP-PKA Signaling

Bollen

Puzzo

Rutten

et al. 2014

Neuropsychopharmacol

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103

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Memory consolidation is defined by the stabilization of a memory trace after acquisition, and consists of numerous molecular cascades that mediate synaptic plasticity. Commonly, a distinction is made between an early and a late consolidation phase, in which early refers to the first hours in which labile synaptic changes occur, whereas late consolidation relates to stable and long-lasting synaptic changes induced by de novo protein synthesis. How these phases are linked at a molecular level is not yet clear. Here we studied the interaction of the cyclic nucleotide-mediated pathways during the different phases of memory consolidation in rodents. In addition, the same pathways were studied in a model of neuronal plasticity, long-term potentiation (LTP). We demonstrated that cGMP/protein kinase G (PKG) signaling mediates early memory consolidation as well as early-phase LTP, whereas cAMP/protein kinase A (PKA) signaling mediates late consolidation and late-phase-like LTP. In addition, we show for the first time that early-phase cGMP/PKG signaling requires late-phase cAMP/PKA-signaling in both LTP and long-term memory formation.

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Section: Discussionmentioning

confidence: 99%

Improved Long-Term Memory via Enhancing cGMP-PKG Signaling Requires cAMP-PKA Signaling

Bollen

Puzzo

Rutten

et al. 2014

Neuropsychopharmacol

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103

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“…Elderly mice are less capable to counteract oxidative stress in comparison to the young mice (Villeda et al, 2014). The pharmacological agents such as tadalafil could bring different results in these age groups since other PDE-5 inhibitor (sildenafil) showed vital role in age-related cognitive dysfunction in mouse model of aging (Palmeri et al, 2013).…”

Section: Aim Of the Studymentioning

confidence: 99%

Tadalafil enhances working memory, and reduces hippocampal oxidative stress in both young and aged mice

Al-Amin

Hasan

Alam

et al. 2014

European Journal of Pharmacology

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“…Several lines of evidence are consistent with this hypothesis: 1) the inhibition of 1 of the components of the NO/cGMP/PKG pathway suppresses CREB phosphorylation [94,116,117]; 2) the increase of phospho-CREB during synaptic plasticity is blocked by Aβ in cultured cortical neurons [118], in cultured hippocampal neurons [3], and in hippocampal tetanized slices treated with Aβ [110]; and 3) stimulation of the NO/sGC/ cGMP pathway restores levels of phospho-CREB [112,113]. Because of these findings, and considering that the NO cascade is downregulated during aging and in neurodegenerative disorders [112,113,[119][120][121][122], an increasing number of studies have focused on therapeutic strategies aimed to regulate this signaling pathway.…”

Section: The Erk1/2 Mitogen-activated Protein Kinase Pathwaymentioning

confidence: 75%

“…Over the past few years, our group and others have demonstrated that treatment with PDE5-Is rescues synaptic and memory deficits in the APP/ PS1 mouse model of AD, restoring phospho-CREB levels and decreasing Aβ load [112,128]. The PDE5-I sildenafil also exerts the same beneficial effect in a physiological mouse model of aging [113], where it also inhibits apoptosis and increases antiapoptotic molecules Bcl2 and BDNF [129].…”

Section: The Erk1/2 Mitogen-activated Protein Kinase Pathwaymentioning

confidence: 94%

“…This occurs through Aβ-mediated inhibition of NO-induced CREB phosphorylation [105][106][107][108][109][110][111], and toxicity may be exacerbated because the NO/cGMP signaling pathway exerts a protective role against Aβ-mediated neurotoxicity [112][113][114]. We have previously demonstrated that the use of NO donors or cGMP agonists was able to rescue the Aβ-induced impairment of LTP and CREB phosphorylation, whereas sGC or PKG inhibition suppresses this neuroprotective effect [110].…”

Section: The Erk1/2 Mitogen-activated Protein Kinase Pathwaymentioning

confidence: 99%

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Synaptic Therapy in Alzheimer's Disease: A CREB-centric Approach

et al. 2015

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Therapeutic attempts to cure Alzheimer's disease (AD) have failed, and new strategies are desperately needed. Motivated by this reality, many laboratories (including our own) have focused on synaptic dysfunction in AD because synaptic changes are highly correlated with the severity of clinical dementia. In particular, memory formation is accompanied by altered synaptic strength, and this phenomenon (and its dysfunction in AD) has been a recent focus for many laboratories. The molecule cyclic adenosine monophosphate response element-binding protein (CREB) is at a central converging point of pathways and mechanisms activated during the processes of synaptic strengthening and memory formation, as CREB phosphorylation leads to transcription of memory-associated genes. Disruption of these mechanisms in AD results in a reduction of CREB activation with accompanying memory impairment. Thus, it is likely that strategies aimed at these mechanisms will lead to future therapies for AD. In this review, we will summarize literature that investigates 5 possible therapeutic pathways for rescuing synaptic dysfunction in AD: 4 enzymatic pathways that lead to CREB phosphorylation (the cyclic adenosine monophosphate cascade, the serine/threonine kinases extracellular regulated kinases 1 and 2, the nitric oxide cascade, and the calpains), as well as histone acetyltransferases and histone deacetylases (2 enzymes that regulate the histone acetylation necessary for gene transcription).

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Inhibition of phosphodiesterase-5 rescues age-related impairment of synaptic plasticity and memory

Cited by 69 publications

References 62 publications

Improved Long-Term Memory via Enhancing cGMP-PKG Signaling Requires cAMP-PKA Signaling

Improved Long-Term Memory via Enhancing cGMP-PKG Signaling Requires cAMP-PKA Signaling

Tadalafil enhances working memory, and reduces hippocampal oxidative stress in both young and aged mice

Synaptic Therapy in Alzheimer's Disease: A CREB-centric Approach

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