Chronic phosphodiesterase type 2 inhibition improves memory in the APPswe/PS1dE9 mouse model of Alzheimer's disease

Sierksma, Annerieke; Rutten, Kris; Sydlik, Sebastian; Rostamian, Somayeh; Steinbusch, Harry W.M.; Hove, Daniël L.A. van den; Prickaerts, Jos

doi:10.1016/j.neuropharm.2012.06.048

Cited by 72 publications

(47 citation statements)

References 90 publications

(85 reference statements)

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“…Caffeine intake has been associated with a lower incidence of AD in humans, and it has been revealed that caffeine shifts the balance between neurodegeneration and neuronal survival towards the stimulation of pro-survival cascades and the inhibition of pro-apoptotic pathways in the striatum by increasing PKA and pCREB (25). In addition, several lines of evidence indicate that PKA/CREB are involved in Aβ-trigged disruption of synaptic plasticity in AD (26), and the overexpression of BACE1 reduces the activity of PKA and pCREB, contributing to the memory and cognitive deficits typical of AD (27). Therefore, activation of the PKA/CREB pathway is beneficial against AD.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-29c targets β-site amyloid precursor protein-cleaving enzyme 1 and has a neuroprotective role in vitro and in vivo

Yang

Song

Zhou

et al. 2015

Molecular Medicine Reports

102

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Abstract. Alzheimer's disease (AD), characterized by β-amyloid deposition and neurodegeneration, is the most common cause of dementia worldwide. Emerging evidence suggests that ectopic expression of micro (mi)RNAs is involved in the pathogenesis of AD. There is increasing evidence that miRNAs expressed in the brain are involved in neuronal development, survival and apoptosis. The expression of β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) is regulated by dysregulated miRNAs in the brain. The present study determined the expression levels of the miRNA-29 (miR-29) family in peripheral blood samples of patients with AD and demonstrated a marked decrease in the expression of miR-29c compared with age-matched controls. In addition, a significant increase in the exprssion of BACE1 was observed in the peripheral blood of patients with AD. Correlation analysis revealed that the expression of miR-29c was negatively correlated with the protein expression of BACE1 in the peripheral blood samples from patients with AD. The present study also investigated the role of miR-29 on hippocampal neurons in vitro and in vivo. The results demonstrated that the upregulation of miR-29c promoted learning and memory behaviors in SAMP8 mice, at least partially, by increasing the activity of protein kinase A/cAMP response element-binding protein, involved in neuroprotection. This evidence suggested that miR-29c may be a promising potential therapeutic target against AD.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-29c targets β-site amyloid precursor protein-cleaving enzyme 1 and has a neuroprotective role in vitro and in vivo

Yang

Song

Zhou

et al. 2015

Molecular Medicine Reports

102

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“…Much of the early preclinical work on PDE2 and cognition in aged rodents and mouse models of AD was done using the promising BAY 60-7550 compound (e.g. [56][57][58]), which however never made it to the clinic. Another early compound was ND-7001 (developed by Université de Strasbourg/Neuro3d), which only made it up to Phase I clinical trials to investigate safety, tolerability and pharmacokinetics (for the indication anxiety and depression).…”

Section: Phosphodiesterasementioning

confidence: 99%

Investigational phosphodiesterase inhibitors in phase I and phase II clinical trials for Alzheimer’s disease

Prickaerts

Heckman

Blokland

2017

Expert Opinion on Investigational Drugs

Self Cite

146

168

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Introduction: Phosphodiesterase (PDE) inhibitors improve signaling pathways in brain circuits by increasing intracellular cyclic adenosine monophosphate (cAMP) and/or cyclic guanosine monophosphate (cGMP). In the last decade, the first clinical studies investigating selective PDE inhibitors in Alzheimer's disease (AD) have been initiated, based on their positive effects on cognitive processes and neuroprotection in numerous animal studies. Areas covered: This article reviews the clinical studies investigating the pro-cognitive/neuroprotective effects of PDE inhibitors in patients with AD, as well as in age-associated memory impaired elderly and patients with mild cognitive impairment (MCI), the prodromal stage of AD. PDE inhibitors will also be discussed with respect to adverse effects including safety and tolerability. Expert opinion: The limited available data of clinical studies with PDE inhibitors tested in different populations of AD patients do not allow the drawing of any concrete conclusion yet. Currently, studies with a PDE3 (cilostazol) or PDE9 inhibitor (BI 409,306) are still ongoing in patients with MCI or AD, respectively. Studies with PDE4 inhibitors (HT-0712, roflumilast and BPN14770) in healthy elderly and elderly with age-associated memory impairments indicate that the optimum dose and/or inhibiting the most relevant PDE isoform hold great promise when tested in the appropriate population of patients with MCI or AD eventually. ARTICLE HISTORY

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“…Indeed, some experimental studies have demonstrated a negative impact of chronic stress during various stages of life (including prenatal phase) on some aspects of AD pathology (Postnatal phase [15,16]; prenatal phase [17][18][19]). However, presently, few studies have been involved in the learning and memory impairments, and neuropathology elicited by the CPS and the chronic offspring stress (COS) exposures simultaneously, particularly in adult male APPswe/PS1dE9 offspring.…”

Section: Introductionmentioning

confidence: 99%

The Synergistic Roles of the Chronic Prenatal and Offspring Stress Exposures in Impairing Offspring Learning and Memory

Tang

Cheng

Wang

et al. 2016

JAD

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Abstract. In Alzheimer's disease (AD), extensive experimental studies have demonstrated a negative impact of chronic stress during various stages of life (including prenatal phase) on some aspects of AD pathology. Nevertheless, presently, few studies have been involved in the learning and memory impairments, as well as neuropathology elicited by the chronic prenatal stress (CPS) and the chronic offspring stress (COS) exposures simultaneously, particularly for the adult male APPswe/PS1dE9 murine offspring. Therefore, the aim of the present study was to investigate the influence of CPS on learning and memory impairments induced by COS in 6-month-old male APPswe/PS1dE9 offspring mice and the related mechanism. Our study firstly demonstrates that 14-day exposure to CPS could exacerbate the learning and memory impairments, as well as neuropathological damages in the CA3 regions of the hippocampus and cortex neurons, which is induced by the 28-day exposure to COS in 6-month-old male APPswe/PS1dE9 offspring mice. In addition, CPS could potentiate the production of A␤PP, A␤ 42, and corticosterone in 6-month-old male APPswe/PS1dE9 offspring that also suffer COS. In conclusion, our novel findings strongly implicate the synergistic roles of the CPS and COS exposures in impairing offspring learning and memory. Moreover, CPS potentiating the production of A␤ 42 might be mediated by glucocorticoids through increasing the expression of APP and BACE1 gene.

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Chronic phosphodiesterase type 2 inhibition improves memory in the APPswe/PS1dE9 mouse model of Alzheimer's disease

Cited by 72 publications

References 90 publications

MicroRNA-29c targets β-site amyloid precursor protein-cleaving enzyme 1 and has a neuroprotective role in vitro and in vivo

MicroRNA-29c targets β-site amyloid precursor protein-cleaving enzyme 1 and has a neuroprotective role in vitro and in vivo

Investigational phosphodiesterase inhibitors in phase I and phase II clinical trials for Alzheimer’s disease

The Synergistic Roles of the Chronic Prenatal and Offspring Stress Exposures in Impairing Offspring Learning and Memory

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