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Amyloid β-induced impairments on mitochondrial dynamics, hippocampal neurogenesis, and memory are restored by phosphodiesterase 7 inhibition

Overview of attention for article published in Alzheimer's Research & Therapy, February 2018
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Title
Amyloid β-induced impairments on mitochondrial dynamics, hippocampal neurogenesis, and memory are restored by phosphodiesterase 7 inhibition
Published in
Alzheimer's Research & Therapy, February 2018
DOI 10.1186/s13195-018-0352-4
Pubmed ID
Authors

Fernando Bartolome, Macarena de la Cueva, Consuelo Pascual, Desiree Antequera, Tamara Fernandez, Carmen Gil, Ana Martinez, Eva Carro

Abstract

The phosphodiesterase (PDE) 7 inhibitor S14 is a cell-permeable small heterocyclic molecule that is able to cross the blood-brain barrier. We previously found that intraperitoneal treatment with S14 exerted neuroprotection in an Alzheimer's disease (AD) model (in APP/PS1 mice). The objective of this study was to investigate the neurogenic and cellular effects of oral administration of S14 on amyloid β (Aβ) overload. We orally administered the PDE7 inhibitor S14 (15 mg/kg/day) or vehicle in 6-month-old APP/PS1 mice. After 5 weeks of S14 treatment, we evaluated cognitive functions and brain tissues. We also assessed the effects of S14 on the Aβ-treated human neuroblastome SH-SY5Y cell line. Targeting the cyclic adenosine monophosphate (cAMP)/cAMP-response element binding protein (CREB) pathway, S14 rescued cognitive decline by improving hippocampal neurogenesis in APP/PS1 transgenic mice. Additionally, S14 treatment reverted the Aβ-induced reduction in mitochondrial mass in APP/PS1 mice and in the human neuroblastoma SH-SY5Y cells co-exposed to Aβ. The restoration of the mitochondrial mass was found to be a dual effect of S14: a rescue of the mitochondrial biogenesis formerly slowed down by Aβ overload, and a reduction in the Aβ-increased mitochondrial clearance mechanism of mitophagy. Here, we show new therapeutic effects of the PDE7 inhibitor, confirming S14 as a potential therapeutic drug for AD.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 63 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 63 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 10 16%
Student > Ph. D. Student 9 14%
Student > Bachelor 6 10%
Student > Doctoral Student 4 6%
Student > Master 4 6%
Other 6 10%
Unknown 24 38%
Readers by discipline Count As %
Neuroscience 12 19%
Biochemistry, Genetics and Molecular Biology 11 17%
Pharmacology, Toxicology and Pharmaceutical Science 5 8%
Medicine and Dentistry 2 3%
Unspecified 1 2%
Other 5 8%
Unknown 27 43%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 03 March 2018.
All research outputs
#20,466,701
of 23,025,074 outputs
Outputs from Alzheimer's Research & Therapy
#1,213
of 1,244 outputs
Outputs of similar age
#292,574
of 331,055 outputs
Outputs of similar age from Alzheimer's Research & Therapy
#33
of 35 outputs
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So far Altmetric has tracked 1,244 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 25.9. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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We're also able to compare this research output to 35 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.