Evidence map›Paper›PMID 37208298›Full record

ArticleThe international journal of neuropsychopharmacology2023

Characterization of 2 Novel Phosphodiesterase 2 Inhibitors Hcyb1 and PF-05180999 on Depression- and Anxiety-Like Behavior.

Yuqing Yan, Yuhan Zhao, Yue Lu, Abhinav P Acharya, Wei Wang, Chang-Guo Zhan, Jianghong Ye, Fu Du, Xiongwei Zhu, Ying Xu

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in The international journal of neuropsychopharmacology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 2 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed, 1 pooled it
0.6field-weighted citation impact, top 30% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 1 synthesis or guideline pooled it, 4 citations in OpenAlex.

  1. Pooled it
  2. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 5 institutions in 1 country.

Yuqing YanDepartment of Anesthesiology, Rutgers, the State University of New Jersey, Newark, New Jersey, USA.
Yuhan ZhaoDepartment of Anesthesiology, Rutgers, the State University of New Jersey, Newark, New Jersey, USA.
Yue LuDepartment of Anesthesiology, Rutgers, the State University of New Jersey, Newark, New Jersey, USA.
Abhinav P AcharyaChemical Engineering School for the Engineering of Matter, Transport, and Energy, Arizona State University, Tempe, Arizona, USA.
Wei WangDepartment of Pharmacology and Toxicology, Arizona Center for Drug Discovery, College of Pharmacy, University of Arizona, Tucson, Arizona, USA.
Chang-Guo ZhanDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky, USA.ORCID 0000-0002-4128-7269
Jianghong YeDepartment of Anesthesiology, Rutgers, the State University of New Jersey, Newark, New Jersey, USA.
Fu DuFD NeuroTechnologies Consulting and Services, Inc., Columbia, Maryland, USA.
Xiongwei ZhuDepartment of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
Ying XuDepartment of Anesthesiology, Rutgers, the State University of New Jersey, Newark, New Jersey, USA.
Rutgers, The State University of New Jersey · USArizona State University · USCase Western Reserve University · USUniversity of Arizona · USUniversity of Kentucky · US

Funding

Role of PDE2A in mitochondrial dysfunction in Alzheimer’s diseaseR01AG070873 · NIA · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI XU, YING, ZHU, XIONGWEI · 2021 to 2025
$3.8M
Discovery of PDE2A inhibitors to treat memory deficits in mild cognitive impairment and Alzheimer's diseaseR43AG071045 · NIA · FD NEUROTECHNOLOGIES CONSULTING & SERVICES, INC. · PI DU, FU, O'DONNELL, JAMES M · 2021 to 2021
$500k
NIA NIH HHS R01 AG070873NIA NIH HHS R01 AG070873-01A1NIA NIH HHS R43 AG071045
6 · The paper itself

Abstract

backgroundPhosphodiesterase 2A (PDE2A) represents a novel target for new therapies addressing psychiatric disorders. To date, the development of PDE2A inhibitors suitable for human clinical evaluation has been hampered by the poor brain accessibility and metabolic stability of the available compounds.

methodsCorticosterone (CORT)-induced neuronal cell lesion and restraint stress mouse model were used to measure the neuroprotective effect in cells and antidepressant-like behavior in mice.

resultsThe cell-based assay showed that both Hcyb1 and PF were potent in protecting cells against stress hormone CORT insults by stimulating cAMP and cGMP signaling in hippocampal cells (HT-22). Administration of both compounds before treatment of CORT to cells increased cAMP/cGMP, VASP phosphorylation at Ser239 and Ser157, cAMP response element binding protein phosphorylation at Ser133, and brain derived neurotrophic factor BDNF expression. Further in vivo study showed that both Hcyb1 and PF displayed -antidepressant- and anxiolytic-like effects against restraint stress as indicated by reduced immobility time in the forced swimming and tail suspension tasks as well as increased open arm entries and time spent in open arms and holes visit in elevated plus maze and hole-board tests, respectively. The biochemical study confirmed that these antidepressant- and anxiolytic-like effects of Hcyb1 and PF were related to cAMP and cGMP signaling in the hippocampus.

conclusionsThe results extend the previous studies and validate that PDE2A is a tractable target for drug development in the treatment of emotional disorders such as depression and anxiety.

Indexed as

Anti-Anxiety AgentsPhosphodiesterase InhibitorsAnimalsAntidepressive AgentsAnxietyBehavior, AnimalBrain-Derived Neurotrophic FactorDepressionDisease Models, AnimalHippocampusHumansMicePhosphoric Diester HydrolasesAnti-Anxiety AgentsAntidepressive AgentsBrain-Derived Neurotrophic FactorPhosphodiesterase InhibitorsPhosphoric Diester Hydrolasesanxiety- and depression-like behaviorcGMP/cAMPHcyb1PDE2APF-05180999stress

Identifiers

PMID37208298
PMCPMC10289143
OpenAlexW4377116105

What OpenQuestion holds

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LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.