Persistent gating deficit and increased sensitivity to NMDA receptor antagonism after puberty in a new mouse model of the human 22q11.2 microdeletion syndrome: a study in male mice

AbstractBackgroundExperiencing early-life stress plays an important role in the pathophysiology of anxiety disorders. Ferulic acid is a phenolic compound found in some plants which has several pharmacological properties. N-methyl-D-aspartate (NMDA) receptors are involved in the pathophysiology of mood disorders. In this study we aimed to assess the anxiolytic-like effect of ferulic acid in a mouse model of maternal separation (MS) stress by focusing on the possible involvement of NMDA receptors.MethodsMice were treated with ferulic acid (5 and 40 mg/kg) alone and in combination with NMDA receptor agonist/antagonist. Valid behavioral tests were performed, including open field test (OFT) and elevated plus maze test (EPM), while quantitative real time polymerase chain reaction (qRT-PCR) was used to evaluate gene expression of NMDA subunits (GluN2A and GluN2B) in the hippocampus.ResultsFindings showed that treatment of MS mice with ferulic acid increased the time spent in the central zone of the OFT and increased both open arm time and the percent of open arm entries in the EPM. Ferulic acid reduced the expression of NMDA receptor subunit genes. We showed that administration of NMDA receptor agonist (NMDA) and antagonist (ketamine) exerted anxiogenic and anxiolytic-like effects, correspondingly. Results showed that co-administration of a sub-effective dose of ferulic acid plus ketamine potentiated the anxiolytic-like effect of ferulic acid. Furthermore, co-administration of an effective dose of ferulic acid plus NMDA receptor agonist (NMDA) attenuated the anxiolytic-like effect of ferulic acid.ConclusionsIn deduction, our findings showed that NMDA, partially at least, is involved in the anxiolytic-like effect of ferulic acid in the OFT and EPM tests.

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The Importance of Having Arc: Expression of the Immediate-Early Gene Arc Is Required for Hippocampus-Dependent Fear Conditioning and Blocked by NMDA Receptor Antagonism

Journal of Neuroscience ◽

10.1523/jneurosci.2211-11.2011 ◽

2011 ◽

Vol 31 (31) ◽

pp. 11200-11207 ◽

Cited By ~ 61

Author(s):

J. Czerniawski ◽

F. Ree ◽

C. Chia ◽

K. Ramamoorthi ◽

Y. Kumata ◽

...

Keyword(s):

Nmda Receptor ◽

Fear Conditioning ◽

Immediate Early Gene ◽

Early Gene ◽

Immediate Early ◽

Receptor Antagonism

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Animal models of cognitive dysfunction and negative symptoms of schizophrenia: Focus on NMDA receptor antagonism

Pharmacology & Therapeutics ◽

10.1016/j.pharmthera.2010.07.004 ◽

2010 ◽

Vol 128 (3) ◽

pp. 419-432 ◽

Cited By ~ 339

Author(s):

Joanna C. Neill ◽

Samuel Barnes ◽

Samantha Cook ◽

Ben Grayson ◽

Nagi F. Idris ◽

...

Keyword(s):

Nmda Receptor ◽

Animal Models ◽

Cognitive Dysfunction ◽

Negative Symptoms ◽

Receptor Antagonism

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Estrogen and NMDA receptor antagonism: effects upon reference and working memory

European Journal of Pharmacology ◽

10.1016/s0014-2999(99)00583-x ◽

1999 ◽

Vol 381 (2-3) ◽

pp. 93-99 ◽

Cited By ~ 54

Author(s):

Iain A Wilson ◽

Jukka Puoliväli ◽

Taneli Heikkinen ◽

Paavo Riekkinen

Keyword(s):

Working Memory ◽

Nmda Receptor ◽

Receptor Antagonism

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Abstract 620: Development Of A New Mouse Model Exhibiting A Specific Deficiency Of Prorenin Renin Receptor In Adipocytes.

Hypertension ◽

10.1161/hyp.64.suppl_1.620 ◽

2014 ◽

Vol 64 (suppl_1) ◽

Author(s):

Frederique B Yiannikouris ◽

Genevieve Nguyen

Keyword(s):

Blood Pressure ◽

Adipose Tissue ◽

Mouse Model ◽

Preliminary Data ◽

The Body ◽

Chow Diet ◽

Slight Reduction ◽

Male Mice ◽

Exon 2 ◽

Adipose Tissue Stromal Cells

Objectives: Recent studies demonstrated that the prorenin renin receptor (PRR) is present in adipose tissue. In adipose tissue stromal cells, PRR has the ability to bind renin and prorenin and contributes to the generation of angiotensinI (AngI). However, the contribution of adipocyte PRR to the generation of the vasoactive peptide, AngII and therefore to the regulation of blood pressure in physiological condition is unknown. The purpose of this study was to develop and characterize a new mouse model with adipocyte-specific PRR deficiency and define the role of adipose PRR in normal physiology. Methods and results: Female mice with 2 loxP sites flanking exon 2 of the PRR gene (floxed alleles, PRRfl/fl) were bred with aP2-Cre or with Adi-Cre male mice. Since PRR is located in the X chromosome, the male mice generated from the breeding were homozygotes for the deletion (PRRaP2 and PRRAdi). From the breeding, 5 PRRfl/fl, 2 PRRaP2 and 5 PRRAdi male mice were generated suggesting that the deletion of PRR in adipocyte was not lethal. Mice were fed on chow diet during 20 weeks. The body weight, the fat, lean mass and the blood pressure were quantified. Preliminary data suggest that the body weights (BW) were slightly decreased in PRRaP2 and PRRAdi compared to PRRfl/fl (PRRfl/fl: 29±1g; PRRaP2: 25±5g; PRRAdi: 28±1g). The slight reduction in BW was attributed to a reduction in fat mass (PRRfl/fl: 4.8±0.9g; PRRaP2: 3.8±1.8g; PRRAdi: 1.9±0.4g). Blood pressure was measured by plethysmography and by radiotelemetry. Preliminary data demonstrated that under physiological conditions, the SBP was not changed in PRRaP2 male mice compared to PRRfl/fl mice (plethysmography: PRRfl/fl: 108±1 mmHg; PRRaP2: 99±7 mmHg; radiotelemetry: PRRfl/fl: 129±2 mmHg; PRRaP2: 128±6 mmHg). The SBP of PRRAdi is currently under investigation. Conclusions: These results demonstrate the viability of mice with specific adipocyte deficiency of PRR. Future studies will define the effects of adipocyte PRR deficiency on obesity-induced hypertension.

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