Effect of age onset on schizophrenia-like phenotypes and underlying mechanisms in model mice

Ju, Jun; Liu, Luping; Zhang, Yujie; Zhou, Qiang

doi:10.1016/j.pnpbp.2018.07.015

Cited by 8 publications

(15 citation statements)

References 79 publications

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“…Previous studies showed that injection of anti- Nrg1 antibodies led to the appearance of schizophrenia-like phenotypes in mice [49, 50], which is likely caused by elevated Nrg1 signaling [50]. In addition, enhanced synaptic transmission onto excitatory neurons was also seen in the anti-Nrg1 mice [49], consistent with other reports of hyperactivity in mice with NMDAR hypofunction in the inhibitory neurons [2]. Thus, we first examined in vivo cortical activity in the anti-Nrg1 mice.…”

Section: Resultsmentioning

confidence: 99%

“…Previous works showed that administration of anti-Nrg1 antibodies induced schizophrenia-like behavioral phenotypes (including hyper-locomotion and impaired pre-pulse inhibition of startle) and altered synaptic transmission in adult mice [49, 50]. Compared to the more established models of schizophrenia in the literature, being genetic, pharmacological or lesion, our model of using anti-Nrg1 antibodies is fairly new and less established, regarding the characterization of behavioral phenotypes, pathophysiology, responses to drugs/treatment (such as antipsychotics) and the developmental time course of the landmark events.…”

Section: Discussionmentioning

confidence: 99%

“…All animal experiments were performed in accordance with the ARRIVE guidelines on the Care and Use of Experimental Animals, approved by the Peking University Shenzhen Graduate School Animal Care and Use Committee. To establish a schizophrenia-like model, anti-Nrg1 antibody (a gift from Genentech) was intraperitoneally injected into 8 weeks old male mice (20 mg/kg,) three times within a 2 week period, while control mice were intraperitoneally administered with anti-Ragweed (anti-Rag) (20 mg/kg) [49, 50] . Mice were randomly divided into the two groups.…”

Section: Methodsmentioning

confidence: 99%

“…Measurement of locomotion was based on method described previously [49]. In brief, mice were placed in the testing room for 1–2 h to be familiar with the environment prior to testing.…”

Section: Methodsmentioning

confidence: 99%

“…NRG1 signaling could be mediated via canonical and non-canonical pathways, with the former requires NRG1 binding to ErbB4 receptor, and the latter not [44]. We used an anti-Neuregulin1 (anti-Nrg1) antibody to induce schizophrenia-like phenotypes, including hyperlocomotion and impaired prepulse inhibition [49, 50]. Injection of this antibody stabilized the full length Nrg1 and caused it to accumulate, based on in vitro evidence of robust increase of full length NRG1 in Nrg1-expressing 293 cells treated with anti-NRG1 antibodies.…”

Section: Introductionmentioning

confidence: 99%

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The impact of D-cycloserine and sarcosine on in vivo frontal neural activity in a schizophrenia-like model

et al. 2019

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BackgroundN-methyl-D-aspartate receptor (NMDAR) hypofunction has been proposed to underlie the pathogenesis of schizophrenia. Specifically, reduced function of NMDARs leads to altered balance between excitation and inhibition which further drives neural network malfunctions. Clinical studies suggested that NMDAR modulators (glycine, D-serine, D-cycloserine and glycine transporter inhibitors) may be beneficial in treating schizophrenia patients. Preclinical evidence also suggested that these NMDAR modulators may enhance synaptic NMDAR function and synaptic plasticity in brain slices. However, an important issue that has not been addressed is whether these NMDAR modulators modulate neural activity/spiking in vivo.MethodsBy using in vivo calcium imaging and single unit recording, we tested the effect of D-cycloserine, sarcosine (glycine transporter 1 inhibitor) and glycine, on schizophrenia-like model mice.ResultsIn vivo neural activity is significantly higher in the schizophrenia-like model mice, compared to control mice. D-cycloserine and sarcosine showed no significant effect on neural activity in the schizophrenia-like model mice. Glycine induced a large reduction in movement in home cage and reduced in vivo brain activity in control mice which prevented further analysis of its effect in schizophrenia-like model mice.ConclusionsWe conclude that there is no significant impact of the tested NMDAR modulators on neural spiking in the schizophrenia-like model mice.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…Measurement of locomotion was based on method described previously [49]. In brief, mice were placed in the testing room for 1–2 h to be familiar with the environment prior to testing.…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The impact of D-cycloserine and sarcosine on in vivo frontal neural activity in a schizophrenia-like model

et al. 2019

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Interaction of emotion and cognitive control along the psychosis continuum: A critical review

Duggirala

Schwartze

Pinheiro

et al. 2020

International Journal of Psychophysiology

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People interested in the research are advised to contact the author for the final version of the publication, or visit the DOI to the publisher's website.• The final author version and the galley proof are versions of the publication after peer review.• The final published version features the final layout of the paper including the volume, issue and page numbers. Link to publication General rightsCopyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal.If the publication is distributed under the terms of Article 25fa of the Dutch Copyright Act, indicated by the "Taverne" license above, please follow below link for the End User Agreement:

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Adenosine mediates the amelioration of social novelty deficits during rhythmic light treatment of 16p11.2 deletion female mice

Ju,

Li,

Pan

et al. 2024

Mol Psychiatry

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Non-invasive brain stimulation therapy for autism spectrum disorder (ASD) has shown beneficial effects. Recently, we and others demonstrated that visual sensory stimulation using rhythmic 40 Hz light flicker effectively improved cognitive deficits in mouse models of Alzheimer’s disease and stroke. However, whether rhythmic visual 40 Hz light flicker stimulation can ameliorate behavioral deficits in ASD remains unknown. Here, we show that 16p11.2 deletion female mice exhibit a strong social novelty deficit, which was ameliorated by treatment with a long-term 40 Hz light stimulation. The elevated power of local-field potential (LFP) in the prefrontal cortex (PFC) of 16p11.2 deletion female mice was also effectively reduced by 40 Hz light treatment. Importantly, the 40 Hz light flicker reversed the excessive excitatory neurotransmission of PFC pyramidal neurons without altering the firing rate and the number of resident PFC neurons. Mechanistically, 40 Hz light flicker evoked adenosine release in the PFC to modulate excessive excitatory neurotransmission of 16p11.2 deletion female mice. Elevated adenosine functioned through its cognate A1 receptor (A1R) to suppress excessive excitatory neurotransmission and to alleviate social novelty deficits. Indeed, either blocking the A1R using a specific antagonist DPCPX or knocking down the A1R in the PFC using a shRNA completely ablated the beneficial effects of 40 Hz light flicker. Thus, this study identified adenosine as a novel neurochemical mediator for ameliorating social novelty deficit by reducing excitatory neurotransmission during 40 Hz light flicker treatment. The 40 Hz light stimulation warrants further development as a non-invasive ASD therapeutics.

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Effect of age onset on schizophrenia-like phenotypes and underlying mechanisms in model mice

Cited by 8 publications

References 79 publications

The impact of D-cycloserine and sarcosine on in vivo frontal neural activity in a schizophrenia-like model

The impact of D-cycloserine and sarcosine on in vivo frontal neural activity in a schizophrenia-like model

Interaction of emotion and cognitive control along the psychosis continuum: A critical review

Adenosine mediates the amelioration of social novelty deficits during rhythmic light treatment of 16p11.2 deletion female mice

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